Metformin for Overweight & OBese ChILdren and Adolescents With BDS Treated With SGAs (MOBILITY)

Melissa Delbello

Status and phase: Completed; Phase 4

Conditions: Bipolar Disorder

Treatments: Drug: Metformin; Behavioral: healthy lifestyle intervention (LIFE)

Study type: Interventional

Funder types: Other

Identifiers

NCT02515773

DelBello PCORI

Details and patient eligibility

About

A prospective, large, pragmatic, randomized trial to study the impact of METFORMIN and healthy lifestyle intervention (LIFE) vs. LIFE alone on patient-centered outcomes of body weight, SGA-adherence and satisfaction, psychiatric symptom burden (e.g. mood/anxiety), and Quality of Life.

Full description

The investigators propose to recruit 1800 overweight/obese youth with Bipolar Spectrum Disorder (BSD) who are prescribed second generation anti psychotics (SGAs) from at least 24 public and private mental health practices in the Greater Cincinnati and New York City regions, (approximately 900 each from ~12 Cincinnati region and ~12 Long Island/New York mental health treatment sites) to participate in the proposed patient-centered large pragmatic trial examining the effectiveness of MET and LIFE vs. LIFE alone. Patients will be eligible if they are ages 8-17 years old, inclusive, overweight or obese (BMI > 85%), continuing or starting treatment with at least one SGA (i.e., olanzapine, clozapine, risperidone, quetiapine, aripiprazole, ziprasidone, iloperidone, lurasidone, paliperidone, or asenapine) and have a clinical diagnosis of BSD (bipolar I or II disorder, cyclothymia, or bipolar or mood disorder not otherwise specified [or by Diagnostic and Statistical Manual of Mental Disorders V (DSM-5), other specified bipolar or mood disorder). The enrollment rate will be 2-3 patients/month/site for a recruitment time of 30 months.

Enrollment: 1,565 patients

Sex: All

Ages: 8 to 19 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

1. Inpatient or outpatient age 8-19 years inclusive; participants must live with a parent, guardian, or caregiver;
2. Fluent in English;
3. Diagnosed or told by a clinician that they have any of the following bipolar spectrum disorders (BSD): bipolar I, bipolar II, unspecified bipolar and related disorders, Disruptive Mood Dysregulation Disorder (DMDD), cyclothymic disorder, other specified bipolar and related disorders, as well as mood disorder not otherwise specified (if diagnosed in the past as per DSM-IV);
4. Body mass index >85%ile for age and sex by standard growth charts;
5. Received a new or ongoing prescription for at least one SGA (i.e., olanzapine, clozapine, risperidone, quetiapine, aripiprazole, ziprasidone, iloperidone, lurasidone, paliperidone, brexpiprazole or cariprazine) that is not prescribed as a PRN medication;

Exclusion Criteria:

1. Patients will be excluded if they have had exposure to a total daily dose of MET 1000 mg bid for at least 2 weeks in the past 3 months;
2. Patients will be excluded if they could not tolerate MET during the recommended titration schedule outlined in the protocol;
3. Major neurological or medical illnesses that affect weight gain (e.g., unstable thyroid disease) or require a systemic medication that might impact weight or glucose regulation (e.g., diabetes mellitus [insulin], chronic renal failure [steroids]);
4. Fasting glucose ≥ 126 mg/dL on 2 occasions during screening indicating need for prompt treatment;
5. If lab results are available in the last 6 months, then a serum creatinine ≥1.3 mg/dL on 2 occasions during screening and/or follow-up, indicating potential impairment of renal functioning;
6. Pregnant or breast feeding;
7. Children and caregivers who are unable to complete assessments for any reason;

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,565 participants in 2 patient groups

MET and LIFE

Experimental group

Description:

Participants randomized to this group will receive both Metformin and lifestyle intervention.Participants randomized to treatment with MET will start at a dose of 500 mg orally at night and slowly titrated in 2-week intervals to ensure that each patient achieves maximum insulin-sensitizing effects of the drug while minimizing the chance of side effects. Investigators will also recommend that MET be taken with food to minimize side effects. If a participant's BMI percentile \<5% (=underweight) his/her treatment with MET will be discontinued. Although the risk of low vitamin B12 while taking MET is associated with age \> 50 years and having type II diabetes, Investigator will monitor B12 levels and a CBC throughout study participation.

Treatment:

Behavioral: healthy lifestyle intervention (LIFE)

Drug: Metformin

Healthy lifestyle intervention (LIFE)

Experimental group

Description:

Participants randomized to this group will receive just lifestyle intervention alone.This healthy lifestyle intervention (LIFE) consists of counseling participants and families regarding a healthy eating plan, physical activity and sedentary activities. Prior to study initiation, clinical site staff will participate in a live (or taped) training session from a dietician to lean to administer LIFE. A trained site staff member (e.g. medical assistant or case manager) will meet with participants and their families for a 15-20 minute session at baseline that will focus on nutritional issues using the Traffic Light Plan (TLP).

Treatment:

Behavioral: healthy lifestyle intervention (LIFE)