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

MOBILITY- Metformin for Overweight & OBese ChILdren and Adolescents With BIpolar Spectrum Disorders Treated With Second-Generation AntipsYchotics

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.

Study Overview

• Status: Completed
• Conditions: Bipolar Disorder
• Intervention / Treatment: Drug: Metformin; Behavioral: healthy lifestyle intervention (LIFE)

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 1565
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Covington, Kentucky, United States, 41011
      • The Children's Home of Northern Kentucky
  • New Jersey
    • Neptune, New Jersey, United States, 07753
      • Jersey Shore Medical Center
  • New York
    • Amityville, New York, United States, 11701
      • South Oaks
    • Brooklyn, New York, United States, 11203
      • SUNY Downstate/ Kings County Hospital
    • Brooklyn, New York, United States, 11219
      • Maimonides
    • Brooklyn, New York, United States, 11233
      • NYCCC
    • Glen Oaks, New York, United States, 11004
      • Northwell Zucker Long Island Jewish Hospital
    • New York, New York, United States, 10029
      • Mount Sinai
    • New York, New York, United States, 11004
      • LIJ Zucker Hillside Hospital
    • Queens, New York, United States, 11373
      • Child Center of New York,
    • Roslyn Heights, New York, United States, 11577
      • NorthShore Child and Family Guidance
    • Stony Brook, New York, United States, 11794
      • StonyBrook
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
    • Cincinnati, Ohio, United States, 45206
      • Lighthouse Youth Services
    • Cincinnati, Ohio, United States, 45219
      • Central Clinic
    • Cincinnati, Ohio, United States, 45227
      • Children's Home
    • Cincinnati, Ohio, United States, 45229
      • Resident Mood Medication Clinic
    • Cincinnati, Ohio, United States, 45237
      • St. Aloysius
    • Cincinnati, Ohio, United States, 45238
      • Talbert House
    • Cincinnati, Ohio, United States, 45239
      • St. Joseph's Orphanage
    • Cincinnati, Ohio, United States, 45244
      • Child Focus
    • Cincinnati, Ohio, United States, 45246
      • NECCO
    • Cleveland, Ohio, United States, 44106
      • University Hospital Medical Center Cleveland
    • Columbus, Ohio, United States, 43210
      • Ohio State University
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital Columbus
    • Dayton, Ohio, United States
      • South Community
    • Hamilton, Ohio, United States, 45011
      • Butler Behavioral Health Services
    • Xenia, Ohio, United States, 45385
      • TCN Family Solutions
  • Texas
    • Austin, Texas, United States, 78712
      • Seton Family of Hospitals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 13 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MET and LIFE; 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.	Drug: Metformin; Metformin - to achieves maximum insulin-sensitizing effects; Other Names: GLUCOPHAGE; Behavioral: healthy lifestyle intervention (LIFE); Healthy Life style intervention; Other Names: LIFE
Experimental: Healthy lifestyle intervention (LIFE); 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).	Behavioral: healthy lifestyle intervention (LIFE); Healthy Life style intervention; Other Names: LIFE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in BMI Z-score From Baseline to Month 6 in ITT Sample	Raw body mass index (BMI) is calculated as (weight(kg)/ height(m)2). This raw BMI value is converted to a normalized BMI z-score, adjusted for age and sex using US Centers for Disease Control and Prevention growth charts. A z-score equal to 0 indicates the population mean and larger z-scores are heavier weights and worse outcomes.	Baseline to Month 6
Change in BMI Z-score From Baseline to Month 24 in ITT Sample	Raw body mass index (BMI) is calculated as (weight(kg)/ height(m)2). This raw BMI value is converted to a normalized BMI z-score, adjusted for age and sex using US Centers for Disease Control and Prevention growth charts. A z-score equal to 0 indicates the population mean and larger z-scores are heavier weights and worse outcomes.	Baseline to Month 24
Change in BMI Z-score From Baseline to Month 6 in Per Protocol Sample	Raw body mass index (BMI) is calculated as (weight(kg)/ height(m)2). This raw BMI value is converted to a normalized BMI z-score, adjusted for age and sex using US Centers for Disease Control and Prevention growth charts. A z-score equal to 0 indicates the population mean and larger z-scores are heavier weights and worse outcomes.	Baseline to Month 6
Change in BMI Z-score From Baseline to Month 24 in Per Protocol Sample	Raw body mass index (BMI) is calculated as (weight(kg)/ height(m)2). This raw BMI value is converted to a normalized BMI z-score, adjusted for age and sex using US Centers for Disease Control and Prevention growth charts. A z-score equal to 0 indicates the population mean and larger z-scores are heavier weights and worse outcomes.	Baseline to Month 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite Metabolic Health and Nutrition Measure	As per clinical standards, blood pressure will be measured after 5 minutes of sitting at each patient visit. A minimum of 8-hour fasting total cholesterol, low-density lipoprotein (LDL)-cholesterol, high density lipoprotein (HDL)-cholesterol, triglycerides, glucose, insulin, and glycosylated hemoglobin (HbA1c) will be collected. For HTE analyses the homeostatic model assessment for insulin-resistance (HOMA-IR) will be computed as: (Insulin [IU/mL] x Glucose [mg/dL] /405). Following the modified ATPIII guidelines,130-132 metabolic syndrome is defined when >3 of the following: 1) abdominal obesity (BMI >90%ile, as in NHANES study of metabolic syndrome in youth133; 2) blood pressure >90%ile for height, age, sex; 3) fasting triglycerides >150 mg/dL; 4) low HDL cholesterol (males <40 mg/dL and for females <50 mg/dL); 5) fasting glucose >100 mg/dL Fulfillment of individual criteria and metabolic syndrome will be outcome measures.	Screen/Baseline to Visit 24

Collaborators and Investigators

• Sponsor: Melissa Delbello
• Collaborators: Patient-Centered Outcomes Research Institute
• Investigators: Principal Investigator: Melissa P DelBello, MD, MS, University of Cincinnati

Publications and helpful links

Helpful Links

• US Centers for Disease Control and Prevention growth charts

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (Actual): December 1, 2022
• Study Completion (Actual): June 1, 2023

Study Registration Dates

• First Submitted: July 31, 2015
• First Submitted That Met QC Criteria: August 3, 2015
• First Posted (Estimated): August 5, 2015

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 20, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bipolar and Related Disorders; Mental Disorders; Nutrition Disorders; Overnutrition; Body Weight; Mood Disorders; Overweight; Bipolar Disorder; Physiological Effects of Drugs; Hypoglycemic Agents; Metformin
• Other Study ID Numbers: DelBello PCORI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO