Registered studies, protocols and reported results
Studies
Clinical study protocols and source-reported registry results, preserved locally.
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Registered studies, protocols and reported results
Clinical study protocols and source-reported registry results, preserved locally.
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Registered studies, protocols and reported results
Study registrations describe protocols. Results are shown only when the registry supplied a Results section; local links are not efficacy claims.
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Snapshot 14/09/2026Inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis, are chronic, relapsing conditions characterized by persistent inflammation of the gastrointestinal tract and a significant impact on patients' quality of life. Crohn's disease can involve any part of the gastrointestinal tract, most commonly the terminal ileum and colon, whereas ulcerative colitis is confined to the colonic mucosa. Typical symptoms include abdominal pain, diarrhea, fatigue, fever, and weight loss, often alternating between periods of remission and disease flare-ups.In addition to intestinal involvement, IBD are frequently associated with extraintestinal manifestations affecting multiple organ systems. Among these, enteropathic arthritis represents one of the most common and clinically relevant complications. It belongs to the spectrum of spondyloarthritis, a group of inflammatory joint disorders characterized by axial and/or peripheral involvement, enthesitis, and dactylitis. Enteropathic arthritis is reported in a substantial proportion of IBD patients and may occur independently of intestinal disease activity. Although its pathogenesis is not fully understood, current evidence suggests a multifactorial mechanism involving gut microbiota dysbiosis, immune dysregulation with expansion of Th17 cells, and migration of activated immune cells to the joints in genetically predisposed individuals.Management of musculoskeletal manifestations in IBD remains challenging. Conventional therapeutic strategies are primarily aimed at controlling intestinal inflammation and often fail to adequately address joint pain. Escalation of immunomodulatory or biologic therapies may be required when articular symptoms parallel intestinal flares; however, persistent pain can occur even during disease remission, potentially due to nociplastic or neuropathic mechanisms or degenerative joint disease. The long-term use of analgesic and anti-inflammatory medications, including COX-2 inhibitors, antidepressants, anticonvulsants, opioids, and cannabis, is associated with relevant adverse effects and may worsen gastrointestinal symptoms.Given these limitations, non-pharmacological and complementary approaches are gaining interest. Nutraceutical interventions have shown promising results in alleviating musculoskeletal symptoms while minimizing gastrointestinal toxicity. GenesiDol, a nutrigenomic dietary supplement containing palmitoylethanolamide, avocado/soy extracts, probiotics, antioxidants, and neuroprotective compounds, represents a potential supportive strategy for the management of chronic musculoskeletal pain in patients with IBD.
Cannabis, in addition to its psychotropic properties, could have anti-inflammatory and immunomodulatory effects. Phytocannabinoids (pCBs) are a group of molecules naturally secreted by the cannabis plant. The major pCBs are cannabidiol (CBD) and Δ9-tetrahydrocannabinol Δ9 (THC). Only THC has psychotropic effects, which CBD does not have. Alongside these two main components, there is a wide variety of other molecules, such as other pCBs and terpenes which could increase the effects on immune system through synergistic interactions between these different compounds ("entourage effect").In vivo, pCBs essentially interfere with the endocannabinoid system, acting on many ubiquitous receptors, present on a significant number of different cell types. Numerous published studies show that pCBs have immunomodulatory and anti-inflammatory properties by acting on several of these receptors, whether through modulation of the immune response of different cell types, effects on cytokine networks, reduction of innate and adaptive responses and/or impact on cell survival or death (autophagy, proliferation/ apoptosis). The Immune-Mediated Inflammatory Diseases (IMIDs) affect 5 to 7% of the general population in Western countries, involve different organs (joints, skin, digestive tract) but share the same inflammatory mechanisms resulting from a dysregulation of the immune response. Our research focuses on the identification of the most effective phytochemical profile of pCBs, allowing an optimal effect on chronic inflammatory pathologies of interest among immune-mediated chronic inflammatory diseases (IMIDs). The pCB-IMIDs project is therefore part of an innovative translational project, around new therapeutic applications of medical cannabis (CannAppIMIDs). In our study, we will include 100 patients with one of IMIDs among Rheumatoid Arthritis, spondylarthritis, psoriatic arthritis, Sjogren disease and systemic lupus, at different stage and with different treatments. After patient's consent we will collect for research purposes an additional 40 ml of blood during a routine care blood test. Mononuclear and polynucleated blood cells will be exposed in vitro to different full-spectrum pCB extracts (full spectrum extract) including a CBD dominant and low THC extract (\<0.2%), 1 dominant THC extract, 1 balanced THC/CBD extract and 1 dominant CBG extract. In this cross-sectional study, our objective will be to assess the biological effects of different pCB compositions on inflammatory profiles (concentrations of pro and anti-inflammatory cytokines and chemokines) and modulations of expression profiles (autophagy, apoptosis, and cannabinoid receptor expression profile). Background: The analgesic and anxiolytic properties of cannabis are at the origin of the French experiment on medical cannabis set up in 2020 and led by the ANSM (National Agency for the Safety of Medicines and Health Products) for 5 well-identified pathologies (neuropathic pain, certain forms of pediatric epilepsy, symptoms linked to cancer or anti-cancer treatment, palliative situations and painful spasticity linked to multiple sclerosis). Phytocannabinoids (pCBs) are a group of molecules naturally secreted by the cannabis plant. The main pCBs are cannabidiol (CBD) and Δ9-tetrahydrocannabinol Δ9-THC \[1, 2\]. Only THC has psychotropic effects, which CBD does not have. Alongside these two main components, there is a wide variety of molecules \[cannabigerol (CBG), cannabinol (CBN), cannabichromene (CBC) and other terpenes\] which are said to have an "entourage effect" by increasing the effects by synergistic interactions between these different compounds \[3-7\]. CBD of natural origin can be purified without other terpenes corresponding to CBD alone ("CBD isolate") or is combined with terpenes and phytocannabinoids but without THC or any other pCB ("broad spectrum"), or in unpurified form, CBD with terpenes and THC ("full spectrum"). In vivo, pCBs essentially interfere with the endocannabinoid system, acting on numerous receptors present on a large number of different cell types \[8\]. This means that pCBs can be used to treat a wide range of organs. Numerous published works show that pCBs have immunomodulatory and anti-inflammatory properties by acting on several of these receptors, whether via modulation of the immune response of different cell types, effects on cytokine networks, reduction of innate and adaptive responses \[9, 10\] and/or impact on cell survival or death (autophagy, proliferation/apoptosis) \[8, 9\]. Thus, in addition to its neurological effects \[10, 11\], cannabis possesses anti-inflammatory, pro-autophagic and anti-proliferative properties, which are still imperfectly characterized. Understanding the mechanisms of action of pCBs, individually or in combination with other molecules present in cannabis, on different therapeutic targets therefore presents an immense challenge in the management of Immune-Mediated Inflammatory Diseases (IMIDs). These IMIDs affect 5 to 7% of the general population in