Semaglutide in Comorbid Schizophrenia Spectrum Disorder and Obesity for Metformin Non-responders: a Single-blind Randomized Control Trial

139/2020

Rates of obesity in patients with schizophrenia-spectrum disorder (SSD)s have reached epidemic proportions, with established contributing effects of antipsychotic (AP) medications. Among agents approved for chronic weight management, glucagon-like peptide-1 receptor agonists (GLP-1RA) are associated with reductions in cardiovascular mortality, with recent FDA approval for once weekly semaglutide for this indication. This study will investigate whether semaglutide is effective in reducing body weight in overweight or obese individuals with SSDs who are on APs and do not demonstrate adequate weight loss on metformin (the first line treatment for weight loss in SSDs).

2022-05-25

2025-08-01

2025-08-01

Recruiting

92

Inclusion Criteria: * Stable outpatients or inpatients aged 18-70 years, diagnosed with schizophrenia spectrum disorder, or major depressive disorder with psychotic features, or bipolar disorder (does not need to have psychotic features) * On maintenance treatment with an AP (stable dose for ≥3 months) * BMI must be ≥30 kg/m2, OR ≥27 kg/m2 with the presence of at least one weight-related comorbidity (treated or untreated): hypertension, dyslipidaemia, obstructive sleep apnea, or impaired fasting glucose, OR BMI ≥25 with individual having gained \>5% bodyweight in association with AP treatment * History of either failure to tolerate metformin or failure to lose ≥5% body weight over at least 16 weeks on the highest tolerated trial of metformin, and who are not currently being treated with metformin (minimum of 1 week metformin-free prior to study entry) Exclusion Criteria: * Patients with severe substance disorder other than tobacco or caffeine use disorder; only severe substance use disorder is exclusionary for cannabis use * Liver, or renal dysfunction * A positive drug urine screen other than cannabis as per PI discretion * Sexually active females of child-bearing age not on a regular contraceptive, or nursing or with a positive pregnancy test * Clinical or laboratory evidence of uncompensated cardiovascular, endocrine, haematological, or pulmonary disease * History of reactive hypoglycaemia * Treatment within 3 months, or failure to tolerate GLP-1RA * Type 1 Diabetes (T1D) or current diagnosis of Type 2 Diabetes (T2D), diagnosis of T2D on OGTT screen, or HbA1c \> 6.5% * Use of Health Canada approved weight-lowering agents, warfarin, coumarin derivatives, or medication with significant renal impact * Major medical or surgical event within the preceding 3 months * Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome * History of pancreatitis or elevated amylase on screen * History of severe gastrointestinal disease, (i.e. gastroparesis) * Acute suicidal risk * Uncompensated thyroid disorder * History of heart rhythm disturbances, conduction system abnormalities, or evidence of clinically relevant abnormalities on screening ECG. * Any condition that interferes with the safe acquisition of MRI data such as metal implants, pacemakers, aneurysm clips, cochlear implants (only for the MRI component; can participate in the remainder of the trial) * History of gallstones with intact gallbladder or those at increased risk of gallbladder complications (with intact gallbladder)

{'studyType': 'INTERVENTIONAL', 'phases': ['NA'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'SINGLE', 'whoMasked': ['PARTICIPANT']}}, 'enrollmentInfo': {'count': 92, 'type': 'ESTIMATED'}}

2024-03-05