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.
31 exact matches
Snapshot 14/09/2026Alzheimer's disease patients with BPSD
Open study recordAlzheimer's Disease
Open study recordThis is a study to evaluate the efficacy, safety, and tolerability of BMS-986368, a FAAH/MAGL inhibitor, for the treatment of agitation in participants with Alzheimer's Disease.
Open study recordCALM-IT is a Randomized, double-blind, placebo-controlled cross-over clinical trial. Safety and efficacy of cannabidiol (CBD) capsules assessed for managing agitation in patients with AD and to identify novel biomarkers of agitation severity and treatment response. This study will look at whether CBD is an effective treatment for agitation in Alzheimer's disease (AD). This naturally derived CBD is highly pure (99%) and made by a manufacturer who meets Health Canada guidelines Cannabis products are legal for purchase in Canada. Agitation is common in AD and is known to correlate with physical health problems such as falls and weight loss, AD progression, and caregiver burden. Current treatments for agitation in AD are not beneficial for everyone and there are concerns regarding their safety. Treating agitation is important in improving the quality of life of AD patients and their families and there is a need to identify safer and more effective treatments for agitation in AD. The structure of this trial is called a "cross-over study". Participants will be randomized to receive either CBD or placebo during the first of two treatment phases. They will then cross-over to the opposite treatment during the second treatment phase. Participants will be on the study treatment for a total of 19 weeks and then will be followed for 4 more weeks after finishing the study treatment. There will be 12 study visits approximately every 2 weeks and 8 telephone visits every week during the study. In addition to looking at the effectiveness of CBD in treating agitation, the researchers will also look at whether it is beneficial for other relevant outcomes for patients with AD including overall neuropsychiatric symptoms, caregiver distress, cognition, nutritional status, and pain.
Open study recordThis is a double-blind, randomized controlled trial designed to test the effects of cannabidiol (CBD) on validated biomarkers of Alzheimer's disease (AD) progression, and behavioral, neurocognitive, and clinical measures, with putative mechanisms of action. To better understand the effects of hemp-derived CBD with and without a small amount of THC, we propose a Phase II randomized clinical trial (RCT) to examine the clinical effects of Full Spectrum CBD (fsCBD, contains less than 0.3% THC) vs. Broad Spectrum CBD (bsCBD, does not contain THC), vs. a matching placebo in a population of individuals diagnosed with mild cognitive impairment (MCI). This is a double-blind, placebo-controlled, parallel group study designed to assess the efficacy of fsCBD and bsCBD, compared to a placebo control, on biomarkers of Alzheimer's disease progression, cognitive function, pain, sleep quality, anxiety, oxidative stress, and inflammation. If eligible for the study, subjects will be randomized to receive one of the conditions for 24 weeks. The current study will test the hypothesis that a moderate dose of CBD will improve measures of Alzheimer's disease progression, cognitive function, pain, sleep quality, anxiety, oxidative stress, and inflammation as compared to placebo. The study will also test whether endocannabinoids mediate the effects of CBD on these outcomes.
Open study recordThe purpose of this study is to assess the efficacy of the oral medication IGC-AD1, a THC-based (Delta-9-Tetrahydrocannabinol) formulation administered twice a day on Agitation in patients with mild to severe dementia from Alzheimer's. CALMA is a multi-center, double-blind, randomized, placebo-controlled clinical trial. The study targets participants aged 60 and older with mild to severe Alzheimer's dementia who have exhibited clinically significant agitation for at least two weeks prior to enrollment. Agitation caused by other conditions or transient symptoms must be ruled out. Eligibility is determined by a baseline Neuropsychiatric Inventory (NPI-12), Agitation subscale score of ≥4 and the International Psychogeriatric Association (IPA) criteria for agitation. The investigational medication is an oral solution containing two active ingredients: delta-9 tetrahydrocannabinol (THC) and melatonin. The treatment is administered for 42 days, followed by a two-day taper period at the end of the study. Safety oversight includes daily calls on days 2, 3, and 4, transitioning to calls every third day thereafter. These calls will review study partners logbook entries, changes in concomitant medications, and adverse events. The primary objective of the study is to evaluate the efficacy of IGC-AD1 on agitation, measured by changes in the Cohen-Mansfield Agitation Inventory (CMAI) scores from baseline to the End of treatment (EOT). The secondary objective is to assess efficacy by examining CMAI score changes from baseline to week two. Additionally, exploratory objectives are outlined in separate documentation. Blood samples will be collected during the trial for sparse pharmacokinetic (PK) analysis, blood-based CNS biomarker, and genotyping.