Western countries, and involve different organs (joints, skin, gut) but share the same inflammatory mechanisms, resulting from a deregulation of the immune response. The pCB-IMIDs project is part of an innovative translational project focusing on new therapeutic applications for medical cannabis (CannAppIMIDs). Objectives: The objective of this exploratory project is to evaluate the biological and immunological effects of exposure of blood cells from patients suffering from IMID to different varieties of pCB extracts on: 1. The inflammatory profile (main objective) 2. The expression profile of cannabinoid receptors 3. The autophagic and apoptotic profile Methods: Single-center cross-sectional study without prospective follow-up of participants, classified non-interventional study. The study consists, after obtaining consent and verifying the eligibility criteria (with saliva test specific to the study), in taking an additional 40 ml of blood during a planned blood test for research purposes and to collect medical data on patients and their inflammatory pathology. Mononuclear and polynuclear blood cells from subjects suffering from IMID will be exposed in vitro to different inflammatory inducers used individually and/ or all together (LPS- bacterial Lipopolysaccahride, TLR-4 ligand and/or poly-I:C , TLR-3 ligand and/or PAM3CSK4, TLR1/TLR2 ligand, and/or PHA-P - phytohemagglutin P, polysaccharide and glycoprotein ligand) with and without the concomitant addition of different complete spectrum of pCB extracts (full spectrum) including a dominant CBD extract and low in THC (\<0.2%), 1 dominant THC extract, 1 balanced THC/CBD extract and 1 dominant CBG extract. The same analyzes will be carried out in the presence of a recognized anti-inflammatory (for example hydrocortisone or dexamethasone) which will thus serve as a positive control \[12\]. All analyses will be carried out at CBM - UPR4301 CNRS. Results will allow us to formulate hypotheses, guide and argue for future clinical research studies evaluating the benefit(s) and tolerance of extracts rich in pCB in taking in therapeutic management of IMIDs.
Open study recordNewborn screening (NBS) is a global initiative of systematic testing at birth to identify babies with pre-defined severe but treatable conditions. With a simple blood test, rare genetic conditions can be easily detected, and the early start of transformative treatment will help avoid severe disabilities and increase the quality of life. Baby Detect Project is an innovative NBS program using a panel of target sequencing that aims to identify 126 treatable severe early onset genetic diseases at birth caused by 361 genes. The list of diseases has been established in close collaboration with the Paediatricians of the University Hospital in Liege. The investigators use dedicated dried blood spots collected between the first day and 28 days of life of babies, after a consent sign by parents. Every year, thousands of children around the world are born with rare genetic diseases leading to death or lifelong disability. With technological advancements in the field of genetics and medicine, the rate of introduction of treatments for these rare conditions has grown remarkably. However, timing is of great importance for medication administration. The benefit that can be measured in a patient who has already suffered from a long irreversible degenerative disorder is small and, sometimes, it hardly justifies the cost and the burden of the treatment. Early diagnosis is, thus, of primary importance both to obtain the best effect of the innovative medications and to accelerate their development. The investigators are pioneered in the field of genetic newborn screening (NBS) in rare diseases by funding, designing, and leading an innovative genetic NBS program initiated in March 2018 in Southern Belgium for Spinal Muscular Atrophy (SMA) that allowed, so far, for 11 children to be detected and treated early and avoid the terrible fate of the disease. The program was disseminated in 17 countries and included public dissemination and health-economic analysis since the very beginning \[1\]. (www.facebook.com/sunmayariseonsma). Drawing upon our experience with SMA screening, the investigators have designed a project to screen up to 40,000 newborns/year progressively in 3 years for virtually all the rare diseases that can benefit from treatment or a pre-symptomatic clinical trial. The methodology of Baby Detect includes sequencing of target genes on dried blood spots collected from the NBS cards in a timely and cost-efficient manner, and its high dynamicity allows for any newly treatable rare disease to be included in its scheme in no longer than 6 months. Baby Detect, as a multidisciplinary newborn screening program, involves expertise in areas from genetics and medicine to laboratory studies, computer science, Data Protection, Ethics, and health economy. It will constitute the proof of concept that is needed before moving to a whole region-scale population.
Open study recordThe purpose of this study is to investigate the effects of Samyama program on blood levels of selected neurotransmitters before and after the program, and associate with corresponding effects on mind/psyche before and after the program in adult participants. Hypothesis: 1. The state of higher consciousness and ecstasy resulting from Samyama result from increased levels of Anandamide, an endocannabinoid, and Brain Derived Neurotrophic Factor (BDNF). 2. The 60-day preparatory phase that includes dietary regulation and yogic practices will reduce the gut inflammation and thereby will improve the gut microbiome. Potential participants (those signed up to attend the Samyama program at Isha) will be sent email invitations approximately 2 months prior to the program. Participants will have the options to take part in online surveys, blood samples, and/or stool samples. Up to 1000 participants (attendees and spouses/significant others) may take the online surveys twice before the samyama program, 2 weeks after and 3 months after. Up to \*200 may volunteer to have 4 blood draws. (Blood draws will occur 1. At home, or at an Isha group meditation, 1-2 months prior to Samyama 2. At Isha before the start of the program 3. At Isha after the program 4. At home after returning from the Samyama program). 150 volunteers may also send in 3 stool samples - 1. prior to starting the Samyama pre-prep diet 2. within one week of the Samyama program 3. After returning home from the program. Up to 50 spouses/significant others living with Samyama attendees will also be offered the opportunity to complete a shortened version of the online surveys, provide (2) blood and/or (3) stool samples. Blood would be collected at home prior to their spouses/significant other's Samyama attendance and in their home after the program. Requested stool samples would be asked to be collected approximately 1 month prior to the program, 1 week prior to the program and one week after the program. Blood samples will be sent to Indiana University and may be sent to other specialty labs for additional analysis. Genetic and future biomarker samples will be stored at the PI's Indiana University lab facilities. If survey participants do not complete surveys during suggested time periods, they may also be sent reminders (via emails) to complete surveys. \*Only up to 150 volunteers will have at home blood draws (or blood draws at an Isha group meditation). Only those who participated in the pre-Samyama at home blood draws will be asked to participate in the post-Samyama blood draws. Up to 200 volunteers at Isha can participate in blood draws (regardless of whether they participated in at home blood draw). Those who complete the survey will also be asked if they have a significant other or spouse who lives with them who would be willing to complete surveys, and participate in blood draws and/or provide stool samples. Participants with willing spouses will be asked to enter an email address for that spouse/significant other. Spouse/significant other will be emailed the invitation with study information. Upto 25 subjects will also be enrolled in the (2)EEG and (2)fMRI Study March 19 and March 29, 2018 (before Samyama), and between April 9th and May 9th, 2018 (after Samyama).
