Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability

NCT ID: NCT05744479

Last Updated: 2025-08-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-02-28
• Study Completion Date: 2026-12-01

Brief Summary

People with IDD (intellectual and developmental disability) have very high rates of obesity and die prematurely from cardiometabolic disease. While antipsychotics contribute to this problem, their use is necessary and appropriate in a significant subgroup of individuals with IDD. Exercise and diet interventions have limitations and may not be sufficient, requiring effective adjunctive pharmacological approaches to target obesity and related comorbidities in IDD. However, persons with IDD treated with antipsychotics are systematically excluded from clinical trials hindering development of evidence to help guide safe and effective treatment of these comorbidities. Moreover, evidence from other disorders cannot be extrapolated to IDD given inherent biological differences between disorders. This trial will address the identified gaps, which extend beyond cardiovascular morbidity and negatively impact psychosocial outcomes, in a hugely underserviced population.This is the the first RCT (randomized control trial) to examine the efficacy of metformin in overweight or obese adults with IDD who have experienced antipsychotic-induced weight gain. By generating efficacy data for a very accessible and scalable intervention, allows for guideline and implementation strategies to address a recalcitrant health problem.

Conditions

Intellectual Disability; Developmental Disability; Obesity

Study Design

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

Study Groups

Metformin (Oral)

50 participants will be administered oral metformin titrated to a maximum dose of 2000mg/day for 24 weeks.

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

Metformin oral, 2000mg/day, for 24 weeks.

Lifestyle Intervention

Intervention Type: BEHAVIORAL

Participants from both groups will meet a dietician and a diabetes educator at the study start to obtain advice regarding healthy diet, portion size, and meal planning to improve physical health. All participants will be invited to monthly group meetings to learn skills which will help them in a variety of wellness areas such as physical exercises and diet. Attendance in these sessions will be encouraged but not mandatory, and attendance will be recorded. Fidelity with these interventions will be captured using diet and physical activity questionnaires at RCT start, midpoint and end, and end of open label phase.

Placebo

50 participants will be administered an identical oral placebo for 24 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Oral placebo for 24 weeks

Lifestyle Intervention

Intervention Type: BEHAVIORAL

Participants from both groups will meet a dietician and a diabetes educator at the study start to obtain advice regarding healthy diet, portion size, and meal planning to improve physical health. All participants will be invited to monthly group meetings to learn skills which will help them in a variety of wellness areas such as physical exercises and diet. Attendance in these sessions will be encouraged but not mandatory, and attendance will be recorded. Fidelity with these interventions will be captured using diet and physical activity questionnaires at RCT start, midpoint and end, and end of open label phase.

Interventions

Metformin

Metformin oral, 2000mg/day, for 24 weeks.

Intervention Type: DRUG

Placebo

Oral placebo for 24 weeks

Intervention Type: DRUG

Lifestyle Intervention

Participants from both groups will meet a dietician and a diabetes educator at the study start to obtain advice regarding healthy diet, portion size, and meal planning to improve physical health. All participants will be invited to monthly group meetings to learn skills which will help them in a variety of wellness areas such as physical exercises and diet. Attendance in these sessions will be encouraged but not mandatory, and attendance will be recorded. Fidelity with these interventions will be captured using diet and physical activity questionnaires at RCT start, midpoint and end, and end of open label phase.

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

• Stable outpatients
• Age 16-65 years
• Diagnosed with an IDD
• On maintenance treatment with an antipsychotic (stable dose for ≥3 months).
• BMI must be ≥30 kg/m2, OR ≥27 kg/m2 with at least one weight-related comorbidity (treated or untreated) such as: hypertension, dyslipidaemia, obstructive sleep apnea, or impaired fasting glucose, OR >=25 for individuals who have gained > 5% body weight in association with AP use.
• Females of child-bearing age must be on one of the following regular contraceptives:

1. Agree to abstain from sex for the duration of the trial or

2. A barrier method of a diaphragm with spermicide and/or Latex condom or

3. An oral contraceptive agent, implantable contraceptive or an injectable contraceptive for at least six months prior to entering the study and will continue its use throughout the study, or

4. An intrauterine device, or

5. Partner has had a vasectomy at least 3 months prior to study start

Exclusion Criteria

• Females who are nursing, currently pregnant, or have a positive pregnancy test
• Clinical or laboratory evidence of uncompensated cardiovascular, endocrine, haematological, hepatic, renal, or pulmonary disease
• Previous treatment and lack of efficacy or tolerability with metformin
• History or diagnosis of Type 1 Diabetes (T1D) or Type 2 Diabetes (TD2) or fasting blood work, HbA1c > 6.5%
• History of metabolic acidosis or lactic acidosis
• Treatment with weight-lowering agents
• Medications with significant renal impact
• Major medical or surgical event in the preceding 3 months
• Acute suicidal risk.
• Moderate to severe substance use disorder, other than caffein or nicotine use disorder

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre for Addiction and Mental Health

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Centre for Addiction and Mental Health

Toronto, Ontario, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Mahavir Agarwal, MD, PhD

Role: CONTACT

mahavir.agarwal@camh.ca

4165358501 ext. 30546

Maria Papoulias

Role: CONTACT

maria.papoulias@camh.ca

4165358501 ext. 39365

Facility Contacts

Maria Papoulias, MSc

Role: primary

maria.papoulias@camh.ca

416-535-8501

Other Identifiers

024/2022

Identifier Type: -

Identifier Source: org_study_id