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

Primary Purpose

Intellectual Disability, Developmental Disability, Obesity

Status
Not yet recruiting
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Metformin
Placebo
Lifestyle Intervention
Sponsored by
Centre for Addiction and Mental Health
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Intellectual Disability focused on measuring Intellectual Disability, Developmental Disability, Obesity, Metformin

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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: 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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    Metformin (Oral)

    Placebo

    Arm Description

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

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

    Outcomes

    Primary Outcome Measures

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

    Secondary Outcome Measures

    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
    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.
    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.
    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.
    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.
    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.
    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).
    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
    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
    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.
    Change in visceral and liver fat content
    Change in visceral and liver fat content assessed via MRI scans at week 0 and week 24.
    Medication Adherence
    Measured through returning of blister pill packs, and assessing number of pills taken.

    Full Information

    First Posted
    January 13, 2023
    Last Updated
    February 15, 2023
    Sponsor
    Centre for Addiction and Mental Health
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05744479
    Brief Title
    Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
    Acronym
    METIDD
    Official Title
    Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability: A Double-Blind Randomized Control Trial
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    February 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    February 28, 2023 (Anticipated)
    Primary Completion Date
    December 1, 2025 (Anticipated)
    Study Completion Date
    December 1, 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Centre for Addiction and Mental Health

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Intellectual Disability, Developmental Disability, Obesity
    Keywords
    Intellectual Disability, Developmental Disability, Obesity, Metformin

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 4
    Interventional Study Model
    Parallel Assignment
    Model Description
    Metformin vs Placebo
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Masking Description
    Double Blinded RCT
    Allocation
    Randomized
    Enrollment
    100 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Metformin (Oral)
    Arm Type
    Experimental
    Arm Description
    50 participants will be administered oral metformin titrated to a maximum dose of 2000mg/day for 24 weeks.
    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    50 participants will be administered an identical oral placebo for 24 weeks.
    Intervention Type
    Drug
    Intervention Name(s)
    Metformin
    Intervention Description
    Metformin oral, 2000mg/day, for 24 weeks.
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    Oral placebo for 24 weeks
    Intervention Type
    Behavioral
    Intervention Name(s)
    Lifestyle Intervention
    Intervention Description
    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 Outcome Measure Information:
    Title
    Individual's percentage change in body weight
    Description
    Percentage change in body weight measured in percentage change of pounds (lbs)
    Time Frame
    Weeks 0, 4, 8, 12, 16, 10, 24
    Secondary Outcome Measure Information:
    Title
    Proportion of participants who achieve body weight reduction ≥5%, and ≥10% in each arm
    Description
    Percentage change in body weight measured in percentage change of pounds (lbs), expressed as a percentage
    Time Frame
    Week 0 and week 24
    Title
    Between group (metformin vs placebo) absolute change in weight
    Description
    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.
    Time Frame
    Week 24
    Title
    Between group absolute change in waist circumference
    Description
    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.
    Time Frame
    Week 24
    Title
    Between group absolute change in BMI
    Description
    Absolute change in BMI between metformin and placebo groups. Calculated by the mean change in BMI between the metformin and placebo groups.
    Time Frame
    Week 24
    Title
    Change in whole body insulin sensitivity calculated with Matsuda Index
    Description
    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.
    Time Frame
    Week 0 and Week 24
    Title
    Change in beta-cell function, measured using the Insulin Secretion-Sensitivity Index-2 (ISSI-2)
    Description
    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.
    Time Frame
    Week 0 and Week 24
    Title
    Proportion in each group converting to impaired glucose tolerance, prediabetes, or type 2 diabetes
    Description
    Measured through the change in HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) derived from the Oral Glucose Tolerance Test (OGTT).
    Time Frame
    Week 0 and Week 24
    Title
    Change in cardiovascular risk factors assessed by change in C-reactive protein
    Description
    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
    Time Frame
    Week 0 and Week 24
    Title
    Change in cardiovascular risk factor assessed by change in fasting lipids profile
    Description
    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
    Time Frame
    Week 0 and Week 24
    Title
    Change in cardiovascular risk factor assessed by change in blood pressure
    Description
    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.
    Time Frame
    Week 0 and Week 24
    Title
    Change in visceral and liver fat content
    Description
    Change in visceral and liver fat content assessed via MRI scans at week 0 and week 24.
    Time Frame
    Week 0 and Week 24
    Title
    Medication Adherence
    Description
    Measured through returning of blister pill packs, and assessing number of pills taken.
    Time Frame
    Week 0 to Week 24

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    65 Years
    Accepts Healthy Volunteers
    No
    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: 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
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Mahavir Agarwal, MD, PhD
    Phone
    4165358501
    Ext
    30546
    Email
    mahavir.agarwal@camh.ca
    First Name & Middle Initial & Last Name or Official Title & Degree
    Maria Papoulias
    Phone
    4165358501
    Ext
    39365
    Email
    maria.papoulias@camh.ca

    12. IPD Sharing Statement

    Learn more about this trial

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

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