Open study recordActivSightTM combines an innovative form factor and proprietary software to deliver precise, objective, real-time visualization of blood flow and tissue perfusion intraoperatively for laparoscope-based surgery. A small adaptor that fits between any existing laparoscope and camera systems and a separate light source placed along any current commercial system will deliver objective real-time tissue perfusion and blood flow information intraoperatively. Primary Objective: To determine safety and feasibility of ActivSightTM in displaying tissue perfusion in intestinal anastomoses including colorectal and bariatric surgery. Secondary Objective: To determine the efficacy of ActivSightTM in; (1) displaying tissue vascularity and perfusion in comparison to indocyanine green (ICG) during gastrointestinal anastomoses; and (2) displaying biliary tree during laparoscopic cholecystectomy using ICG-based intraoperative cholangiography (IOC). Design: * This is a feasibility study designed to evaluate safety and feasibility of ActivSightTM in gastrointestinal anastomoses and cholecystectomy. * Safety will be determined through clinical assessments and evaluation of any adverse event. * Feasibility will be determined through technically successful completion of intended visualization. * Assessment of preliminary efficacy will be performed through analysis of any intraoperative decisions made based on visual display as compared to standard endoscopic approach, or non-inferiority to ICG-based visualization and usability. * Patients outcome and follow up to Postoperative day 28 will be monitored for clinical outcome. * Target enrollment for the assessment of 80 patients; 52 evaluating intestinal anastomoses cases (including bariatric and colorectal cases); and 28 evaluating laparoscopic cholecystectomy. Stopping rules are triggered following the first 6 patients and a comparison group 6 patients in ICG-based treatment.
Open study recordThis is a clinical trial of nabilone for patients with Inflammatory Bowel Disease (IBD) who are undergoing IBD-related surgery (Any abdominal surgery lasting for more than one hour). This study would include a total of 80 patients undergoing general surgery who will have Intravenous Patient Controlled Analgesia (IVPCA) after surgery. It is the intention to randomize these patients postoperatively into 2 groups of 40 patients: 1. Patients who are chronic opioid users for chronic pain and have been exposed to cannabis or cannabinoid products, treated with IV PCA and nabilone as per protocol. 2. Patients who are chronic opioid users for chronic pain and have been exposed to cannabis or cannabinoid products, treated with IV PCA and placebo as per protocol. The goal is two-fold. One is to demonstrate that patients will benefit from post-operative nabilone administration to achieve/maintain the opioid-sparing and pain modulation effects. Second is to demonstrate patients will benefit from the anti-inflammatory and immunomodulatory effects of nabilone to alleviate IBD symptoms and enhance recovery. Patients generally have pre-anesthetic visits 1-2 weeks prior to their scheduled operation. Patients identified by the Clinical Research Study Assistant (CRSA) based on inclusion and exclusion criteria will be approached regarding this study in the pre-anesthetic clinic. Patients will be made aware of the components of the study and the CRSA will be present to answer any questions. Patients have until the day of the surgery after admission to the hospital (generally 4 hours before the planned procedure) to decide whether they want to be enrolled in this study. In most cases patients will have approximately 1-2 weeks from being made aware of this study to come to a decision. Even patients who have been scheduled for pre-anesthetic clinic visit less than 1 week prior to surgery will still have \>24 hrs to make decisions. Those admitted on the day of surgery may still be able to participate provided they have at least 4 hrs to review the study and have their questions answered by the study team. Patients will have access to a contact phone number in case they have additional questions. Baseline patient data will be collected once consent is obtained. On the day of surgery, administration of general anesthesia (GA) will be protocolized. Patients will cease their current oral opioid while on IV opioids. After the surgery, Patients will be randomly allocated into either placebo or intervention arm using a computerized random generator. Treatment regimen will involve nabilone capsule administration starting with 1mg twice a day orally first administered on post-operative day (POD) #0. The patient will be continued on this medication for 72 hours. Enrolled patients will document their pain scores and other data points as per study outcomes measured. The CRSA will follow for nabilone-related adverse effects at 24hrs, 48hrs, and 72hours post-operatively. Study subjects will also be followed up for psychotropic adverse reactions of nabilone (including hallucination, depressed mood, anxiety reactions, and euphoria) for 3 days after discontinuation of study treatment. This follow up will be made by the CRSA during the subject's stay in the hospital, or by telephone call made after discharge from the hospital. Any surgical complication will be recorded up to 30 days after the operation. The CRSA will administer study questionnaires and assist patients in their completion. The CRSA will work with the principal investigator (PI) to capture all requirements for study evaluation.