Open study recordA large series of recent studies have documented the frequency of the slowing of the action in brain diseases, especially vascular and neurodegenerative diseases. In stroke, the predictive value of action slowing at the acute phase for predicting post-stroke functional outcome remains poorly investigated. In neurodegenerative diseases, the diagnostic relevance of the slowing at the prodromal stage remains unknown and this diagnostic requires new tests. Finally, in terms of anatomical determinants, few studies have studied the determinants of action slowing. The objectives of this project are to Determine the diagnostic and prognostic value of action slowing assessed with new quick tests in patients with acute stroke (Neurovascular Unit) and cognitive neurodegenerative disorders (Alzheimer Disease (AD), Lewy Body disease (LBD), Fronto Temporal lobar degeneration (FTLD), Cortico Basal Degeneration (CBD) and Progressive Supra Nuclear Palsy (PSNP)) and to define the lesion determinants with VBM and VLSM
Open study recordThe Swedish BioFINDER 2 study is a new study that will launch in 2017 and extends the previous cohorts of BioFINDER 1 study (www.biofinder.se). BioFINDER 1 is used e.g. to characterize the role of beta-amyloid pathology in early diagnosis of Alzheimer's disease (AD) using amyloid-PET (18F-Flutemetamol) and Aβ analysis in cerebrospinal fluid samples. The BioFINDER 1 study has resulted in more than 40 publications during the last three years, many in high impact journals, and some the of the results have already had important implications for the diagnostic work-up patients with AD in the clinical routine practice. The original BioFINDER 1 cohort started to include participants in 2008. Since then there has been a rapid development of biochemical and neuroimaging technologies which enable novel ways to the study biological processes involved in Alzheimer's disease in living people. There has also been a growing interest in the earliest stages of AD and other neurodegenerative diseases. With the advent of new tau-PET tracers there is now an opportunity to elucidate the role of tau pathology in the pathogenesis of AD and other tauopathies. The Swedish BioFINDER 2 study has been designed to complement the BioFINDER 1 study and to e.g. address issues regarding the role of tau pathology in different dementias and in preclinical stages of different dementia diseases. Further, the clinical assessments and MRI methods have been further optimized compared to BioFINDER 1. Detailed assessments of motor aspects and dual task performance, which is part of a sub-study named Motor-ACT: "Motor aspects and activities in relation to cognitive decline and brain pathologies, has been added to further optimize assessment of motor function. GENERAL AIMS: 1. Develop methods for early and accurate diagnosis of different dementia disorders. This is important not only for the clinical diagnostic work-up, but also for selection of patients to clinical trials. Because dementia is very common among the elderly, but often misdiagnosed, we need to develop minimally invasive, reliable and affordable biomarkers for use in a primary care setting. This could include blood-based biomarkers which could be used to identify patients at high risk for a neurodegenerative disease. We also aim to develop new diagnostic algorithms using advanced imaging techniques and cerebrospinal fluid (CSF) biomarkers to diagnose patients prior to overt symptoms (when brain dysfunction is still limited and potentially reversible) in order to identify individuals more likely to respond to new disease-modifying therapies. 2. Develop biomarkers and imaging techniques to monitor early effects of new disease-modifying therapies. Methods are needed that can reliably detect relevant changes in the turnover of Aβ, tau and α-synuclein. In the present study one focus will be to study the annual change in the retention of Tau PET ligands during both the prodromal and dementia stages of AD. Further, we need biomarkers that detect the intensity of ongoing synaptic/neuronal degeneration. Imaging methods revealing the functional and structural integrity of different brain networks might also be relevant. 3. Investigate the heterogeneity of dementia and parkinsonian disorders to assist in the development of a new pathology-based disease classification. Current diagnostic work-up is based on symptomatology. However, the diseases (e.g. Alzheimer's and Parkinson's diseases) are heterogeneous with respect to clinical features and underlying pathologies. Moreover, there is also significant overlap between the diseases. Hence, today's symptom-based clinical diagnostic criteria are likely too crude to provide an etiologically meaningful classification of patients. We will therefore work towards a pathology-based disease classification, using in vivo biomarkers that reflect the underlying brain pathologies, e.g. Aβ or tau. This will be especially useful for the development of new disease-modifying therapies, which are aimed at specific brain pathologies. 4. Define the temporal evolution of pathologies in the predementia phases of Alzheimer's disease. One of the last decade's paradigm shifts in neuroscience has been the realization that AD, and likely also other neurodegenerative diseases, starts with a prolonged predementia phase. AD even starts with an asymptomatic phase, when brain pathology is present in the absence of clinical symptoms. It has become clear that we need to better understand the temporal sequence of pathologic events in these disorders to be able to select the optimal disease stages for interventions in clinical trials with different disease-modifying therapies directed at specific pathologies. 5. Investigate the underlying disease mechanisms of dementia disorders in humans aiming at finding new relevant drug targets. Drug discovery using the currently available cell and animal models, has not translated to human research as indicated by failed phase II and III trials. There are several possible reasons for these failures. First, it is possible that previous trials may have focused on the wrong drug targets, since findings from cell and animal models of dementias may not have accurately captured essential aspects of the disease mechanisms in humans. BioFINDER2 will be a translational study where we will attempt to bridge the knowledge gap between cell/animal studies and studies in humans, by using biomarkers that reflect biological mechanisms that may be studied across model systems. Second, another reason of the failed trials may be that they included patients in too advanced disease stages for the treatments to be effective, or that they partly included patients with unspecific diseases, since they did not use biomarker-based methods for inclusion of participants. BioFINDER2 will inform on the design of future clinical trials by providing detailed data about cognitive and functional changes over time in people with well-defined biomarker-characterized brain pathologies. STUDY PLAN To reach the objectives above, we include well-characterized and clinically relevant populations of patients with dementia and/or parkinsonian symptoms and healthy individuals. We apply several state of the art methodologies in order to develop new brain imaging techniques, new biomarkers in blood and CSF as well as novel methods of assessing important clinical symptoms. COGNITIVE TESTING Attention and executive function will be assessed with the Trail Making Test A and B (TMT), Symbol Digit Modalities Test (SDMT), and A Quick Test of cognitive speed (AQT). Visuospatial ability will be measured by two subtests from the Visual Objects and Space Perception (VOSP) battery, incomplete letters and cube analysis. Memory will be assessed with the Free and Cued Selective Reminding Test (FCSRT) in cohorts A and B. It will be complemented with the 10-word delayed recall test from ADAS-cog, including a recognition part. Verbal ability will be evaluated with the animal and letter S fluency tests and the 15-item short version of the Boston Naming Test. Global cognition will be assessed with the Mini-Mental State Examination (MMSE). In cohort A and B, a computerized cognitive battery