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

Официальное название

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

Обзор

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.

Вмешательства

• Препарат Metformin
  Metformin oral, 2000mg/day, for 24 weeks.
• Препарат Placebo
  Oral placebo for 24 weeks
• Поведенческое Lifestyle Intervention
  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 b

Первичные конечные точки

• Individual's percentage change in body weight [Срок оценки: Weeks 0, 4, 8, 12, 16, 10, 24]

Вторичные конечные точки (12)

• Proportion of participants who achieve body weight reduction ≥5%, and ≥10% in each arm [Срок оценки: Week 0 and week 24]
• Between group (metformin vs placebo) absolute change in weight [Срок оценки: Week 24]
• Between group absolute change in waist circumference [Срок оценки: Week 24]
• Between group absolute change in BMI [Срок оценки: Week 24]
• Change in whole body insulin sensitivity calculated with Matsuda Index [Срок оценки: Week 0 and Week 24]
• Change in beta-cell function, measured using the Insulin Secretion-Sensitivity Index-2 (ISSI-2) [Срок оценки: Week 0 and Week 24]
• Proportion in each group converting to impaired glucose tolerance, prediabetes, or type 2 diabetes [Срок оценки: Week 0 and Week 24]
• Change in cardiovascular risk factors assessed by change in C-reactive protein [Срок оценки: Week 0 and Week 24]
• Change in cardiovascular risk factor assessed by change in fasting lipids profile [Срок оценки: Week 0 and Week 24]
• Change in cardiovascular risk factor assessed by change in blood pressure [Срок оценки: Week 0 and Week 24]
• Change in visceral and liver fat content [Срок оценки: Week 0 and Week 24]
• Medication Adherence [Срок оценки: Week 0 to Week 24]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Канада · 1 центр

• Centre for Addiction and Mental Health — Toronto

Идентификаторы

NCT: NCT05744479 · 024/2022

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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