Open study recordThe inflammatory bowel diseases (IBDs), ulcerative colitis (UC) and Crohn's disease (CD), are characterized by lifelong relapsing-remitting gastrointestinal inflammation, with symptoms of abdominal pain, diarrhea, and rectal bleeding during active disease. Medical therapy reduces intestinal inflammation and ameliorates symptoms. Medical cannabis has recently been added to the arsenal of symptom-reducing measures in IBD. Though the efficacy of THC and CBD have been established as the two most dominant ingredients of cannabis, the rest of the plant phytochemicals are unknown, and effects on patients are not yet determined. Hypothesis (es) and Aims: Prospectively follow IBD patients receiving medical cannabis as treatment of their disease (group 1) in comparison to the following control groups: 2\) Healthy patients who do not use cannabis; 3) IBD patients who experience pain and do not use cannabis; 4) IBD patients who do not experience pain and do not use cannabis; 5) IBD patients previously prescribed cannabis and were identified to have positive effect on their disease • Specific aims: a prospective trial to determine whether cannabis can induce remission in patients with IBD. * To identify treatment regimens associated with treatment success in IBD patients. * To identify treatment regimens associated with treatment side effects in IBD patients. * To analyze the optimal drug level for disease management in various IBD patient types. * Study design: * A prospective cohort study * Setting: prospectively collect clinical, behavioral, dietary and environmental data of IBD patients receiving medical cannabis as treatment of their disease. Data will be collected according to a uniform standardized protocol specifically adapted to the needs of the study. * Study population: Eligible IBD patients treated at the IBD clinic in the Tel Aviv Medical Center participating in the study, which have signed an informed consent form and answered to all the study inclusion criteria. Patients will be informed of the study by their treating physician, recruited and followed throughout the follow-up period by study coordinators. This study will include five patient groups: * Group 1 (study group): IBD patients prescribed cannabis as treatment for their bowel disease. * Group 2 (Control group): One hundred healthy patients who do not use cannabis and are not eligible or not interested to commence this intervention. * Group 3 (control group): Up to 100 IBD patient who experience pain and do not use cannabis * Group 4 (control group): Up to 100 IBD patient who do not experience pain and do not use cannabis * Group 5 (Cannabis responders group): up to 100 IBD patients previously prescribed cannabis and were identified to have positive effect on their disease \*Study plan: * Among the study group : At baseline, demographic characteristics, medical history, concomitant medication assessment, disease related therapy and failed therapy will be documented. Study visits: Among the study group: recruitment at time 0, after one month (±14 days) of treatment, at three months (±21 days) and at 6 months (±30 days) of therapy (end of study), will be conducted, in which patients will be asked to fill in questionnaires, give biologic samples, undergo clinical, anthropometric and nutritional evaluation and physician assessment and monitoring of therapy, safety and adverse events. The cannabis producing company, composition, quantity and way of consumption will be documented. •Among control group and Cannabis responders group: Healthy controls will be samples once at baseline. All IBD control groups (groups 3-5) will be followed up similarly as the study group and will undergo all sampling and questionnaires, at times 0, 3, 6 months (excluding the 1 month cannabis dose adjustment meeting). Patients will be asked to inform in case of relapse during the follow up period and provide stool and blood samples before therapy is changed. At relapse time point, disease activity index will be recorded and questionnaires will be completed. \*Sample collection: Baseline and follow up study visits will include biologic samples collection (blood, feces) from which blood levels of complete blood count (CBC), Albumin, Liver enzymes (ALT, AST, ALP), lipid panel (Total cholesterol, LDL, HDL, triglycerides), creatinine, fasting glucose, C-reactive protein (CRP), drug levels and antibodies (for patients treated with thiopurines and biologics), and fecal levels of Calprotectin will be measured. White blood cells will be separated and stored for m RNA analysis of cannabinoid metabolism. Only RNA fractions will be extracted and analyzed, no DNA will be assessed and no genetic sequencing will be performed . In addition, 10 ml of blood will be drawn for analysis of Th17 cells. CD4 T cells will be purified from peripheral blood of IBD patients by RosetteSep™ Human CD4+ T Cell Enrichment Cocktail kit. STAT3 and IL-17 levels will be analyzed. The samples analysis will be done at Dedi Meiri's lab at the Technion-IIT. Serum, and fecal samples will be stored at -80◦C for future analysis after being authorized by the IRB and by law including cannabis phytochemical analysis (10ml of each) on WBC and on biopsies when available and for fecal microbiome analysis. In appendix A- a detailed list of all tests in each visit. \*Endoscopic evaluation: In patients who will undergo a standard of care endoscopic examination for clinical reasons: these will include mucosal and histologic assessment for disease severity (SES-CD and MAYO score for CD and UC patients respectively, PDAI for Pouchitis patients). Mucosal biopsies will be collected from inflamed and healthy areas, and from standard areas of the GI track (table 1), sent for histology assessment and stored for future analysis after being authorized by the IRB and by law. These samples will be stored in RNA Later snapped frozen and stored at -80◦c until analysis. No more than 10 samples will be collected during endoscopy including samples for clinical assessment. Samples from recto-sigmoid junction (20 cm from anus) will be taken in every colonoscopy, regardless of the status of inflammation. \*Biologic sample handling: Samples will be stored at -80◦c while coded with no identifying information; access to samples will be restricted to the study staff only. Samples will be stored up to 10 years from final data collection. In this study, serum and fecal samples analyzed will include those gathered from protocol number 0276-19 and from protocol number 0250-17 in patients using medical cannabis only. In the later group, samples will be used only if the patient had agreed for use of samples in other studies other than 0250-17. To both studies, Professor Nitsan Maharshak is PI. \*Questionnaires: Baseline and follow up study visits will include data collection from the following: * Documentation of cannabis therapy: consumption method, quantity, THC/CBD concentration and cannabis strain/ barcode of preparation * Food frequency questionnaire * Food diary from last 3 days * Lifestyle questionnaire * Medical management questionnaire (IBD SES- self efficacy scale questionnaire) * Patient reported outcomes (PROMIS) questionnaires * Medical cannabis treatment evaluation questionnaire and Adverse events * Big Five personality traits Anthropometric and nutritional evaluation: * Patients weight (kg), height (m), waist circumference (cm) will be documented at each study visit, and body mass index (BMI) will be calculated. * Nutritional status will be evaluated by a MUST questionnaire \*Study endpoints: the study will follow patients throughout 6 months of treatment and follow disease remission (clinical/biochemical) or exacerbation. * Disease remission: * Reduction in appropriate clinical scores * Decrease in serum CRP or fecal CLP * Endoscopic remission * Disease exacerbation: * Increase in appropriate clinical score * Increase in fecal calprotectin levels (\>250mg/gr OR 100 units higher than baseline levels) * Emergency room visit due to disease symptoms, hospitalization, non-elective surgery. * Diagnosis of active disease by endoscopy or imaging * Medical treatment change by treating physician * Statistical analysis: Statistical analyses will be performed using SPSS version 23.0 for Windows. Patients who adhere to the study's protocol (defined as preforming ≥ 80% of exercises) will be included in data analysis. An intention-to-treat analysis will include patients excluded because of non-adherence to the intervention. Descriptive statistics will be used to describe the distribution of variables associated with characteristics of the study sample. Continuous variables will be presented as means± SD and dichotomous/categorical variables as proportions. The normality of the distribution of continuous variables will be tested by the Kolmogorov-Smirnov test. If normality is rejected, non-parametric tests will be used. Univariate analysis: To test the association between continuous variables with normal distribution, the Pearson correlation coefficient will be performed. To test associations between continuous variables which do not distribute normally or for ordinal variable, the spearman correlation coefficient will be used. To test differences in continuous variables between the treatments arms the t-test for independent groups (or Mann-Whitney test for non-normally distributed variables) will be performed. For comparison of dichotomous or categorical variables the Chi-square test will be performed. To compare baseline to end of treatment parameters within arms for continuous variables the t-test for dependent groups will be performed (or Wilcoxson test for non-normally distributed variables), in dichotomous/categorical variables the McNemar Test will be performed. To test differences in continuous variables between the treatment groups in numbers of time points the Mix model for repeated measures will be performed. To test differences in dichotomous/categorical variables between the treatment groups in numbers of time points Generalized estimating equation will be performed.