focusing on memory and attention will also be performed. ASSESSMENTS OF SYMPTOMS, FUNCTIONAL ABILITIES AND GLOBAL FUNCTION Cognitive symptoms. All subjects will rate his or her memory and attention/executive function in relation to others of the same age according the Brief Anosognosia Scale (BAS). We have also added similar questions to cover the other cognitive domains. These questions have been validated against neuropsychological testing but there are data indicating that self-reported cognitive complaints are only valid in a lesser degree of cognitive impairment. To assess a broader range of cognitive complaints, the Subjective Cognitive Decline questionnaire (SCD-q) will be administered to the research subjects. Subjects from cohorts C, D and E will be assessed with cognitive impairment questionnaire (CIMP-QUEST; filled out by an informant). Functional ability. This will be evaluated with the informant-based Functional Activities Questionnaire (FAQ) or the Amsterdam IADL scale, both focus on instrumental activities of daily living (IADL) known to be affected early in cognitive decline. Global function. The global cognitive status will be evaluated using the sum of boxes score from the Clinical Dementia Rating scale (CDR) and the global deterioration scale (GDS). Behavioral and psychological symptoms in dementia (BPSD). BPSD will be assessed by clinicians using the Neuropsychiatric Inventory - Clinician rating scale (NPI-C) developed by Jeffrey Cummings. Mood and anxiety will be further assessed with the Hospital Anxiety and Depression scale (HADS). Frontal Behavioral Inventory (FBI) will be done in FTD-related conditions. Quality of Life (QoL). The overall health status will be rated by the subjects using the EQ-5D from Euro-QoL. In demented patients this will also be rated by an informant, spouse or close relative. Sleep. The presence of REM sleep behavior disorder will be evaluated with a single validated composite question derived from the Mayo Sleep Questionnaire. Sleep quality is assessed with the Sleep Scale from the Medical Outcome Study (MOS). Cognitive reserve. Premorbid cognition and cognitive reserve is approximated from the Cognitive Reserve Index questionnaire (CRI-q; subitems "Education" and "Working activity", not "Leisure time"). MOTOR ASSESSMENTS Motor aspects are evaluated as part of the sub-study Motor-ACT, which includes detailed motor assessments (including dual tasking): clinical assessments (administered by a physiotherapist), patient-reported outcomes and digital measures (see outcome measures). Detailed motor assessments are included in the following cohorts: B (older healthy controls), C (SCD/MCI with suspicion of incipient neurocognitive disorder) and E (parkinsonian disorders). CEREBROSPINAL FLUID (CSF) AND BLOOD SAMPLING AND ANALYZES Lumbar CSF samples will be collected according to a standardized protocol and will follow the principles of the Alzheimer's Association Flow Chart for CSF biomarkers. In short, lumbar puncture will be done between 9-12 am. 20-30 ml of CSF will be collected in Low Binding polypropylene tubes, which are stored on ice for 5-20 min until the CSF samples will be centrifuged (2000g, +4°C, 10 min). Thereafter, the CSF will be aliquoted in ca 1 ml portions into Low Binding polypropylene tubes followed by storage at -80°C until batch analyses. Plasma collection will be done at the same visit as the lumbar puncture. Blood will be drawn into tubes containing either EDTA (5 x 6 ml tubes) or Lithium heparin (3 x 3 ml tubes) as anticoagulant. After centrifugation (2000g, +4°C, 10 min), plasma samples will be aliquoted into polypropylene tubes and stored at -80°C pending biochemical analyses. Further, EDTA-blood (2 x 6 ml) will also be obtained for genetic DNA analyses. MAGNETIC RESONANCE IMAGING 3 Tesla MRI (Siemens Prisma) will be done in all study cohorts. A wide variety of magnetic resonance imaging (MRI) techniques will be used to study regional brain volume (three-dimensional magnetization-prepared rapid acquisition with gradient echo (3D MPRAGE)), metabolism (MR spectroscopy (MRS)), structural and functional connectivity of different brain regions (diffusion tensor imaging (DTI) and functional MRI (fMRI)), regional blood flow (arterial spin labeling (ASL)), iron deposition (susceptibility-weighted imaging (SWI)) and the presence of small vessel disease (MPRAGE, SWI and fluid-attenuated inversion recovery (FLAIR)). The protocol will take approximately 60 min to perform. No contrast-enhancing agent will be used. PET IMAGING Tau PET. PET imaging of tau aggregates will be done in all the included cohorts at baseline. In the present study, Tau PET imaging will be performed using 18F-RO6958948 developed by Hoffmann-La Roche that will provide the precursor for this PET ligand. This tau PET imaging agent has been shown to accurately detect tau pathology in cases with AD when compared to controls. We will perform a 20-30 min PET scan approximately 60 min post intravenous injection of 18F-RO6958948. The impact of the investigation on clinical diagnostic accuarcy and patient care will be investigated. 18F-RO6958948 has not yet been approved for use in clinical routine practice in Sweden, and can only be used in research studies, such as the present study. Amyloid PET. PET imaging of Aβ aggregates (including 18F-flutemetamol PET) has been approved for use in clinical routine practice in Sweden. In the present study, 18F-flutemetamol PET will be done in non-demented cases only. In the cases with dementia CSF Aβ will be enough to determine the presence or absence of brain amyloid pathology. However, in the cognitively healthy cases and in the patients with SCD or MCI we are interested in following the spread of amyloid pathology throughout the brain during the preclinical stages of AD and the spatial relationship to tau pathology. Therefore, Amyloid PET will be done according to clinical routine procedures in addition to CSF Aβ measurements in these groups. In the present study Amyloid PET will be performed using 18F-flutemetamol. GE Healthcare will provide the precursor for 18F-flutemetamol. A 20 min scan will be performed between 90-110 min post injection of 18F-flutemetamol. FDOPA PET FDOPA PET is often used as part of clinical routine examinations of patients with parkinsonism to confirm the diagnosis. Here DaTSCAN will be done according to clinical routine procedures in cases with PD, PDD, DLB, MSA, PSP and CBD to confirm the clinical diagnosis if it has not been done in clinical routine praxis within one year from the baseline visit.
Open study recordThis is an open label, eight week, clinical trial of a proprietary high CBD/low THC sublingual solution for the treatment of clinically significant anxiety and agitation in individuals with mild cognitive impairment (MCI) or mild to moderate Alzheimer's Disease (AD).
Open study recordThe participant in this study includes Alzheimer's disease (AD including familial AD and sporadic AD) patients, amnestic mild cognitive impairment (aMCI) patients, non-AD dementia patients and cognitively normal control. The purpose of this study is to establish the best cut-off value of cerebrospinal fluid (CSF) and blood β-amyloid (Aβ) 42/40, total tau (t-tau) , phosphorylated tau ,inflammatory factors, etc. in diagnosis of Alzheimer's disease (AD). 1. Incorporating patients who meet the criteria from Capital Medical University Xuanwu Hospital including AD, aMCI, non-AD dementia and cognitively normal control. 2. Collect the information of clinical and neuropsychological assessment (mini-mental state examination, MMSE, Montreal cognitive assessment, MoCA, and clinical dementia rating scale, CDR), neuroimaging data including medial temporal atrophy (MTA) score, Fazekas score, MRI, and PET(optional), as well as the biological sample, such as CSF and peripheral blood. 3. To quantify levels of Aβ42, Aβ40, t-tau, p-tau, inflammatory factors, etc. in CSF and blood. 4. Detect all participants ApoE genotype. 5. Independently establish the best cut-off value of Chinese people in our laboratory. 6. Analysis the relationships between core biomarkers in CSF/blood and ApoE genotype and neuroimaging data. 7. Establish combined diagnostic model.
