GWP42004
The total dose administered within any 24-hour interval will be two capsules (typically 12 hours apart).
Delta-9-tetrahydrocannabivarinLoading study record…
Loading study record…
A study to compare the change in glycaemic control in participants with Type 2 diabetes when treated with GWP42004 or placebo as add-on therapy to metformin over a period of 12 weeks. The safety and tolerability of GWP42004 compared with placebo will also be assessed.
Locally preserved from ClinicalTrials.govOpen ClinicalTrials.govlast source update 2022-12-20
What this record can show
This locally preserved record separates the registered protocol from source-reported registry results. Neither is a treatment recommendation.
Registry facts
This 14 week (one week baseline, 12 week treatment period and one week follow-up), multicentre, randomised, double blind, placebo controlled, parallel group study will evaluate the efficacy, safety and tolerability of 2, 5 and 15 mg of GWP42004 as add on to metformin compared with placebo in participants with Type 2 diabetes. Eligible participants will enter the study at a screening visit (Visit 1, Day -7) where the following information will be obtained for each participant: 1. Informed consent 2. Demographics 3. Medical history 4. Concomitant medications 5. Electrocardiogram (ECG) 6. Physical examination 7. Vital signs 8. Body weight 9. Height 10. Body Mass Index (BMI) 11. Beck Depression Inventory-II (BDI-II) 12. Safety blood test (biochemistry and haematology) 13. Efficacy blood test (HbA1c) 14. Urinalysis (including drugs of abuse screen) 15. Pregnancy test (if appropriate) Once all inclusion and exclusion criteria have been reviewed, participants will be commence a seven day baseline period. The day before Visit 2, participants will perform blood glucose tests and record the results, along with the associated time of assessment, in the study diary. Participants will then fast overnight. Participants will return to the clinic at Visit 2 (Day 1) and following review of all inclusion and exclusion criteria, the following information will be obtained for each participant: 1. Body weight 2. BMI 3. Physical examination 4. Vital signs 5. Safety blood test (biochemistry and haematology) 6. GWP42004 exposure blood test (plasma levels) 7. Efficacy blood test (HbA1c, fasting plasma glucose, serum fructosamine, fasting plasma insulin, HOMA2-IR, pro-insulin, C-peptide, HOMA2-%B, total cholesterol, HDL-cholesterol, serum triglycerides, C-reactive protein) 8. Urinalysis 9. Concomitant medications 10. Adverse events (AEs) 11. BDI-II 12. Columbia-Suicide Severity Rating Scale (C-SSRS) 13. Diabetes Treatment Satisfaction Questionnaire (DTSQs) 14. Overall health Visual Analogue Scale (VAS) 15. Cannabis withdrawal scale assessment (UK only). Participants will then be randomised to receive either GWP42004 (2, 5 or 15 mg bid) or placebo to be taken adjunctive to their currently prescribed medication. The first dose will be administered and a Oral Glucose Tolerance Test (OGTT) performed. A third (Visit 3, Day 29) and fourth (Visit 4, Day 57) visit will take place mid-treatment. The day before these visits, participants will perform blood glucose tests and record the results, along with the associated time of assessment, in the study diary. Participants will then fast overnight. The following information will be obtained for each participant at Visits 3 and 4: 1. Body weight 2. BMI 3. Physical examination 4. Vital signs 5. Safety blood test (biochemistry and haematology) 6. Efficacy blood test (HbA1c, fasting plasma glucose, fasting plasma insulin, HOMA2-IR, HOMA2-%B) 7. Urinalysis 8. Concomitant medications 9. AEs 10. BDI-II 11. C-SSRS 12. DTSQs 13. Overall health VAS A cannabis withdrawal scale assessment will be made by telephone (UK only) between Visits 4 and 5. A further visit will take place at the end of treatment (Visit 5, Day 85). Two days before this visit, a cannabis withdrawal scale assessment will be made by telephone (UK only). The day before Visit 5, participants will perform blood glucose tests and record the results, along with the associated time of assessment, in the study diary. Participants will then fast overnight. The following information will be obtained for each participant at Visit 5: the following information will be obtained for each participant: 1. Body weight 2. BMI 3. Physical examination 4. ECG 5. Vital signs 6. Safety blood test (biochemistry and haematology) 7. GWP42004 exposure blood test (plasma levels) 8. Efficacy blood test (HbA1c, fasting plasma glucose, serum fructosamine, fasting plasma insulin, HOMA2-IR, pro-insulin, C-peptide, HOMA2-%B, total cholesterol, HDL-cholesterol, serum triglycerides, C-reactive protein) 9. Urinalysis (including drugs of abuse screen) 10. Pregnancy test (if appropriate) 11. Concomitant medications 12. Adverse events (AEs) 13. BDI-II 14. OGTT 15. C-SSRS 16. DTSQs 17. Overall health VAS One, three and seven days following Visit 5 (Days 86, 89 and 92, respectively), further cannabis withdrawal scale assessments will be made by telephone (UK only). A final review of AEs and concomitant medications will be made by telephone to all participants on Day 92.