Open study recordCrohn's disease (CD) is a chronic disease with a heterogeneous clinical presentation, relapse rate and treatment response. Insufficient control of mucosal inflammation results in irreversible bowel damage and complications and at present no markers are available to predict such a complicated disease course at diagnosis. Therefore, to prevent overtreatment of low risk patients, step-up treatment with subsequent introduction of corticosteroids, thiopurines maintenance and TNF-blockers if a previous category fails is standard care. Combination treatment with thiopurines and a TNF-blocker is more effective than monotherapy but associated with a higher risk for infectious complications. Landmark studies convincingly showed an improved long-term outcome if the TNF-blocker infliximab is introduced early after diagnosis. The standard step-care approach thus prolongs steroid exposure and delays start of disease modifying biologicals in high risks patients. Given the higher efficacy of combination therapy with a thiopurine of infliximab and potential allergic reactions and lower response rates after re-initiation of this chimeric biological, temporary monotherapy with this TNF-blocker has not been studied as first line treatment before. Adalimumab is a humanised monoclonal antibody and subsequently, combination therapy of adalimumab + thiopurines has only a marginal effect on anti-drug anti-body formation. Furthermore, combination therapy with adalimumab does not enhance the clinical response. Therefore, periodic treatment with adalimumab in combination with close monitoring after drug-discontinuation, in newly diagnosed CD might improve outcome, reduce drug-related side effects while still preventing overtreatment. The aim of this study is to compare the long-term efficacy and safety of periodic adalimumab as initial treatment in newly diagnosed CD patients compared to standard step-care with corticosteroid/budesonide as the initial treatment
Open study recordThis will be a multistate, multicenter clinical study to determine the efficacy and safety of medical cannabis for a wide variety of chronic medical conditions. Medical cannabis has been legal in parts of the USA since 1996, with the stated intention of reducing pain (both acute and chronic) as well as for treatment of multiple other conditions. The original implementation of medical cannabis in the USA was implemented in California as a compassionate measure to treat the HIV/AIDS epidemic. Additional studies have shown promising outcome for patients with multiple sclerosis, seizures, cancer, and other chronic conditions. However, there have been few comprehensive studies that have actually measured whether cannabis is an effective treatment for pain reduction. There is an absence of multistate, multicenter clinical studies with cannabis as medicine, not only in the USA but globally. With the expansion of medical cannabis into more than 38 states in the US, this type of clinical study is now feasible. On March 11, 2020, the World Health Organization formally characterized coronavirus, COVID-19, as a global pandemic and health systems globally are continuing their efforts to manage the outbreak. Coronavirus disease COVID-19 is an infectious disease caused by a newly discovered coronavirus. With the rapidly growing pandemic of COVID-19 caused by the new and challenging to treat zoonotic SARS-CoV2 coronavirus, there is an urgent need for new therapies and prevention strategies that can help curtail disease spread and reduce mortality. Inhibition of viral entry and thereby spread constitute plausible therapeutic avenues. This study will utilize an anonymous novel online questionnaire to determine study participants' qualifying condition(s) for medical cannabis use, cannabis ingestion method, frequency of use, prescription drug use, and demographic information. Secondary factors will include evaluation of pain control, quality of life metrics, any adverse side effects from cannabis use, as well as changes in adjunctive treatments. Patients will be given medical cannabis recommendations and certifications commensurate with the state law in which the encounter occurs. The variations in mechanisms between the states for recommending, registering, certifying, and developing mandated treatment plans or doses will be adhered to; however, variations in state law and cannabis programs should not cause variation in the study design because the end-result is still the same with patients being treated with medical cannabis.
