Clinical trial NCT05744479: Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
Official title: Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability: A Double-Blind Randomized Control Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Intellectual Disability
Developmental Disability
Obesity
Keywords: Intellectual Disability
Developmental Disability
Obesity
Metformin
Lead sponsor: Centre for Addiction and Mental Health
Sponsor class: OTHER
First posted: 2023-02-27
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Metformin vs Placebo
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* Stable outpatients
* Age 18-65 years
* Diagnosed with 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.
* 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

Primary outcomes:
measure: Individual's percentage change in body weight
timeFrame: Weeks 0, 4, 8, 12, 16, 10, 24
Secondary outcomes:
measure: Proportion of participants who achieve body weight reduction ≥5%, and ≥10% in each arm
timeFrame: Week 0 and week 24
measure: Between group (metformin vs placebo) absolute change in weight
timeFrame: Week 24
measure: Between group absolute change in waist circumference
timeFrame: Week 24
measure: Between group absolute change in BMI
timeFrame: Week 24
measure: Change in whole body insulin sensitivity calculated with Matsuda Index
timeFrame: Week 0 and Week 24
measure: Change in beta-cell function, measured using the Insulin Secretion-Sensitivity Index-2 (ISSI-2)
timeFrame: Week 0 and Week 24
measure: Proportion in each group converting to impaired glucose tolerance, prediabetes, or type 2 diabetes
timeFrame: Week 0 and Week 24
measure: Change in cardiovascular risk factors assessed by change in C-reactive protein
timeFrame: Week 0 and Week 24
measure: Change in cardiovascular risk factor assessed by change in fasting lipids profile
timeFrame: Week 0 and Week 24
measure: Change in cardiovascular risk factor assessed by change in blood pressure
timeFrame: Week 0 and Week 24
measure: Change in visceral and liver fat content
timeFrame: Week 0 and Week 24
measure: Medication Adherence
timeFrame: Week 0 to Week 24
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Centre for Addiction and Mental Health
state: Ontario
Study officials:
References: