A Pilot Trial of Nabilone for the Treatment of Obesity

Study Overview
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Brief Summary
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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.

Official Title
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Impact of Chronic Nabilone Self-administration on Body Weight, Metabolic Markers, Gut Microbiota, and Neural Circuitry in Human Obesity

Conditions
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Obesity

Intervention / Treatment
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* Drug: Placebo
* Drug: Nabilone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Six placebo capsules taken orally twice daily<br>|
| Experimental: Low-Dose Nabilone<br>pms-nabilone titrated to 2 mg daily | Drug: Nabilone<br>* 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)<br>|
| Experimental: High-Dose Nabilone<br>pms-nabilone titrated to 6 mg daily | Drug: Nabilone<br>* 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)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of SAEs per treatment arm | Number of SAEs collected to assess nabilone safety | 12 weeks of treatment | 
| Number of dropouts per treatment arm | Number of dropouts collected to assess feasibility of study design and intervention | 12 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body weight | Change in body weight | Baseline, then weekly for 12 weeks of treatment | 
| Abdominal fat | Change in abdominal fat, as measured by abdominal MRI | One scan at baseline and one scan at Week 12 | 
| Blood glucose levels | Change in metabolic biomarker (blood levels of glucose) | Blood drawn at baseline, Week 5, Week 9, and Week 12 | 
| Blood insulin levels | Change in metabolic biomarker (blood levels of insulin) | Blood drawn at baseline, Week 5, Week 9, and Week 12 | 
| Blood triglyceride levels | Change in metabolic biomarker (blood triglyceride levels) | Blood drawn at baseline, Week 5, Week 9, and Week 12 | 
| Blood cholesterol levels | Change in metabolic biomarker (blood levels of HDL and LDL) | Blood drawn at baseline, Week 5, Week 9, and Week 12 | 
| Blood leptin levels | Change in hunger-related hormones (blood levels of leptin) | Blood drawn at baseline, Week 5, Week 9, and Week 12 | 
| Blood ghrelin levels | Change in hunger-related hormones (blood levels of ghrelin) | Blood drawn at baseline, Week 5, Week 9, and Week 12 | 
| Blood PYY levels | Change in hunger-related hormones (blood levels of PYY) | Blood drawn at baseline, Week 5, Week 9, and Week 12 | 
| Gut microbiota | Stool samples collected for quantification of gut microbiome composition | Baseline, Week 12 | 
| Neural reactivity to food vs. control stimuli | Task-based fMRI to determine differences in neural reactivity to food vs. control pictures | Baseline, Week 12 |