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

NCT05744479 | Recruiting Phase 4

• 1 other identifier: 024/2022
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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

Developmental Disability; Obesity; Intellectual Disability

Keywords

Intellectual Disability; Developmental Disability; Obesity; Metformin

Outcome Measures

Primary Outcomes (1)

• Individual's percentage change in body weight

  Percentage change in body weight measured in percentage change of pounds (lbs)

  Weeks 0, 4, 8, 12, 16, 10, 24

Secondary Outcomes (12)

• Proportion of participants who achieve body weight reduction ≥5%, and ≥10% in each arm

  Week 0 and week 24

• Between group (metformin vs placebo) absolute change in weight

  Week 24

• Between group absolute change in waist circumference

  Week 24

• Between group absolute change in BMI

  Week 24

• Change in whole body insulin sensitivity calculated with Matsuda Index

  Week 0 and Week 24

Study Arms (2)

Metformin (Oral)

EXPERIMENTAL

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

Drug: Metformin; Behavioral: Lifestyle Intervention

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo; Behavioral: Lifestyle Intervention

Interventions

Metformin DRUG

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

Metformin (Oral)

Placebo DRUG

Oral placebo for 24 weeks

Placebo

Lifestyle Intervention 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.

Metformin (Oral); Placebo

Eligibility Criteria

• Age: 16 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Agree to abstain from sex for the duration of the trial or
• A barrier method of a diaphragm with spermicide and/or Latex condom or
• 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
• An intrauterine device, or
• Partner has had a vasectomy at least 3 months prior to study start

You may not qualify if:

• 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

Sponsors & Collaborators

• Centre for Addiction and Mental Health: lead

Study Sites (1)

Centre for Addiction and Mental Health

Toronto, Ontario, M6J1H3, Canada

RECRUITING

MeSH Terms

Conditions

Intellectual Disability; Developmental Disabilities; Obesity

Interventions

Metformin

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurodevelopmental Disorders; Mental Disorders; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Central Study Contacts

Mahavir Agarwal, MD, PhD

CONTACT

4165358501; mahavir.agarwal@camh.ca

Maria Papoulias

CONTACT

4165358501; maria.papoulias@camh.ca

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double Blinded RCT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Metformin vs Placebo

Study Record Dates

• First Submitted: January 13, 2023
• First Posted: February 27, 2023
• Study Start: February 28, 2023
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: March 31, 2026

Record last verified: 2026-03

Locations

CA (1)