Obesity
Conditions
Brief summary
Obesity is a serious health problem which increases the likelihood of developing other life-changing medical conditions. Despite increasing knowledge about the neural and metabolic basis of obesity, the development of effective anti-obesity treatment strategies has been a challenge. Evidence shows an association between cannabis consumption and body weight. However, to date, no human trials have assessed the potential of cannabis-like compounds to reduce body weight in individuals who are obese. This pilot trial aims to determine the safety and feasibility of administering nabilone (a cannabinoid drug similar to the active component of cannabis) to patients who are obese. Our secondary aims are to determine if nabilone is effective in reducing weight in this population, and to probe potential mechanisms of the weight-loss-promoting effects of nabilone, such as neural reactivity to food stimuli, changes in gut bacteria, and changes in metabolic biomarkers.
Interventions
DRUGPlacebo
Six placebo capsules taken orally twice daily
DRUGNabilone
Titrated to two 0.5 mg capsules and four placebo capsules taken orally twice daily (Low-Dose) OR Titrated to six 0.5 mg capsules taken orally twice daily (High-Dose)
Sponsors
Centre for Addiction and Mental Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
25 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* Obese adults (BMI \> 30.0 kg/m2). * For the optional imaging component of the study, a maximum weight (315 lbs) and a maximum girth in line with capacity of the machine (60 cm horizontal and 45 cm vertical; therefore, circumference of scanner is 166.6 cm) * For women of reproductive potential (WORP) and men whose sexual partners are WORP: use of adequate methods of contraception (effective barrier methods such as male condoms, female condoms, cervical caps, diaphragms, or contraceptive sponges; and highly effective methods of contraception such as oral hormonal contraceptives, intrauterine devices (IUDs), vasectomy, or tubal ligation) * AST/ALT, bilirubin, and kidney function tests within normal limits at screening.
Exclusion criteria
* Unstable gastrointestinal, respiratory, endocrinological, cardiovascular or cerebrovascular diseases that would prevent participation in the trial at QI (or its delegate) discretion, * Unstable major psychiatric disorder(s) (i.e. Axis I Disorders) that would prevent participation in the trial at QI (or its delegate) discretion, * Current substance use disorders (DSM-V) (excluding tobacco and caffeine), * History of, or current neurological illnesses, that would prevent participation in the trial, * Current use or use during the previous month of antipsychotic medications, * Learning disability, amnesia or other conditions that impede memory and attention, * Visual impairments that prevent participation in the study, * Personal or family history of schizophrenia, or psychosis (or psychosis-related) disorders, * Antibiotic use in the last 4 weeks, * Previous bariatric surgery, * Current use or use in the past month of other weight-loss pharmaceuticals, * Cannabis use in last 6 months, * Known sensitivity to cannabis or other cannabinoid agents, * Pregnancy or lactation (females), and * For the optional imaging component of the study: * Presence of metal implants or objects unsafe for MRI such as cardiac pacemakers, metal fragments in the eye, and aneurysm clips in your brain * Piercings or jewelry that are unable to be removed * Tattoos inked with metal dyes
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of SAEs Per Treatment Arm | 12 weeks of treatment | Number of SAEs collected to assess nabilone safety |
| Number of Dropouts Per Treatment Arm | 12 weeks of treatment | Number of dropouts collected to assess feasibility of study design and intervention |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Body Weight | Baseline, one weekly visit for Weeks 1-12, then one discharge visit (Week 13) | Change in body weight |
| Abdominal Fat | One scan at baseline and one scan at Week 12 | Change in abdominal fat, as measured by abdominal MRI |
| Blood Glucose Levels | Blood drawn at baseline, Week 5, Week 9, and Week 12 | Change in metabolic biomarker (blood levels of glucose) |
| Blood Insulin Levels | Blood drawn at baseline, Week 5, Week 9, and Week 12 | Change in metabolic biomarker (blood levels of insulin) |
| Blood Triglyceride Levels | Blood drawn at baseline, Week 5, Week 9, and Week 12 | Change in metabolic biomarker (blood triglyceride levels) |
| Blood Cholesterol Levels | Blood drawn at baseline, Week 5, Week 9, and Week 12 | Change in metabolic biomarker (blood levels of HDL and LDL \[total cholesterol\]) |
| Blood Leptin Levels | Blood drawn at baseline, Week 5, Week 9, and Week 12 | Change in hunger-related hormones (blood levels of leptin) |
| Blood Ghrelin Levels | Blood drawn at baseline, Week 5, Week 9, and Week 12 | Change in hunger-related hormones (blood levels of ghrelin) |
| Blood PYY Levels | Blood drawn at baseline, Week 5, Week 9, and Week 12 | Change in hunger-related hormones (blood levels of PYY) |
| Gut Microbiota | Baseline, Week 12 | Stool samples collected for quantification of gut microbiome composition; outcome measure is change in beta diversity (Bray-Curtis dissimilarity metric) from baseline to Week 12. The Bray-Curtis dissimilarity is bounded between 0 and 1, where 0 means the two sites have the same composition (i.e., pre and post samples share all the species), and 1 means the two sites do not share any species. |
| Neural Reactivity to Food vs. Control Stimuli | Baseline, Week 12 | Task-based fMRI to determine differences in neural reactivity to food vs. control pictures |
Countries
Canada
Contacts
PRINCIPAL_INVESTIGATORBernard Le Foll, MD, PhD
Centre for Addiction and Mental Health
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 32.8 years STANDARD_DEVIATION 6.7 |
| Body mass index (BMI) | 37.8 kg/m^2 STANDARD_DEVIATION 4.2 |
| Body weight | 112.2 kg STANDARD_DEVIATION 16.4 |
| Race and Ethnicity Not Collected | 0 Participants |
| Region of Enrollment Canada | 15 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 4 Participants |
| Waist circumference | 117.8 cm STANDARD_DEVIATION 18.1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 5 | 0 / 4 |
| other Total, other adverse events | 5 / 6 | 5 / 5 | 4 / 4 |
| serious Total, serious adverse events | 0 / 6 | 0 / 5 | 0 / 4 |
Outcome results
None listed