Semaglutide in Comorbid Schizophrenia Spectrum Disorder and Obesity

NCT ID: NCT05333003

Last Updated: 2024-03-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 92 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-25
• Study Completion Date: 2025-08-31

Brief Summary

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).

Detailed Description

People with SSDs die early of iatrogenic cardiometabolic disease. Clinically, metformin remains the first line agent to mitigate this risk. In real-world clinical practice, metformin is likely to remain the first line treatment for AP-induced weight gain (given low cost, efficacy, and safety data). However, metformin is only effective in ~20% of patients. Hence, there is a need for interventions for AP-induced weight gain non-responsive to metformin. GLP-1RAs might represent the next rational step as they have a good safety profile, advantages of weekly administration, and early efficacy evidence to support their use in SSD and comorbid obesity, with benefits on dysglycemia, and visceral adiposity. Semaglutide, recently approved for chronic weight loss is an attractive option given a similar adverse effect profile but superior metabolic efficacy compared to other GLP-1 agents. The observations supporting an association between metabolic perturbations and cognition, along with preliminary evidence for neuroprotective effects of GLP-1RAs, suggest that by modifying metabolic risk factors, the investigators may be able to target difficult-to-treat domains of the illness such as cognitive dysfunction.

This study will examine the effect of semaglutide on:

1. Percentage change in body weight

2. Measures of glucose metabolism and cardiovascular risk factors

3. Psychopathology

4. Cognition

5. Lifestyle-based assessments

Conditions

Schizophrenia Spectrum Disorders

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Semaglutide

Semaglutide medication will be taken by participants on a weekly schedule, and adherence tracked

Group Type: EXPERIMENTAL

Semaglutide

Intervention Type: DRUG

The semaglutide dose will start with 0.25 mg/week, and slowly increased every four weeks as tolerated up to a maximal dose of 2 mg/week

Placebo

Placebo will be taken by participants on a weekly schedule, and adherence tracked

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo will be provided to participants

Interventions

Semaglutide

The semaglutide dose will start with 0.25 mg/week, and slowly increased every four weeks as tolerated up to a maximal dose of 2 mg/week

Intervention Type: DRUG

Placebo

Placebo will be provided to participants

Intervention Type: OTHER

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre for Addiction and Mental Health

OTHER

Sponsor Role: lead

Responsible Party

Margaret Hahn

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Margaret Hahn, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Centre for Addiction and Mental Health

Locations

Centre for Addiction and Mental Health

Toronto, Ontario, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Margaret Hahn, MD, PhD

Role: CONTACT

margaret.hahn@camh.ca

416-535-8501 ext. 34368

Mahavir Agarwal, MD, PhD

Role: CONTACT

mahavir.agarwal@camh.ca

416-535-8501 ext. 30546

Facility Contacts

Margaret Hahn, MD, PhD

Role: primary

margaret.hahn@camh.ca

416-535-8501 ext. 34368

Other Identifiers

139/2020

Identifier Type: -

Identifier Source: org_study_id