Intellectual DisabilityPhase 4METIDDNCT05744479
Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
A Phase 4 study testing Metformin and Lifestyle Intervention in people with Intellectual Disability and Developmental Disability, run by Centre for Addiction and Mental Health at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 to 65 years
- Conditions the study is for
- Intellectual Disability, Developmental Disability, Obesity
- What is being tested?
- Metformin and Lifestyle Intervention
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteCanada
- Study dates
- 28 Feb 2023to 1 Mar 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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:
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- 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
Who cannot join
- 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
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- 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 locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
Centre for Addiction and Mental Health
Toronto, Ontario, M6J1H3
Maria Papoulias, MSc, 416-535-8501, maria.papoulias@camh.ca
Mahavir Agarwal, PhD, MBBS, MD
About this study
Official title: Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability: A Double-Blind Randomized Control Trial
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
- Being tested
- Metformin, Placebo, Lifestyle Intervention
- Keywords
- Intellectual Disability, Developmental Disability, Obesity, Metformin
- Medical subject headings
- Intellectual Disability, Developmental Disabilities, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Metformin oral, 2000mg/day, for 24 weeks.
PlaceboDrug
Oral placebo for 24 weeks
Lifestyle InterventionBehavioural
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.
| Study group | Role | What they receive |
|---|---|---|
| Metformin (Oral) | Experimental | 50 participants will be administered oral metformin titrated to a maximum dose of 2000mg/day for 24 weeks. Receives: Drug: Metformin; Behavioral: Lifestyle Intervention |
| Placebo | Placebo comparator | 50 participants will be administered an identical oral placebo for 24 weeks. Receives: Drug: Placebo; Behavioral: Lifestyle Intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Individual's percentage change in body weight
Percentage change in body weight measured in percentage change of pounds (lbs)
Measured: 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
Percentage change in body weight measured in percentage change of pounds (lbs), expressed as a percentage
Measured: Week 0 and week 24
Between group (metformin vs placebo) absolute change in weight
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.
Measured: Week 24
Between group absolute change in waist circumference
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.
Measured: Week 24
Between group absolute change in BMI
Absolute change in BMI between metformin and placebo groups. Calculated by the mean change in BMI between the metformin and placebo groups.
Measured: Week 24
Change in whole body insulin sensitivity calculated with Matsuda Index
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.
Measured: Week 0 and Week 24
Change in beta-cell function, measured using the Insulin Secretion-Sensitivity Index-2 (ISSI-2)
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.
Measured: Week 0 and Week 24
Proportion in each group converting to impaired glucose tolerance, prediabetes, or type 2 diabetes
Measured through the change in HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) derived from the Oral Glucose Tolerance Test (OGTT).
Measured: Week 0 and Week 24
Change in cardiovascular risk factors assessed by change in C-reactive protein
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
Measured: Week 0 and Week 24
Change in cardiovascular risk factor assessed by change in fasting lipids profile
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
Measured: Week 0 and Week 24
Change in cardiovascular risk factor assessed by change in blood pressure
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.
Measured: Week 0 and Week 24
Change in visceral and liver fat content
Change in visceral and liver fat content assessed via MRI scans at week 0 and week 24.
Measured: Week 0 and Week 24
Medication Adherence
Measured through returning of blister pill packs, and assessing number of pills taken.
Measured: Week 0 to Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2023
- Study start28 Feb 2023
- Primary completion1 Mar 2027 (estimated)
- Study completion1 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Intellectual DisabilityStudies of the same condition, open and under way.
- More trials run by Centre for Addiction and Mental HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Metformin vs Placebo
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre for Addiction and Mental Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05744479
- Sponsor's protocol ID
- 024/2022
- Acronym
- METIDD
- Status last verified
- Mar 2026
- First submitted
- 13 Jan 2023
- Last updated
- 31 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability: A Double-Blind Randomized Control Trial
- ClinicalTrials.gov ID
- NCT05744479
- Acronym / sponsor ID
- METIDD / 024/2022
- Conditions
- Intellectual Disability, Developmental Disability, Obesity
- Keywords
- Intellectual Disability, Developmental Disability, Obesity, Metformin
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Centre for Addiction and Mental HealthUniversity, hospital or other
- Study start
- 28 Feb 2023 (actual)
- Primary completion
- 1 Mar 2027 (estimated)
- Study completion
- 1 Mar 2027 (estimated)
- First posted
- 27 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Metformin vs Placebo
| Arm | Type | Receives |
|---|---|---|
| Metformin (Oral) | Experimental | Drug: Metformin, Behavioral: Lifestyle Intervention50 participants will be administered oral metformin titrated to a maximum dose of 2000mg/day for 24 weeks. |
| Placebo | Placebo comparator | Drug: Placebo, Behavioral: Lifestyle Intervention50 participants will be administered an identical oral placebo for 24 weeks. |
Who may qualify
- Ages
- 16 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MetforminMetformin oral, 2000mg/day, for 24 weeks. | Drug | Metformin (Oral) |
| PlaceboOral placebo for 24 weeks | Drug | Placebo |
| Lifestyle InterventionParticipants 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. | Behavioural | Metformin (Oral), Placebo |
Primary outcome
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)
12 secondary outcomes
Proportion of participants who achieve body weight reduction ≥5%, and ≥10% in each arm
Time frame: Week 0 and week 24
Between group (metformin vs placebo) absolute change in weight
Time frame: Week 24
Between group absolute change in waist circumference
Time frame: Week 24
Between group absolute change in BMI
Time frame: Week 24
Change in whole body insulin sensitivity calculated with Matsuda Index
Time frame: Week 0 and Week 24
Change in beta-cell function, measured using the Insulin Secretion-Sensitivity Index-2 (ISSI-2)
Time frame: Week 0 and Week 24
Proportion in each group converting to impaired glucose tolerance, prediabetes, or type 2 diabetes
Time frame: Week 0 and Week 24
Change in cardiovascular risk factors assessed by change in C-reactive protein
Time frame: Week 0 and Week 24
Change in cardiovascular risk factor assessed by change in fasting lipids profile
Time frame: Week 0 and Week 24
Change in cardiovascular risk factor assessed by change in blood pressure
Time frame: Week 0 and Week 24
Change in visceral and liver fat content
Time frame: Week 0 and Week 24
Medication Adherence
Time frame: Week 0 to Week 24
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Metformin and Lifestyle Intervention in people with Intellectual Disability and Developmental Disability, run by Centre for Addiction and Mental Health at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 31 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mahavir Agarwal, MD, PhD (4165358501 ext. 30546, mahavir.agarwal@camh.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Individual's percentage change in body weight (time frame: Weeks 0, 4, 8, 12, 16, 10, 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Mar 2026.