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NCT Number: NCT05744479

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

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.

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Key information

Conditions

Intellectual Disability Body Weight Developmental Disabilities Developmental Disability Mental Disorders Nervous System Diseases Neurobehavioral Manifestations Neurodevelopmental Disorders Neurologic Manifestations Nutrition Disorders Nutritional and Metabolic Diseases Obesity Overnutrition Overweight Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

16 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Centre for Addiction and Mental Health

Toronto, Ontario, M6J1H3, Canada

Location status: Recruiting

Location contact

Mahavir Agarwal, PhD, MBBS, MD

PRINCIPAL_INVESTIGATOR

Maria Papoulias, MSc

CONTACT

[email protected]

416-535-8501

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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:
  • 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

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

Treatment and study plan

metformin

Drug

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

Placebo

Drug

Oral placebo for 24 weeks

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.

Primary outcomes

  1. Individual's percentage change in body weight

    Time frame: Weeks 0, 4, 8, 12, 16, 10, 24

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

Secondary outcomes

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

    Time frame: Week 0 and week 24

    Percentage change in body weight measured in percentage change of pounds (lbs), expressed as a percentage

  2. Between group (metformin vs placebo) absolute change in weight

    Time frame: Week 24

    Absolute change in body weight between metformin and placebo groups measured in pounds (lbs). Calculated by the mean change in weight between the metformin and placebo groups.

  3. Between group absolute change in waist circumference

    Time frame: Week 24

    Absolute change in waist circumstance measured in centimetres (cm) between metformin and placebo groups. Calculated by the mean change in waist circumstance between the metformin and placebo groups.

  4. Between group absolute change in BMI

    Time frame: Week 24

    Absolute change in BMI between metformin and placebo groups. Calculated by the mean change in BMI between the metformin and placebo groups.

  5. Change in whole body insulin sensitivity calculated with Matsuda Index

    Time frame: Week 0 and Week 24

    With the results of the oral glucose tolerance test at Week 0 and Week 24, insulin sensitivity was calculated with the Matsuda index.

    Insulin sensitivity was calculated with Matsuda index: [10,000 / √glucose minute 0 x insulin minute 0) (mean glucose (OGTT) x mean insulin OGTT)]. A higher result is better.

    In the formula OGTT: oral glucose tolerance test.

  6. Change in beta-cell function, measured using the Insulin Secretion-Sensitivity Index-2 (ISSI-2)

    Time frame: Week 0 and Week 24

    ISSI-2 is defined as the product of (i) insulin secretion measured by the ratio of the area-under-the-insulin-curve to the area-under-the-glucose curve and (ii) insulin sensitivity measured by the Matsuda index.

  7. Proportion in each group converting to impaired glucose tolerance, prediabetes, or type 2 diabetes

    Time frame: Week 0 and Week 24

    Measured through the change in HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) derived from the Oral Glucose Tolerance Test (OGTT).

  8. Change in cardiovascular risk factors assessed by change in C-reactive protein

    Time frame: Week 0 and Week 24

    Measured through the change in C-reactive protein (CRP) assessed at week 0 and week 24.

    Healthy levels:

    CRP: Less than 0.3 mg/dL

  9. Change in cardiovascular risk factor assessed by change in fasting lipids profile

    Time frame: Week 0 and Week 24

    Change in fasting lipid profile (low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglycerides) assessed at week 0 and week 24.

    Healthy levels:

    LDL: less than 100mg/dL HDL: 40mg/dL or higher Triglycerides: less than 150mg/dL

  10. Change in cardiovascular risk factor assessed by change in blood pressure

    Time frame: Week 0 and Week 24

    Measured through the change in blood pressure (systolic/diastolic) assessed at week 0 and week 24. A blood pressure range of 110/70 to 120/80 is considered normal.

  11. Change in visceral and liver fat content

    Time frame: Week 0 and Week 24

    Change in visceral and liver fat content assessed via MRI scans at week 0 and week 24.

  12. Medication Adherence

    Time frame: Week 0 to Week 24

    Measured through returning of blister pill packs, and assessing number of pills taken.

Study contacts

Contact information is provided by the study sponsor or research team.

Mahavir Agarwal, MD, PhD

CONTACT

[email protected]

4165358501 ext. 30546

Maria Papoulias

CONTACT

[email protected]

4165358501 ext. 39365

Sponsors and collaborators

Lead sponsor

Centre for Addiction and Mental Health

Other

Registry information

Official study title

Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability: A Double-Blind Randomized Control Trial

Acronym: METIDD

Important dates

Study start
2023
Primary completion
2027
Study completion
2027
First posted
Feb 27, 2023
Registry last updated
Mar 31, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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