Open study recordThe study will investigate the biomarkers of Aβ and Tau seeds in plasma detected by Alzheimer's disease (AD) related seeds quantitative detector (AD-seeds-detector), and their sensitivity and specificity in diagnosing AD, compared with those from age-matched cognitively normal controls, and those with other types of dementia. To perform a high throughput analysis of the amount of Aβ and Tau seeds, the investigators have developed an AD-seeds-detector, in which a fluorescence microplate reader was combined with an oscillating mixer or water-bath-type ultrasonicator. Aβ and Tau seeds have the potential to serve as biomarkers for AD. The AD-seeds-detector could detect small quantities of Aβ and Tau seeds by taking advantage of their ability to nucleate and enhance aggregation, enabling a very high amplification of the signal. This study examines the effectiveness of using the AD-seeds-detector as a novel technique for discriminating AD from cognitively normal control and non-AD dementia by detecting small Aβ and Tau seeds in plasma. This will be an observational study aiming at using the AD-seeds-detector to detect minute amounts of Aβ and Tau seeds in plasma as novel biomarkers with high sensitivity and specificity for the accurate diagnosis of AD. To achieve this goal, the investigators will conduct two studies using the AD-seeds-detector to detect the Aβ and Tau seeds in the plasma samples. Study one: A single-center cohort that consists of well-characterized AD patients (n=150), cognitively normal controls (n=100) and non-AD dementia patients (n=50). Study two: A multi-center cohort with well-characterized AD patients (n=400), cognitively normal controls (n=400) and non-AD dementia patients (n=400).
Open study recordThe aim of this study is to establish and perfect the China Cognition and Aging Study (China COAST) cohort, to clarify the epidemiology, influencing factors, genetic characteristics, pathogenesis, disease characteristics and diagnosis and treatment status of dementia and its subtypes in China. It is of great significance to establish a relatively comprehensive national database of cognitive disorders, improve the clinical diagnosis and treatment level of cognitive disorders, and formulate prevention and treatment strategies for dementia. The primary aims of China COAST are as follows: 1. To use the prospective cohort to establish a large database research platform, so as to provide comprehensive epidemiological data, clinical and neuropsychological evaluation data, biological samples, and laboratory tests and imaging data. 2. To update the prevalence and incidence rate of dementia and its subtypes every 2-3 years, and clarify the conversion pattern from normal elderly to MCI and from MCI to dementia. 3. To explore the known or unknown protective and risk factors of dementia and its major subtypes (AD, VaD, other dementia). 4. To discover new pathogenic genes and susceptible genes of dementia and its major subtypes (AD and VaD), as well as new mutation sites of known pathogenic genes. To study the genetic variation, mutation and polymorphism of PSEN1, PSEN2, APP and APOE genes in dementia patients, and to understand their distribution and roles in the pathogenesis. 5. To study the biomarkers (body fluid, genetics, imaging) with diagnostic value of MCI, AD (sporadic and familial) and VaD, to define their cut-off values, and to establish prediction models. 6. To study the diagnostic criteria of cognitive normal, MCI, dementia and their subtypes (clinical and molecular subtypes) in the cohort, and to make psychological assessment scales with high sensitivity and specificity, and in line with the characteristics of Chinese people. 7. To find potentially modifiable risk factors for dementia and to study the prevention and intervention effect of non-pharmacological treatment on APOE ε4 carriers, MCI and AD or other dementia patients，which included improvements in education, nutrition, health care, and lifestyle changes. This needs a long time follow-up. 8. To explore the relationship between dementia as well as its major subtype AD and cerebral and systemetic circulatory disorders (for example, mixed dmentia), as well as potential therapeutic strategies. 9. To carry out investigation and researches about dementia related education, improve the awareness of dementia, and strengthen the management of dementia. 10. To investigate the level of stigma and discrimination and its influencing factors in patients with Alzheimer's disease and their caregivers. This study involved participants including Mild cognitive impairment (MCI) and its subtypes、Sporadic Alzheimer's disease (SAD)、 Familial Alzheimer's disease (FAD)、Vascular dementia (VaD)、Normal control in community population and hospital population. Research contents are as follow: 1. Through the collection of basic demographic information and clinical data from the multi-center cohort, we will calculate the prevalence and incidence rate of AD, VaD, other dementia (mixed dementia, FTD, DLB, PDD, alcohol dementia, hydrocephalus dementia, post-traumatic dementia, etc.), and update the numbers every 1-2 years. 2. To clarify the conversion pattern from normal elderly to MCI and from MCI to dementia. Through the collection and analysis of current medical history, past history, family history, living habits, drug use, physical examination and other information, we will explore the protective and risk factors of dementia and its main subtypes (AD, VaD, Other dementia), including age, gender, education level, rural/urban, marital status, parental dementia history, dietary habbit, blood pressure, drinking, smoking, diabetes, hyperlipidemia, cerebrovascular disease, heart disease, depression, hearing impairment, exercise habits (Tai chi, etc.), dementia specialist influence on patients, occupation, BMI, lifestyle changes, air pollution, head injury , social contact, low-income, and other unknown protective or risk factors. To investigate the role of ApoE gene, especially ApoEε4 in the disease onset and development, and to explore the non-pharmacological interventions For the study purpose we do follow-up every 2or 3 years. 3. By using exome sequencing, GWAS, WGS and other methods, we will search for new mutations of known pathogenic genes (APP, PSEN1, PSEN2) of AD in China, find new pathogenic genes and susceptible genes of dementia and its main subtypes (AD and VaD), and understand their distribution. We will explore the independent and combined effect of susceptibility gene variation on the risk of illness in Chinese AD population, and to obtain the key mutation sites that have a clear relationship with the incidence of AD. We will do regular follow up visits for the FAD members with new mutations of pathogenic genes, and clarify the important role of new mutations of pathogenic genes during the onset and progression of AD. 4. We will collect the biofluids (blood, cerebrospinal fluid, urine, etc.) and 18F-FDG / 11C-PIB PET/MR multimodal imaging data from people with normal cognition, MCI, AD (sporadic and familial) and VaD, and conduct regular follow up. Discover and verify the SAD related susceptible gene and FAD related pathogenic gene mutation. Through analyzing the imaging data (such as MRI brain regional volume, 18F-FDG PET and cortical Aβ load), cerebrospinal fluid and plasma markers (such as Aβ, T-tau and P-tau) and clinical features (such as psychiatric symptoms and age of onset), we will develop gene chip with high sensitivity and high specificity for early screening of dementia; develop diagnostic kits for biofluid markers (blood and cerebrospinal fluid); determine imaging cut-off values at all stages of dementia in Chinese people. We will do correlation analysis to establish early diagnosis and risk prediction model for dementia, and verify the newly developed instruments that can detect the peripheral markers of dementia patients and predict the disease progression in national large sample. 