Linked local records
Local links use governed condition terms or exact source-reported intervention names. They are navigation candidates, not efficacy claims.
Interventions
The total dose administered within any 24-hour interval will be two capsules (typically 12 hours apart).
Delta-9-tetrahydrocannabivarinThe total dose administered within any 24-hour interval will be two capsules (typically 12 hours apart).
Placebo controlEligibility
primary outcomes
Time frame: Baseline (Day 1) and End of treatment (Day 85)
At baseline and at the end of treatment, a fasting blood sample is taken for measurement of HbA1c levels. Values are calculated as a percentage of total haemoglobin. A decrease from baseline to the end of treatment in base per cent values, a negative value, indicates an improvement.
secondary outcomes
Time frame: Baseline (Day 1) and End of treatment (Day 85)
At baseline and at the end of treatment, a fasting blood sample is taken for measurement of fasting plasma glucose concentrations. A decrease from baseline to the end of treatment, a negative value, indicates an improvement.
Time frame: Baseline (Day 1) and End of treatment (Day 85)
Fasting blood samples are taken at 0 minutes prior to a glucose drink and at 30 and 120 minutes post drink. The OGTT measures the serum glucose levels at two hours (120 minutes) compared to 0 minutes. The extent of the elevation in serum glucose levels following a glucose drink are compared between baseline and the end of treatment. A reduction in the elevation of serum glucose levels at the end of treatment, a negative value, indicates an improvement.
Time frame: Baseline (Day 1) and End of treatment (Day 85)
At baseline and at the end of treatment, a fasting blood sample is taken for measurement of serum fructosamine concentrations. A decrease from baseline to the end of treatment, a negative value, indicates an improvement.
Time frame: Baseline (Day 1) and End of treatment (Day 85)
At baseline and at the end of treatment, a fasting blood sample is taken for measurement of glycosylated haemoglobin A1c levels. Values are calculated as a percentage of total haemoglobin. An increase in the number of participants with HbA1c levels below 7% from baseline to the end of treatment, a positive value, indicates an improvement.
Time frame: Baseline (Day 1) and End of treatment (Day 85)
At baseline and at the end of treatment, a fasting blood sample is taken for measurement of fasting plasma insulin concentrations. An increase from baseline to the end of treatment, a positive value, indicates an improvement.
Publications
No exact PMID-linked public article is currently readable locally.
Time frame: Baseline (Day 1) and End of treatment (Day 85)
At baseline and at the end of treatment, a fasting blood sample is taken for measurement of insulin resistance calculated by HOMA2-IR. HOMA2-IR is a computer model that uses fasting plasma insulin and glucose concentrations to estimate insulin resistance, which is the reciprocal of insulin sensitivity (%S) (100/%S) as a percentage of a normal reference population (normal young adults). A decrease from baseline to the end of treatment, a negative value, indicates an improvement.
Time frame: Baseline (Day 1) and End of treatment (Day 85)
Fasting blood samples are taken at 0 minutes prior to a glucose drink and at 30 and 120 minutes post drink. The OGTT measures the serum insulin levels at two hours (120 minutes) compared to 0 minutes. The extent of the elevation in serum insulin levels following a glucose drink are compared between baseline and the end of treatment. An increase in the elevation of serum insulin levels from baseline to the end of treatment, a positive value, indicates an improvement.
Time frame: Baseline (Day 1) and End of treatment (Day 85)
At baseline and at the end of treatment, a fasting blood sample is taken for measurement of pro-insulin concentrations. A decrease from baseline to the end of treatment, a negative value, indicates an improvement.
Time frame: Baseline (Day 1) and End of treatment (Day 85)
At baseline and at the end of treatment, a fasting blood sample is taken for measurement of C-peptide concentrations. An increase from baseline to the end of treatment, a positive value, indicates an improvement.
Time frame: Baseline (Day 1) and End of treatment (Day 85)
At baseline and at the end of treatment, a fasting blood sample is taken for measurement of beta cell function calculated by HOMA2. HOMA2 is a computer model that uses fasting plasma insulin and glucose concentrations to estimate beta cell function (%B) as a percentage of a normal reference population (normal young adults). An increase from baseline to the end of treatment, a positive value, indicates an improvement.
Time frame: Baseline (Day 1) and End of treatment (Day 85)
Body Mass Index (kg/m\^2) is calculated at baseline and the end of treatment. A decrease from baseline to the end of treatment, a negative value, indicates an improvement.
