Schizophrenia Spectrum DisordersSemaNCT05333003
Semaglutide in Comorbid Schizophrenia Spectrum Disorder and Obesity
A study testing Semaglutide in people with Schizophrenia Spectrum Disorders, run by Centre for Addiction and Mental Health at 1 site in Canada.
Trial summary
Rates of obesity in patients with schizophrenia-spectrum disorder (SSD)s have reached epidemic proportions, with established contributing effects of antipsychotic (AP) medications. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Schizophrenia Spectrum Disorders
- What is being tested?
- Semaglutide
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 92 participants
- Where
- 1 siteCanada
- Study dates
- 25 May 2022to Aug 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Show all 18Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Semaglutide in Comorbid Schizophrenia Spectrum Disorder and Obesity for Metformin Non-responders: a Single-blind Randomized Control Trial
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).
Read the 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:
- Percentage change in body weight
- Measures of glucose metabolism and cardiovascular risk factors
- Psychopathology
- Cognition
- Lifestyle-based assessments
- Conditions
- Schizophrenia Spectrum Disorders
- Being tested
- Semaglutide, Placebo
- Keywords
- Schizophrenia spectrum disorders, GLP-1 receptor agonists, Weight, Antipsychotics
- Medical subject headings
- Body Weight
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SemaglutideDrug
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
PlaceboOther
Placebo will be provided to participants
| Study group | Role | What they receive |
|---|---|---|
| Semaglutide | Experimental | Semaglutide medication will be taken by participants on a weekly schedule, and adherence tracked Receives: Drug: Semaglutide |
| Placebo | Placebo comparator | Placebo will be taken by participants on a weekly schedule, and adherence tracked Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Weight change
Percentage change in body weight (kg)
Measured: 32 weeks
Secondary outcomes (17)
Body Mass Index (BMI)
A person's weight in kilograms divided by height in metres squared
Measured: 32 weeks
Waist circumference
Measured in centimetres
Measured: 32 weeks
Oral glucose tolerance test
A standard glucose drink (75g) is given orally, and bloodwork containing insulin (pmol/L) and glucose (mmol/L) levels are obtained both at baseline and 2 hours after the glucose drink. These measures will help indicate B cell function and whole body insulin sensitivity, allowing for the proportion of individuals converting to impaired glucose tolerance, prediabetes, or type 2 diabetes to be determined.
Measured: 32 weeks
Visceral and hepatic adiposity
An abdominal surface coil on the MRI will be used for this body composition measure
Measured: 32 weeks
Fasting lipid profile
Cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triglyceride levels will be collected through bloodwork in mmol/L
Measured: 32 weeks
Psychopathology - Brief Psychiatric Rating Scale (BPRS)
Structured scale used to measure psychiatric symptoms
Measured: 32 weeks
Psychopathology - Calgary Depression Scale for Schizophrenia (CDSS)
Structured scale used to measure depression in schizophrenia
Measured: 32 weeks
Psychopathology - Global Assessment of Functioning (GAF)
Structured scale used to rate the global functioning of patient
Measured: 32 weeks
Psychopathology - Clinical Global Impression scale (CGI)
Structured scale used to rate the global impression of patient
Measured: 32 weeks
Change in cognitive performance
Evaluated through a standard scale called the MATRICS Consensus Cognitive Battery (MCCB)
Measured: 32 weeks
Lifestyle assessment - Assessment of Quality of life (AQoL)
A structured scale used to measure health-related quality of life
Measured: 32 weeks
Lifestyle assessment - WHO Disability Assessment Schedule 2.0 (WHODAS 2.0)
A structured measure of health and disability
Measured: 32 weeks
Lifestyle assessment - International Physical Activity Questionnaire (IPAQ)
A structured measure of physical activity practices
Measured: 32 weeks
Lifestyle assessment - The Fagerstrom Test of Nicotine Dependence (FTND)
A structured scale used to measure the intensity of nicotine dependence related to cigarette smoking
Measured: 32 weeks
Lifestyle assessment - Penn State Nicotine Dependence Index-Cigarette/Electronic Cigarette
A structured measure used to quantify the intensity of physical dependence across various nicotine products
Measured: 32 weeks
Lifestyle assessment - Canadian Diet History Questionnaire II (C-DHQ II)
A structured, comprehensive questionnaire used to measure food frequency
Measured: 32 weeks
Lifestyle assessment - Food Cravings Questionnaire (FCQ)
A structured item used to measure frequency and intensity of food cravings
Measured: 32 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2022
- Study start25 May 2022
- Primary completionAug 2026 (estimated)
- Study completionAug 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Schizophrenia Spectrum DisordersStudies of the same condition, open and under way.