5. Through the unified and standardized neuropsychological scales, including MMSE, MoCA, CDR, NPI, ADL, etc, we will conduct investigation to subjects in baseline and follow-up period, and analyze the changes of cognitive function, ability of daily life and mental behavior symptoms in different cognitive disorders. According to the social, cultural and material changes in China in recent years, we will develop psychological assessment scales with high sensitivity and specificity, and in line with the characteristics of Chinese people. Meanwhile, on the basis of the international diagnostic standards of various subtypes of dementia, combined with the etiology, clinical manifestations, scale classification, imaging characteristics, biofluid examination, etc., we will study the novel typing method and diagnostic standards of cognitive normal, MCI, dementia and its subtypes (clinical and molecular subtypes) in Chinese population. 6. Through designing randomized controlled trials, we will study the systematic and effective NPT intervention program, including lifestyle (diet and sleep habits, smoking, drinking and social networking), health products, exercise habits, cognitive training, risk factor control, etc. We will explore the quantitative and objective evaluation criteria of NPT in AD and dementia, clarify its prevention and control efficacy on APOE ε4 carriers, MCI and dementia patients, and potential neurobiological mechanism. At the same time, we will carry out dementia related education in the community, improve the public knowledge, attention and awareness of dementia, so that patients can get early detection, early diagnosis and early intervention. 7. To explore the relationship between dementia as well as its major subtype AD and cerebral circulatory disorders (cerebral ischemic and hemorrhage diseases, cerebral arteriosclerosis and stenosis, cerebral venous diseases, etc.), especially clarify the relationship between chronic cerebral ischemia and AD, as well as its effect on AD onset, and whether or not it's risk factor for AD. Whether the therapeutic strategies for cerebral circulatory disorders should be included in the treatment of AD.
Open study recordThis study tests a medication called dronabinol in people with Alzheimer's disease. First, participants go through up to 4 weeks of screening. Then, over 2 weeks, the dose of the study drug is slowly increased. For the next 10 weeks, participants stay on either dronabinol or a placebo. After finishing this part of the study, participants can join a 6-month extension where everyone receives dronabinol. Those already on the drug stay on their same dose, while those who were on placebo gradually increase their dose over 2 weeks. All participants take dronabinol for the rest of the extension, then complete a final safety check 4 weeks after stopping the medication. Usual medical treatments are continued throughout the study. This is a randomised, double-blind, placebo-controlled study conducted in patients with a diagnosis of AD. The study consists of a screening period of up to 28 days (4 weeks), a 2-week titration period, during which the dose of dronabinol is gradually increased to the target maintenance dose. This is followed by a 10-week maintenance period (Weeks 3 through 12), where the target dose is maintained. Following the 10-week maintenance period, eligible participants who complete the double-blind treatment period may enter a 6-month (24-week) open-label extension (OLE) to assess long-term safety and tolerability of dronabinol oral solution. Participants originally randomised to active treatment will continue receiving their established dose (2.5 mg, 5 mg, or 9.0 mg/day) without interruption. Participants originally randomised to placebo will undergo a 2-week titration period (Weeks 13 to 14) following the same dose escalation schedule as the main study to reach their target maintenance dose. All participants will receive open label dronabinol during the OLE period (Weeks 15 to 38). A final safety follow-up assessment will be conducted at Week 42 (4 weeks after the last dose of study medication). Standard of care medication will be maintained throughout this study for all participants as per the inclusion/exclusion criteria. Titration/Transition Schedule: Week 1/35: The starting dose will be 2.5 mg dronabinol once a day (QD) Week 2/14: Dronabinol dose will be increased to 2.5 mg twice a day (BID) for a total daily dose of 5 mg/day. Optional up-titration (Week 3/15 onwards, if tolerated) to 4.5 mg BID (total daily dose 9.0 mg/day). Note: maximum dose in this study is 4.5 mg BID. Dose escalation should occur only when a participant demonstrates BOTH: Optimal safety profile: Participant has completed ≥7 consecutive days at 5 mg/day without any clinically significant AE or group of AEs that singularly or in aggregate suggests to the Investigator or Sponsor that the study intervention is poorly tolerated and further treatment per protocol may not be safe (i.e., Grade 3 or above clinically significant AE deemed related to study intervention occurring in at least 2 study participants). Suboptimal efficacy profile: Minimal or inadequate therapeutic response, defined by specific quantitative thresholds on validated agitation scales
Open study recordThis study will look at whether nabilone is an effective treatment for agitation in Alzheimer's disease (AD) patients. Agitation is highly prevalent in patients with AD and is one of the most distressing and challenging-to-treat symptoms. Agitation is associated with faster progression to institutionalization, increased caregiver burden, poorer quality of life, and increased risk of death. In addition, current pharmacological options show only modest efficacy and elevated risks of adverse events. Therefore, identifying safer and more effective treatments for agitation in AD is a clinical and research priority. Nabilone is a synthetic cannabinoid that is Health Canada-approved to treat chemotherapy-induced nausea and vomiting. The PI's research group completed a 6-week double-blind placebo-controlled randomized cross-over pilot trial in 38 patients with moderate-to-severe AD, providing the first preliminary evidence regarding the safety and efficacy of nabilone in this population. They found that nabilone significantly improved agitation, overall neuropsychiatric symptoms, and caregiver distress. That study was limited by its sample size and questions remain regarding the efficacy of nabilone for nutrition and pain and predictors of response. However, the promising preliminary findings encourage a pivotal, practice-changing phase III trial to inform clinical practice. Participants in this study will be randomized to receive either nabilone or a placebo for 8 weeks. In addition to looking at the effectiveness of nabilone in treating agitation, the researchers will also look at whether it is beneficial for other relevant outcomes for patients with AD including overall neuropsychiatric symptoms, caregiver distress, cognition, nutritional status, and pain. Participants will also be followed for 8 weeks following completion of the study treatment.