Time frame: Baseline (Day 1) and End of treatment (Day 85)
At baseline and at the end of treatment, a fasting blood sample is taken for measurement of serum total cholesterol concentrations. A decrease from baseline to the end of treatment, a negative value, indicates an improvement.
Time frame: Baseline (Day 1) and End of treatment (Day 85)
At baseline and at the end of treatment, a fasting blood sample is taken for measurement of serum HDL-cholesterol. An increase from baseline to the end of treatment, a positive value, indicates an improvement.
Time frame: Baseline (Day 1) and End of treatment (Day 85)
At baseline and at the end of treatment, a fasting blood sample is taken for measurement of serum triglyceride concentrations. A decrease from baseline to the end of treatment, a negative value, indicates an improvement.
Time frame: Baseline (Day 1) and End of treatment (Day 85)
At baseline and at the end of treatment, a fasting blood sample is taken for high sensitivity measurement of CRP concentrations. A decrease from baseline to the end of treatment, a negative value, indicates an improvement.
Time frame: Baseline (Day 1) and End of treatment (Day 85)
Blood pressure is measured at baseline and at the end of treatment. A decrease from baseline to the end of treatment, a negative value, indicates an improvement.
Time frame: Baseline (Day 1) and End of treatment (Day 85)
The DTSQ (status version) is a self-administered questionnaire consisting of eight items. Six of the eight items are rated from 0 (very dissatisfied, inconvenient, inflexible, etc.) to 6 (very satisfied, convenient, flexible, etc.) and are summed to produce an Overall Treatment Satisfaction score. As such, an increase from baseline to the end of treatment, a positive value, indicates an improvement.
Time frame: Baseline (Day 1) and End of treatment (Day 85)
The DTSQ (status version) is a self-administered questionnaire consisting of eight items. Two of the eight items are used to assess 'perceived frequency of hyperglycaemia' and 'perceived frequency of hypoglycaemia', both of which are rated from 0 (none of the time) to 6 (most of the time) and are summed to produce a Glycaemic Control score. As such, a decrease from baseline to the end of treatment, a negative value, indicates an improvement.
Time frame: Baseline (Day 1) and End of treatment (Day 85)
Participants are asked to assess their overall health status using a health Visual Analogue Scale (0-100), where 100 is 'the best health you can imagine' and 0 is 'the worst health you can imagine'. An increase from baseline to the end of treatment, a positive value, indicates an improvement.
Time frame: Screening (Day -7) to Final follow-up (Day 92)
The incidence of treatment-emergent AEs is recorded for the study duration, and the number of participants who experienced an adverse event is presented.
Time frame: Baseline (Day 1) and End of treatment (Day 85)
The BDI-II is a multiple choice self-reported inventory that is one of the most widely used instruments for measuring the severity of depression. There are 21 questions or items, each having four possible responses. Each response is assigned a score ranging from zero to three, indicating the severity of the symptom. Items 1 to 13 assess symptoms that are psychological in nature, while items 14 to 21 assess symptoms that are more physical. The sum of all BDI-II item scores indicates the severity of depression. For participants eligible for this study, a score of 21 or over represents depression. The BDI-II can distinguish between different subtypes of depressive disorders, such as major depression and dysthymia. A decrease from baseline to the end of treatment, a negative value, indicates an improvement.
Time frame: Baseline (Day 1) to End of treatment (Day 85)
Participants are scored at each clinic visit for the following outcomes using the C-SSRS: suicidal ideation, suicidal behaviour, suicidality (including complete suicidality). Possible flags are as follows: "Wish to be Dead", "Non-specific Active Suicidal Thoughts", "Active Suicidal Ideation Without Intent", "Active Suicidal Ideation With Intent, No Plan", "Active Suicidal Ideation With Intent and Plan". The number of participants with a treatment-emergent flag is presented.
Time frame: Screening (Day -7) to End of treatment (Day 85)
The incidence of treatment-emergent hypoglycaemic episodes (blood glucose concentration below 3 mmol/L) is recorded for the study duration, and the number of participants who experienced a hypoglycaemic episode is presented.
Time frame: Baseline (Day 1) and Final follow-up (Day 92)
The CWS is validated and used as a diagnostic instrument in clinical and research settings where regular monitoring of withdrawal symptoms is required. The CWS will be completed for UK-based participants only. The CWS is a 19 item scale with each item (withdrawal symptom) measured on a 0-10 point scale (0 = Not at all, 5 = moderately, 10 = Extremely). For each item, the participant is asked to record the extent to which it was experienced in the last 24 hours and also to rate its negative impact on their normal daily activities (i.e., two separate scores are recorded for each item using the same 0-10 scale). Scores are summed over the 19 items for each measure, extent of experience and negative impact on normal daily activities. An increase from baseline to the end of study, a positive value, indicates withdrawal.