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

Center for Addiction and Mental Health (CAMH)

Status and phase: Enrolling; Phase 4

Conditions: Obesity; Developmental Disability; Intellectual Disability

Treatments: Drug: Metformin; Drug: Placebo; Behavioral: Lifestyle Intervention

Study type: Interventional

Funder types: Other

Identifiers

NCT05744479

024/2022

Details and patient eligibility

About

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.

Enrollment: 100 estimated patients

Sex: All

Ages: 16 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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100 participants in 2 patient groups, including a placebo group

Metformin (Oral)

Experimental group

Description:

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

Treatment:

Behavioral: Lifestyle Intervention

Drug: Metformin

Placebo

Placebo Comparator group

Description:

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

Treatment:

Behavioral: Lifestyle Intervention

Drug: Placebo