Open study recordThis is an observational study of medical marijuana manufactured and dispensed by Ilera and given as standard treatment for a variety of approved serious medical conditions as defined by individual state law. All patients who are receiving one of the four formulations (Dream, Soothe, Shine and Ease) of medical marijuana will be provided a study flyer and asked to contact the study team via phone or email. Once the study team confirms eligibility, the study team will meet the subject face-to-face most likely at their dispensary (or other mutually agreeable location) and obtain informed consent, and assent when appropriate. Initial baseline demographic information, medical history and medication inventory will be completed. Also, since it is possible that the Investigators will enroll subjects across the region, Investigators anticipate the need to seek consent over the phone for many patients. This will be done via Skype, Go to Meeting, Facetime or similar platforms so that the Investigators can have a face to face interaction with the potential subjects. Regardless of where this discussion takes place (i.e., in person or via the web), all reasonable safeguards to ensure patient privacy will be taken. Patients or their legally authorized representative (LAR) will be given sufficient (i.e., up to several hours/days) to make a decision to participate in this study. Study staff will fax or email the consent form for their signature and no study procedures will begin until the signed consent form is received by the study team. The subjects or their LARs will be instructed on obtaining the blood samples. Blood draws will be completed in the subjects' home after one of their standard doses is taken. This is a prospective PK/PD study that will include patients who are currently legally consuming one of the four medical marijuana formulations (Dream, Soothe, Shine and Ease) from Ilera Healthcare as part of their standard therapy for one of the state approved serious medical conditions. Part 1 of the study consists of intake data of select subjects. * The patients will be identified at a dispensary that offers Ilera products. * Patients be given a flyer about the study by either study staff or dispensary staff. * Eligible patients will be asked to contact the study team if they are interested in the study. * If the patient is interested, a face-to-face (in person at the dispensary or in the patients home or other agreed upon location) consent/assent will be obtained. * Also, since it is possible that Investigators will enroll subjects across the region, Investigators anticipate the need to seek consent over the phone for many patients. This will be done via Skype, Go to Meeting, Facetime or similar platforms so that the investigators can have a face to face interaction with the potential subjects. Investigators will obtain written consent in all cases. Investigators will have them sign and fax or email/scan the signed consent form back to the study team. * Once consent is obtained demographic information will be collected as well as a medical and medication history and several questions related specifically to the medical marijuana product and its perceived effectiveness. * The data will be recorded in the REDCAP database. Part 2 of the study consists of pharmacokinetic evaluation of select subjects. * Parents/ care providers/ patients when appropriate will undergo education regarding PK sample acquisition * PK blood samples will be obtained and sent to the Children's Hospital of Philadelphia (CHOP) for determination of cannibidiol/ Tetrahydrocannabinol/ cannabinol (CBD/THC/CBN) concentrations * PK and PD analysis will occur
Open study recordTo date, few studies have assessed the efficacy and safety of Cannabinoids, compounds derived from the Cannabis plant, in patients with Crohn's disease. Our study seeks to pilot a randomized, placebo-controlled trial assessing the efficacy and safety of oral cannabinoids as an adjunct therapy in patients with Crohn's disease. Crohn's disease is a type of inflammatory disease which can affect any portion of the gastrointestinal tract, from the mouth to the perianal area. Symptoms depend on location of the disease, however, many patients experience some aspect of recurrent abdominal pain, nausea, emesis, and unintentional weight loss. A common and challenging dilemma is how to manage patients who continue to have some degree of symptoms despite a common treatment regimen typically consisting of corticosteroids, thiopurines, methotrexate, or anti-TNF alpha therapies. With the recent wave of medicinal cannabis legalization in many states, many patients have begun using cannabis or commercially available cannabidiol-containing compounds as an adjunct therapy for their symptoms related to chronic inflammation and pain.
Open study recordCreate a registry that will described the natural history and landscape of medical cannabis product use in patients with chronic abdominal pain or inflammatory bowel disease. Quantitatively describe the pharmacokinetic (PK) profile of select medical cannabis products in patients with chronic neuropathic (abdominal) pain or inflammatory bowel disease. To create an educational program for families that have participated in the research for those families who opt for this component. Although these are not research in nature, they are a direct result of the proposed research and are included in the protocol to demonstrate the study's deliverables. Although the state-level legalization of cannabis for medical use allows access for patients, its use closely resembles the dietary supplement market. In 1994, the Dietary Supplement Health and Education Act (DSHEA) was passed, allowing dietary supplements to be available to consumers without prior proof of quality, safety, or efficacy. The goal of the legislation was to allow consumer access to potentially beneficial therapies without the delay from research and regulatory body approval. Unfortunately, the research did not follow, and now the dietary supplement market is an unregulated industry that is fraught with fraudulent claims and unsafe, contaminated, and/or adulterated products, many of which have unknowingly harmed individuals. Similar to dietary supplements, cannabis as a therapy is largely unstudied, with over 100 active constituents, each of which has its own potential pharmacologic actions. Different blends of these constituents have the potential to reap significant therapeutic benefits. Unfortunately, the traditional drug development paradigm has not been performed for these products. Objectives: The overall goal of this research is to characterize the current use and disposition of medical cannabis including cannabidiol (CBD) products being administered to children and adults as standard of care, and to understand the pharmacokinetics (PK) and pharmacodynamics (PD) of compounds in these medical cannabis products. An additional component of this study is to provide educational feedback to families and care providers to provide evidenced-based dosing guidance for these products to patients with qualifying gastrointestinal disorders. 1. The primary objective is to describe the natural history and landscape of medical cannabis including CBD use in patients with qualifying gastrointestinal disorders, specifically chronic abdominal pain and inflammatory bowel disease. There will be a specific focus on the variability of products and routes of administration. 2. The secondary objective is to quantitatively describe the PK profile of select medical cannabis products in patients with these gastrointestinal disorders. 3. Another secondary objective is to create an educational program for families that have participated in the research, for those families who opt for this component. Study Design: This is a prospective observational cohort study. Setting/Participants: Persons who are receiving medical cannabis as therapy, who have a diagnosis of chronic abdominal pain or inflammatory bowel disease. Study Interventions and Measures: 1. Investigators will collect demographics, data regarding utilization, formulation, indications, and concomitant medications. Investigators will do an initial intake and perform follow-up to inquire about any changes in medications or medical history on a monthly basis. 2. Once four subjects have been recruited who are taking the same formulation of a cannabis product, the study team will contact them for consent for the PK portion of the study. Investigators will collect five samples with a microsampling technique. If at any point there is a change in symptoms and/or product, Investigators will collect another five samples. The purpose of the collection is to assay for cannabis-related compounds \[(e.g. Tetrahydrocannabinol (THC), CBD)\] to quantitatively describe the PK profile. 3. Educational sessions will be created for research subjects and families who opt to participate. Investigators will hold meetings which may be in person or online and invite those interested participants to learn about our findings. This will be done at approximately six-month intervals throughout the study, or when it is deemed appropriate by the study team to share than information.