Open study recordAlzheimer's disease and dementia with Lewy bodies (DLB) are the two main age-related neurodegenerative cognitive disorders. Differential diagnosis between these conditions is challenging, both at the prodromal and dementia stages. The lack of a precise diagnosis can be particularly harmful for patients with DLB, as up to 80% of them show severe adverse reactions to antipsychotic medications, including falls, confusion, and even death. The diagnosis of Alzheimer's disease has improved with cerebrospinal fluid (CSF) biomarkers such as Tau, phosphorylated Tau (P-Tau), and the Aβ42/Aβ40 ratio (Lehmann et al., 2018). However, differentiating Alzheimer's disease from DLB remains difficult: 1 to 3 Alzheimer's biomarkers are frequently positive in the CSF of patients with DLB: in 49% of cases at the prodromal stage and up to 72% at the dementia stage. Moreover, total α-synuclein measurement in CSF has not proven to be diagnostically reliable. The DAT-scan, sometimes used as a supportive tool, is an expensive technique and lacks sensitivity, with detection rates of only 78% in dementia-stage DLB and 54% in prodromal DLB. Given these limitations, identifying specific biomarkers for DLB, particularly pathological α-synuclein, is a critical objective. α-synuclein is the main protein component of Lewy bodies, whose abnormal β-sheet conformation promotes aggregation and prion-like propagation. Conventional measurements of total α-synuclein in CSF have failed to achieve sufficient diagnostic specificity. In contrast, detecting aggregated or pathological forms of α-synuclein in CSF appears to be a promising approach for improving the diagnosis of synucleinopathies. New techniques based on α-synuclein aggregation amplification have shown encouraging results in retrospective studies including neuropathologically confirmed cases (Bargar et al., 2021; Rossi et al., 2020). However, prospective evaluation of these methods in real-world clinical settings is still lacking. We hypothesize that a specific assay targeting pathological α-synuclein in CSF could reliably distinguish patients with DLB from those with Alzheimer's disease.
Open study recordAlzheimer's Disease (AD) has become a significant public health issue due to the increase in its incidence from 2.0 to 16.8 cases per thousand people in a year, based on 2022 data. As many countries experience population aging, there is an increase in the prevalence of AD cases, which is the main form of dementia in the elderly. It commonly begins around the age of 60, with aging being the primary risk factor. AD is a neurodegenerative disorder characterized by the presence of extracellular beta-amyloid plaques and intracellular neurofibrillary tangles of Tau protein. Among the main symptoms of AD is progressive memory loss, with varying degrees of cognitive impairment. These symptoms share common clinical features such as a progressive decline in cognitive functions, including abstract thinking, judgment, language, personality changes, and behavioral symptoms, as well as the emergence of certain comorbidities. As there are currently no curative treatments for this disease, pharmacotherapy aims to control the progressive symptoms, improving cognitive and functional aspects in patients, and consequently their quality of life. In this context, there is a need for further research to identify effective drugs that can delay or alleviate symptoms. This study is part of the second phase of the project entitled: Use of a Product Containing the Cannabinoids CBD and THC as a Treatment Strategy for Alzheimer's Disease - Alzheimer's Disease and Cannabis Clinical Trial (DAZACANN): A randomized, double-blind, placebo-controlled clinical trial previously approved by the Human Ethics Committee - CEP (CAAE 60167722.6.0000.0107). The trial is being finalized at the Laboratory of Medicinal Cannabis and Psychedelic Science, located in the city of Foz do Iguaçu, Paraná, and will continue with a new experimental design, now as an open-label trial (all participants will receive the extract and will be informed about the formulation they are receiving). The objective of this study remains to evaluate the clinical and biochemical effects of using cannabinoid-based products with low doses of purified CBD and THC, both individually and in combination, in patients with AD.
Open study recordEarly diagnosis of Neurodegenerative diseases (NDDs) and accurate patient profiling are key goals needed to tailor prompt personalized therapeutic strategies that can significantly impact disease progression and patients' quality of life. The project will validate a novel, cost-effective and quick biophotonic-based method for early and differential diagnosis of NDDs (Parkinson's disease, atypical parkinsonisms, Alzheimer's disease) and for routine clinical monitoring of NDD progression (longitudinal study). Raman spectroscopy (RS) will be applied to biochemically profile saliva and salivaderived Extracellular Vesicles (sEVs) and to identify a spectroscopic biomarker for NDDs. Optimized protocols for RS will be used to concomitantly evaluate saliva and sEVs from people with NDDs and to detect salivary changes in the biochemical profile, with special focus on EV-associated components. The accuracy of the method in discriminating NDDs at different disease stages and during disease progression will be verified. A nanotechnology-based biomolecular characterization of saliva and sEV will clarify the involvement of specific pathological molecules in NDDs progression. BACKGROUND: Neurodegenerative diseases (NDDs) are a miscellaneous group of disorders that variably affect individuals, with many subtle distinctions and different speeds across individuals and syndromes. The evolution of NDDs involves cognition, behavior and motor domains of clinical assessment that result in lifelong functional and social impairments with high economic and social costs. The biochemical pathophysiological drivers occur far earlier than symptoms appearance making the identification of subjects with preclinical disease the basis for early diagnosis, needed for an effective therapy. The clinical definition of NDDs is basically insufficient, but the molecular signals from the brain can lead to the identification of a biomarker that can be measured periodically in a non-invasive way. Therefore, a disease-specific biomarker is needed. The possibility of identifying specific markers for NDDs within saliva has recently emerged. Saliva and salivary Extracelluler Vesicles (sEVs) are vehicles for molecules associated with neuronal damage and neuroinflammation. Their isolation allows an enrichment of the molecules involved in the pathogenetic mechanisms of NDDs, improving their quantification. Raman spectroscopy (RS) is a method useful for the exhaustive biochemical characterization of saliva and its vesicular component, without staining and labeling procedures, highly informative, rapid and sustainable. In a rapid, sensitive and non-destructive way, RS provides with a spectrum that can be used as a highly specific "fingerprint" for the selected sample (e.g. saliva, blood, EV) representing the