- More trials run by Centre for Addiction and Mental HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 92 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre for Addiction and Mental Health
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Margaret Hahn, Centre for Addiction and Mental Health
- Investigators
- Margaret Hahn, MD, PhD, Principal investigator, Centre for Addiction and Mental Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05333003
- Sponsor's protocol ID
- 139/2020
- Acronym
- Sema
- Status last verified
- May 2026
- First submitted
- 25 Mar 2022
- Last updated
- 27 May 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Semaglutide in Comorbid Schizophrenia Spectrum Disorder and Obesity for Metformin Non-responders: a Single-blind Randomized Control Trial
- ClinicalTrials.gov ID
- NCT05333003
- Acronym / sponsor ID
- Sema / 139/2020
- Conditions
- Schizophrenia Spectrum Disorders
- Keywords
- Schizophrenia spectrum disorders, GLP-1 receptor agonists, Weight, Antipsychotics
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 92 participants (estimated)
- Lead sponsor
- Centre for Addiction and Mental HealthUniversity, hospital or other
- Study start
- 25 May 2022 (actual)
- Primary completion
- Aug 2026 (estimated)
- Study completion
- Aug 2026 (estimated)
- First posted
- 18 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Percentage change in body weight
- Measures of glucose metabolism and cardiovascular risk factors
- Psychopathology
- Cognition
- Lifestyle-based assessments
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Semaglutide | Experimental | Drug: SemaglutideSemaglutide medication will be taken by participants on a weekly schedule, and adherence tracked |
| Placebo | Placebo comparator | Other: PlaceboPlacebo will be taken by participants on a weekly schedule, and adherence tracked |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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)
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SemaglutideThe 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 | Drug | Semaglutide |
| PlaceboPlacebo will be provided to participants | Other | Placebo |
Primary outcome
Weight change
Time frame: 32 weeks
Percentage change in body weight (kg)
17 secondary outcomes
Body Mass Index (BMI)
Time frame: 32 weeks
Waist circumference
Time frame: 32 weeks
Oral glucose tolerance test
Time frame: 32 weeks
Visceral and hepatic adiposity
Time frame: 32 weeks
Fasting lipid profile
Time frame: 32 weeks
Psychopathology - Brief Psychiatric Rating Scale (BPRS)
Time frame: 32 weeks
Psychopathology - Calgary Depression Scale for Schizophrenia (CDSS)
Time frame: 32 weeks
Psychopathology - Global Assessment of Functioning (GAF)
Time frame: 32 weeks
Psychopathology - Clinical Global Impression scale (CGI)
Time frame: 32 weeks
Change in cognitive performance
Time frame: 32 weeks
Lifestyle assessment - Assessment of Quality of life (AQoL)
Time frame: 32 weeks
Lifestyle assessment - WHO Disability Assessment Schedule 2.0 (WHODAS 2.0)
Time frame: 32 weeks
Lifestyle assessment - International Physical Activity Questionnaire (IPAQ)
Time frame: 32 weeks
Lifestyle assessment - The Fagerstrom Test of Nicotine Dependence (FTND)
Time frame: 32 weeks
Lifestyle assessment - Penn State Nicotine Dependence Index-Cigarette/Electronic Cigarette
Time frame: 32 weeks
Lifestyle assessment - Canadian Diet History Questionnaire II (C-DHQ II)
Time frame: 32 weeks
Lifestyle assessment - Food Cravings Questionnaire (FCQ)
Time frame: 32 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 May 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Margaret Hahn, MD, PhD principal investigator
Centre for Addiction and Mental Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Semaglutide in people with Schizophrenia Spectrum Disorders, run by Centre for Addiction and Mental Health at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 27 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Weight change (time frame: 32 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 May 2026.