Open study recordThe purpose of the study is to investigate phospholipid ligands and their receptors in inflammatory bowel diseases and colon cancer. Several new species of lipids have been recently discovered which are able to transmit information to cancer cells in the large intestine. The lipids and their responsive receptors build an axis that is thought to influence the development of inflammation and cancer. Expression of cannabinoid receptors are examined in mucosal biopsies of the colon and blood leukocytes of patients with inflammatory bowel disease (IBD) or colon cancer in comparison to healthy individuals by polymerase chain reaction, Western Blots and flow cytometry. Colonic endoscopic biopsies and blood are collected from adult patients with confirmed active Ulcerative colitis (UC) and Crohn's disease (CD), adult UC and CD patients in remission, colon cancer patients and from healthy individuals (controls). Biopsies from healthy individuals (control group) will have undergone colonoscopy during standard screening for colorectal cancer or for the diagnostic workup of gastrointestinal symptoms without endoscopic or histologic evidence of colonic disease. For UC patients, duration and location of disease (Montreal classification), endoscopic (Mayo score) and clinical activity score, histological features and current and previous treatments (5-aminosalicylic acid, corticosteroids, immunomodulators) will be recorded. For CD patients, duration and location of disease is assessed, a HarveyBradshaw Index and activity will be scored, histological features and current and previous treatments will be recorded. Blood is collected and immediately processed for flow cytometric experiments. Phospholipids are measured in serum and in colonic mucosal biopsy samples of all cohorts by mass spectrometry.
Open study recordChronic intestinal inflammation characterizes inflammatory bowel diseases (IBD), which consist mainly of Crohn's disease and ulcerative colitis. The exact etiology is unknown for both diseases and therapeutic attempts aimed at down-regulating intestinal inflammation use both mediator-specific and nonspecific immune suppression. These attempts cause considerable side effects. Also, IBD patients are different in their genetic background and pathology. It was previously shown that products based on marijuana (Cannabis sativa) produce beneficial effects for patients with IBD, and medical cannabis-based products were formerly proven to have anti-inflammatory activity in laboratory experiments and in clinical tests. However, it is unknown how C. sativa-based medical products exert their effect in IBD and additional research and development should be done. One issue to be resolved in the process of medicalization of C. sativa is the base for the differences in patient response to different C. sativa lines, in order to fine-tune C. sativa -based treatment to IBD patients. For this aim of fine-tuning C. sativa -based treatment to IBD patients, we characterized the chemical composition of different C. sativa lines and their anti-inflammatory activities on colon cells lines. Extracts of C. sativa lines were prepared using various methods and cannabinoids and terpenoids profile was determined by chemical analysis. We found that different compounds have different effects on inflamed colon cell lines, leading to changes in interleukin secretion, inflammation markers and gene expression in the treated colon cells. In addition, we have developed a unique system relevant for personalized medicine in IBD. This system allows a patient-specific determination of the effect of C. sativa -based treatment. Following, clinical tests will be conducted aiming to develop cannabis-based products from different C. sativa lines, with anti-inflammatory activity that is effective and optimized for the different IBD patients. Title of the project: Efficacy of cannabinoids in the treatment of inflammatory bowel disease Question to be investigated: The marijuana plant, Cannabis sativa has been used as a medicinal treatment for a variety of diseases. Cannabinoids have been reported to alleviate neurological conditions including MS-related symptoms such as spasticity, pain, tremor and bladder dysfunction . Other neurological conditions, such as chronic intractable pain, dystonic movement disorders, and Tourette's Syndrome were also reported to be alleviated by cannabis use . Cannabis has been used to treat anorexia in AIDS and cancer patients. In gastroenterology, cannabis has been used to treat anorexia, emesis, abdominal pain, gastroenteritis, diarrhea, intestinal inflammation, and diabetic gastroparesis . The cannabis plant contains over 60 different compounds which are collectively referred to as cannabinoids . Of these, the two compounds delta 9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) seem to be the most active. Cannabinoids have a profound anti-inflammatory effect, mainly through the CB2 receptor. Cell mediated immunity was found to be impaired in chronic marijuana users . A potent anti-inflammatory effect of cannabis was observed in rodents. Studying the functional roles of the endocannabinoid system in immune modulation reveals that it is involved in almost all major immune events. Cannabinoids shift the balance of pro-inflammatory cytokines and anti-inflammatory cytokines towards the T-helper cell type 2 profiles (Th2 phenotype) and suppress cell-mediated immunity, whereas humoral immunity may be enhanced. Cannabidiol was shown to reduce inflammation in a mouse model of rheumatoid arthritis and type I diabetes mellitus. Therefore, cannabinoids can be used to treat various inflammatory conditions including rheumatoid arthritis and asthma. In the gut, Endocannabinoids are produced by both the serosal and mucosal component of the human intestine, and studies on cell lines have shown that human intestinal epithelial cells can produce endocannabinoids; additional sources of endocannabinoids in the gut include human endothelial cells, platelets, resident macrophages and other immune cells such as lymphocytes. CB1 and CB2 receptors are be upregulated in experimental models of inflammatory bowel disease. In a mouse model of colitis, cannabinoids were found to ameliorate inflammation, and in the human intestine, levels of Anandamide are increased during inflammation. The inflamed small intestine also has significantly elevated activity of FAAH as well as expression of CB1 cannabinoid receptors. The exact cellular targets implicated in the reduction of inflammation by cannabinoids are unknown. In a model of bronchopulmonary inflammation in mice administration of anandamide decreased TNF alpha levels in bronchoalveolar lavage fluid. Delta 9-tetrahydrocannabinol (THC) inhibits synthesis of IL-12, IL-2, IL-6, INF gamma, and T cell proliferation. Many patients with IBD report that smoking marihuana ameliorated their symptoms, but there are no clinical studies investigating that observation. We have recently published the first reported observation of use of medical cannabis in Crohn's disease. In our study, of 30 patients, 21 improved significantly after treatment with cannabis. The average Harvey Bradshaw index improved from 14 ± 6.7 to 7 ± 4.7 (P \< 0.001). Number of bowel movements was reduced from an average of eight a day to five a day and the need for other medication, particularly steroids, was significantly reduced. In view of those results we conducted a double blind placebo controlled trial in 20 active Crohn's disease patients. Patients with a Crohn's Disease Activity Index (CDAI)\>200 who did not respond to steroids, immunosuppressants