diagnostic biomarker itself. The RS study of saliva has already demonstrated the possibility of profiling patients with progressive pathologies with good accuracy and, specifically, of distinguishing subjects suffering from NDDs, with no further investigation of the ability to distinguish the NDDs at an early stage, the verification of the possibility to monitor its progression, nor the investigation of the biomolecular moieties involved in the observed differences. Raman spectroscopy is proposed as a reliable method for the rapid and exhaustive biochemical characterization of salivary and vesicular component present in the sample, without the need for staining or labeling procedures. OBJECTIVES: The objective of this project is the validation of a Raman molecular fingerprint for the considered exerimental groups, leading to the identification of a complex biomarker useful for 1) the early identification, 2) phenotyping and 3) molecular profiling of subjects with NDDs, leading to the prompt identification of tailored therapeutic strategies, including optimal pharmacological and rehabilitation therapies for each subject, with a significant impact on patients' quality of life and, in the future, on the increased probability of slowing down the progression of NDDs with optimal effective therapies. At a national level, early personalized intervention can reduce patient management times and costs. SAMPLE SIZE: Sample size was calculated with G-Power (medium effect size f=0.25, statistical power 85%, a=0.05, for ANOVA omnibus statistical test with 5 experimental groups AD, PD, AtP, pPD, MCI, drop-out rate of about 10%). The minimum number of subjects to be involved is 242. Considering the different incidence of the considered NDDs, distribution is not equal among groups. DATA COLLECTION: Demographic, clinical and research data will be pseudonymized and stored in a custom made REDCap database. NDDs diagnosis (AD, PD, AtPD, pPD or MCI), demographic (age, sex), clinical history, and comorbidities (Cumulative Illness Rating Scale) data will be stored. Saliva will be collected using an optimized protocol. SAMPLE COLLECTION: At recruitment (T0), at least 60min after the intake of food and/or drinks, saliva will be collected using Salivette tubes(Starstedt®). After 12 months(T12), subjects will be asked for a second saliva sample. Pre-analytical parameters, dietary and smoking habit will be recorded. Samples will be frozen until used. SAMPLE BIOMOLECULAR EVALUATION: SiMoA technology will be used to quantify NDDs related markers: asyn for PD, AtP and pPD, Aβ1-42 for AD and MCI, NfL as general biomarkers of neurological damage in all groups. EV ISOLATION AND CHARACTERIZATION: Saliva will be used for the isolation of EVs by Size Exclusion Chromatography (SEC) and by ultracentrifugation. Effective isolation will be verified with dot blot for protein markers, Nanoparticle Tracking Analysis (NTA) for size distribution and Transmission Electron Microscopy for morphology. RAMAN ANALYSIS: Salivary and saliva derived EV spectra will be acquired using an Aramis Raman microscope (Horiba Jobin-Yvon, France) equipped with a laser light source operating at 785 nm and 532 nm (Carlomagno et al., Frontiers, 2021; Mangolini et al., Biology, 2023). DATA PROCESSING: Acquired spectra will be baseline corrected and normalized by unit vector, to homogenize the dataset using the LabSpec6(i.e. baseline, normalization). Multivariate analysis will be used to create a classification model for AD, PD, AtPD, pPD and MCI at T0, obtaining the dispersion of the Canonical Variables. The accuracy, specificity and sensitivity of saliva and sEV RS will be calculated after the Leave-One Out Cross-Validation (LOOCV). ROC curve will be calculated. Data obtained from the molecular profiling of NDDs patients and the Raman databases will be used to interpret the spectral variation in the different experimental groups. The correlation between Raman biomolecular and clinical data will be performed to evaluate the ability of the Raman platform to stratify patients at different disease stages. The changes in the RS fingerprint between T0 and T12 will be investigated (longitudinal study) and correlated with the changes in the clinical scale scores.
Open study recordA two months intervention in which two groups of cognitive disorders, Parkinson and Alzheimer's disease, will receive 50g/day of a commercial MCT supplement combined with supervised aerobic exercise 3 times/week. Cognition and ketones will be assess before and after the intervention, along with endocannabinoids plasma concentrations.
Open study recordBrief Summary: The objective of the study is to evaluate the effect of cannabinoids on Alzheimer's Disease. This is a double-blind, randomized, placebo-controlled clinical trial. The study aims to recruit patients of both sexes diagnosed with Alzheimer's Disease who are in the mild and moderate stages for treatment with cannabinoids. The specific objectives of the study are: Primary Outcome * To evaluate the effect of Cannabis sativa at low doses according to the Mini-Mental State Examination (MMSE) scale - Memory and Cognition test - in patients with Alzheimer's Disease. Secondary Outcomes * To evaluate the effect of Cannabis sativa at low doses according to the Cornell scale - Depression in dementia test. * To evaluate the effect of Cannabis sativa at low doses according to the GDS scale - Depression in elderly people test. * To evaluate the effect of Cannabis sativa at low doses according to the QoL scale - Quality of Life test. * To evaluate the effect of Cannabis sativa at low doses according to the Epworth scale - Drowsiness test. * To evaluate the adverse effects of Cannabis sativa at low doses given daily for 26 weeks in patients with Alzheimer's Disease. Participants will use a compound containing CBD/THC 50/5 mg/mL, administered as 0.2 mL once a day. The placebo group will use a compound identical to the treatment but containing only vehicle. To address the questions above, the treated group will be compared with the placebo group over a period of 6 months. Participants will be assessed every 2 months. Additionally, blood and cerebrospinal fluid tests will be conducted to measure specific proteins related to Alzheimer's Disease and inflammatory markers. Alzheimer's disease (AD) is closely linked to the accumulation of neurotoxins derived from Aβ and tau, leading to cognitive impairment. This project posits that an imbalance in the endocannabinoid system occurs in an AD-dependent manner. Reported connections between dementia, inflammation, Aβ, and alterations in the cannabinoid system in experimental models of AD support this hypothesis. Cannabinoids may restore baseline brain function while avoiding major side effects. Despite extensive research into new AD therapies, no significant improvement has been achieved recently, and there is little consensus on how scientists will innovate to develop a new treatment. Cannabinoid-based therapy has emerged as crucial for the treatment of many diseases considered incurable. The expected results of this project will provide important insights into the ability of cannabinoids to counteract neurochemical imbalance during AD progression, thereby improving memory performance and affecting inflammation as well as Aβ and tau levels. The key point is to provide evidence that cannabinoids can serve as an efficient treatment for AD while avoiding major side effects. The aim of this project is to determine the effect of cannabinoids in AD patients, evaluating memory and cognition. It is expected that the results will establish that cannabinoids are critical for restoring the baseline function of the endocannabinoid system in AD brains and their beneficial effects. This project may be instrumental in validating new therapeutic approaches for AD. To evaluate the pharmacological activity of low doses of CBD, a double-blind, randomized, placebo-controlled clinical trial will be conducted for a duration of 6 months. A baseline assessment will be performed, and patients will be evaluated every 60 days for a period of 6 months, totaling 4 evaluation sessions. For this purpose, the following questionnaires will be applied: Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI), Geriatric Depression Scale (GDS), Alzheimer's Disease Quality of Life version patient, version caregiver and caregiver-patient version, Cornell Depression in Dementia Scale, and Epworth Sleepiness Scale. All questionnaires are references in their assessment domains and are validated for Portuguese/Brazil. In addition to the evaluation scales, biological material will be collected with blood and cerebrospinal fluid samples at baseline and at the end (after 6 months). The following analytes will be measured in the CSF: BDNF, beta-amyloid, Tau protein, TNFα, IL-6, IL-1β, and IL-10. During the research and data collection, patients' conventional treatments will not be altered. Statistical Analysis Plan SPSS software, version 29.0 will be used for the analyses. For quantitative data, the Shapiro-Wilk distribution test will be performed. Potential associations between qualitative variables will be analyzed using the Chi-Square test with adjusted residual analysis (χ²). The means (±SD) will be analyzed using the Student's t test for independent samples. Medians \[IQR\] will be calculated using the Mann-Whitney U test. Paired quantitative data will be compared individually by group across the analyzed time points using Friedman's ANOVA test. A generalized estimating equations (GEE) model, linear or with log-gamma link, and Bonferroni correction will be used to simultaneously evaluate quantitative parameters over time and between groups. For these descriptive analyses, data will be presented as means ± standard errors (±SEM). Pearson or Spearman correlations can be performed between variables of interest. For all analyses, the significance level will be set at 5%.
Open study recordAlzheimer's disease (AD) is the most prevalent neurodegenerative disease of aging. Neuropsychiatric symptoms (NPS) in AD are a major cause of burden to patients, caregivers, and society and are near-universal at some point in the AD course. One of the most troubling of these symptoms is agitation (Agit-AD), typified by a variety of problem behaviors including combativeness, yelling, pacing, lack of cooperation with care, insomnia, and restlessness. There is a great need for better interventions that target Agit-AD, a major source of patient disability as well as caregiver burden and stress, particularly in the case of moderate to severe agitation. This pilot trial could open the door to "re-purposing" Dronabinol (Marinol®) as a novel and safe treatment for Agit-AD with significant public health impact. Alzheimer's disease (AD) is the most prevalent neurodegenerative disease of aging, affecting an estimated 5.2 million Americans and predicted to increase to 13.8 million by 2050. AD affects both cognition and emotion. Neuropsychiatric symptoms (NPS) in AD are a major cause of burden to patients, caregivers, and society and are near-universal at some point in the AD course with \> 97% of AD patients having at least one symptom reported on the Neuropsychiatric Inventory (NPI). One of the most troubling of these symptoms is agitation (Agit-AD), typified by a variety of problem behaviors including combativeness, yelling, pacing, lack of cooperation with care, insomnia, and restlessness. In community-based samples, Agit-AD is common. Agit-AD is associated with greater caregiver burden and shorter time to institutionalization, and there is a particularly acute need for interventions for severe Agit-AD in advanced dementia. While there are currently no FDA approved medications for Agit-AD, psychotropic medications are widely prescribed "off-label" to treat Agit-AD. The most commonly used classes of medications prescribed for "off-label" treatment are antipsychotics and antidepressants. The evidence to date for efficacy remains mixed. Antipsychotics appear to have some degree of efficacy, but the effects are not highly replicable and it's use is associated with increased mortality in elderly patients with dementia. Antidepressants (particularly selective serotonin reuptake inhibitors, (SSRI)s) appear to have fewer and less severe adverse effects compared to antipsychotics, as well as no known mortality risks, but are not without limitation. Therefore, exploration of alternative treatments for Agit-AD, particularly severe cases, is timely and warranted. Dronabinol (Marinol®) is FDA-approved for the treatment of anorexia/weight loss in AIDS and for nausea/emesis associated with chemotherapy, which is now being used off-label for Agit-AD. Dronabinol is a synthetic oral formulation of delta-9-tetrahydrocannabinol (THC), a psychoactive constituent of the cannabis plant that acts as a partial agonist at the Type 1 (CB1) and Type 2 (CB2) endocannabinoid receptors. This pharmacology is appropriate for targeting Agit-AD because CB1 receptor agonism can produce anxiolytic and antidepressant effects and CB2 receptor agonism can be anti-inflammatory. The mechanism by which dronabinol exerts its effects on agitation and aggression in patients with dementia may occur through its action at the CB1 and/or the CB2 receptor. Agonists at the CB1 receptor in the brain improve anxiety and depression in humans as well as animal models. Dronabinol is an effective agonist at the CB1 receptor, which is generally specific to neurons and localized predominantly on the presynaptic terminal where it inhibits glutamatergic, dopaminergic and other neurotransmitter release. The CB1 receptor effects has been observed to mediate the observed anxiolytic and antidepressant effects of THC. Dronabinol is also an agonist at CB2, a potent anti-inflammatory receptor localized on activated microglia. Patients with AD have increased central and peripheral inflammation, likely as a result of the accumulation of beta-amyloid. Increased inflammation may have a number of behavioral effects that could drive the agitation and aggression in dementia patients. Dronabinol's effects at the CB2 receptor therefore could also produce changes in behavior in AD patients by reducing inflammation.
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