or anti-TNF were randomized to receive 2 cigarettes of cannabis or placebo daily. Each cigarette contained 0.5 g of cannabis, corresponding to 11.5mg Tetrahydrocannabinol (THC). The placebo contained cannabis leaves from which THC was extracted. During treatment the CDAI changed in the cannabis group from 358 ± 99 to 139±111 (p\<0.05) and in the placebo group from 373 ± 94 to 306±143 (p=Non significant). Five patients in the cannabis group and one in the placebo group went into complete remission (CDAI \<100). Three steroid dependent patients in the cannabis group stopped steroids during the study. Patients reported improved appetite and sleep, with no serious side effects. These preliminary data indicate that cannabinoids have a great potential in the treatment of Crohn's disease, but further investigation of their influence, mode of action, active and non active cannabinoids and alternative routs of application is clearly needed. Most important is the question whether the improvement observed with cannabis consumption is only symptomatic or whether there is a real improvement in inflammation. The aim of the proposed study is to evaluate inflammation and cytokine levels in explants of colonic tissue from IBD patients with and without cannabidiol. Materials and methods: Study population: Patients with either Crohn's disease or ulcerative colitis scheduled for colonoscopy as deemed necessary by their physician will be eligible for the study. After obtaining informed consent, biopsies from inflamed and normal tissue will be taken and processed in a tissue culture media as described further. There will be 6 biopsies from each site. Methods: Explants will be cultured in groups of three with the villus surface up on microporous membranes (0.45-\_m pore size) contained in Millicell-HA tissue culture inserts (Millipore). The inserts will be placed inside 6-well plastic tissue culture dishes (Costar 3506) along with 1.5 ml of tissue culture medium. Tissue culture medium will be Dulbecco's modified Eagle's medium supplemented with 10% heat-inactivated fetal calf serum, penicillin (100units/ml), streptomycin (100 μg/ml), leupeptin (50 μg/ml), PMSF (1 mM), soybean trypsin inhibitor (50 μg/ml), and dexamethasone (200 μg/ml). Cultures will be incubated at 37°C incubator and gassed hourly with95% oxygen 5% carbon dioxide. Six biopsies from each site will be obtained. Three biopsies will serve as a control and three will be cultured with the addition of Cannabidiol (1 μg/ml). After 24 hours tissue viability will be assessed by addition of Alamar to one of each 3 samples. Change of color from purple to pink indicates viable tissue. The supernatant from the other 4 biopsies will be collected and frozen at -20°C. The biopsies will than be placed in formalin for pathology inspection. The supernatant from controlled and cannabis treated samples will be analyzed for the presence and level of TNF alpha, Interferon gamma,IL-23, IL-12, IL-2, IL-10, IL-17 and IL-6.
Open study recordThere are many anecdotal reports about improvement of Inflammatory bowel diseases (IBD) with cannabis smoking. The most effective anti inflammatory compound known today is cannabidiol. cannabidiol can be extracted from the cannabis plant, it has no central effect and is fat soluble so it can be given as drops in oil. Doses of up to 500mg did not cause any side effects. The aim of the proposed study is to examine in a double blind placebo controlled fashion the effect of cannabidiol on disease activity in patients with IBD. Background: Inflammatory bowel diseases (IBD) are relatively common disease with a rising incidence. Treatment includes various immunocompromising agents including corticosteroids, immunomodulators and biologic agents. Current treatment is not always effective and has many side effect. Cannabinoids have been known to have anti inflammatory effect, probably via the CB2 receptor. There are many anecdotal reports of cannabinoids in inflammatory disease such as rheumatoid arthritis, and the impression is that cannabinoids do have an ameliorating effect on IBD and that side effects are negligible. However, there are no placebo controled trials in human subjects. The cannabis plant contains about 600 ingredients, and it is not known which are the active ingredients affecting IBD. The most effective anti inflammatory compound known today is cannabidiol. Cannabidiol can be extracted from the cannabis plant, it has no central effect and is fat soluble so it can be given as drops in oil. Doses of up to 500mg did not cause any side effects. The aim of the proposed study is to examine in a double blind placebo controlled fashion the effect of cannabidiol on disease activity in patients with IBD.
Open study recordBackground: The marijuana plant Cannabis has been used for centuries in the medicinal treatment of many disorders and is still the subject of medical research and public debate. Cannabinoids have been purported to alleviate a variety of neurological conditions such as MS-related symptoms including spasticity, pain, tremor and bladder dysfunction. Other neurological conditions like chronic intractable pain, dystonic movement disorders and Tourette's Syndrome were all reported to be alleviated by cannabis use. Cannabis has been used to treat anorexia in AIDS and cancer patients. In gastroenterology cannabis has been used to treat symptoms and diseases including anorexia, emesis, abdominal pain, gastroenteritis, diarrhoea, intestinal inflammation and diabetic gastroparesis. Cannabinoids have also a profound anti inflammatory effect, mainly through the CB2 receptor. Cell mediated immunity may be impaired in chronic marijuana users. And a potent anti-inflammatory effect of cannabis was observed in rats . Studying the functional roles of the endocannabinoid system in immune modulation reveals that there are no major immune events which do not involve the endocannabinoid system. Cannabinoids shift the balance of pro-inflammatory cytokines and anti-inflammatory cytokines towards the T-helper cell type 2 profiles (Th2 phenotype), and suppress cell-mediated immunity whereas humoral immunity may be enhanced. They are therefore used for various inflammatory conditions including rheumatoid arthritis and asthma. In a mouse model of colitis cannabinoids were found to ameliorate inflammation and there are many anecdotal reports about the effect of cannabis in inflammatory bowel disease. However, there are no methodical reports of the effect of cannabis on inflammatory bowel disease. The aim of the proposed study is to examine in a double blind placebo controlled fashion the effect of smoking cannabis on disease activity in patients with IBD.
Open study recordHypothesis:In patients with ulcerative colitis and Crohn's disease diagnosed with mild or moderate anaemia: 1. iron supplementation will increase disease activity and oxidative stress 2. the addition of antioxidant vitamin will reduce this detrimental effect To maintain site/extent of disease and medication consistent among groups, the design is a double blind crossover placebo-controlled trial. 1. If mild anaemia, patients are randomized to 300 mg of ferrous fumarate or placebo for 4 weeks followed by 2 weeks of washout period after which patients will crossover the opposite treatments for another 4 weeks. 2. If moderate anaemia, patients will receive 600 mg of ferrous fumarate for 10 weeks. They are randomized to either vitamin E (800 IU) or placebo for 4 weeks followed by 2 weeks of washout period after which patients will crossover the opposite treatments for another 4 weeks
Open study record