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

Phase 4

Completed

• Conditions: Bipolar Disorder
• Interventions: Drug: Metformin; Behavioral: healthy lifestyle intervention (LIFE)

• Registration Number: NCT02515773
• Lead Sponsor: Melissa Delbello

Brief Summary

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.

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 Timeline

• Study First Submitted: 2015-07-31
• Study First Submitted QC: 2015-08-03
• Study First Posted: 2015-08-05
• Study Start: 2015-12
• Primary Completion: 2022-12
• Study Completion: 2023-06
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-19
• Last Update Posted: 2023-09-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1565

Inclusion Criteria

Not provided

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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;

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MET and LIFE	healthy lifestyle intervention (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.
Healthy lifestyle intervention (LIFE)	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).
MET and LIFE	Metformin	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.

Primary Outcome Measures

Name	Time	Method
BMI z-score	Screen/Baseline to Visit 24	BMI z-score will be computed from measurement of height and weight. Raw BMI is calculated as (weight(kg)/ height(m)2). Normalized BMI (z-score, adjusted for age and sex), will be calculated using the program provided by the USDA/ARS Children's Nutrition Research Center at Baylor College of Medicine (http://www.bcm.edu/cnrc/bodycomp/bmiz2.html). At each site weight will be measured with a Seca scale, model 882, calibrated to the nearest 0.2 kg per manufacturer instructions at intervals not to exceed 2 months using standard weights.

Secondary Outcome Measures

Name	Time	Method
Composite Metabolic Health and Nutrition Measure	Screen/Baseline to Visit 24	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.

Trial Locations

Locations (29)

Ohio State University; 🇺🇸 Columbus, Ohio, United States

Children's Home; 🇺🇸 Cincinnati, Ohio, United States

Cincinnati Children's Hospital Medical Center; 🇺🇸 Cincinnati, Ohio, United States

St. Aloysius; 🇺🇸 Cincinnati, Ohio, United States

University Hospital Medical Center Cleveland; 🇺🇸 Cleveland, Ohio, United States

Maimonides; 🇺🇸 Brooklyn, New York, United States

South Oaks; 🇺🇸 Amityville, New York, United States

Jersey Shore Medical Center; 🇺🇸 Neptune, New Jersey, United States

The Children's Home of Northern Kentucky; 🇺🇸 Covington, Kentucky, United States

SUNY Downstate/ Kings County Hospital; 🇺🇸 Brooklyn, New York, United States

Northwell Zucker Long Island Jewish Hospital; 🇺🇸 Glen Oaks, New York, United States

Mount Sinai; 🇺🇸 New York, New York, United States

NYCCC; 🇺🇸 Brooklyn, New York, United States

LIJ Zucker Hillside Hospital; 🇺🇸 New York, New York, United States

NorthShore Child and Family Guidance; 🇺🇸 Roslyn Heights, New York, United States

Lighthouse Youth Services; 🇺🇸 Cincinnati, Ohio, United States

Child Center of New York,; 🇺🇸 Queens, New York, United States

Central Clinic; 🇺🇸 Cincinnati, Ohio, United States

StonyBrook; 🇺🇸 Stony Brook, New York, United States

Talbert House; 🇺🇸 Cincinnati, Ohio, United States

Resident Mood Medication Clinic; 🇺🇸 Cincinnati, Ohio, United States

St. Joseph's Orphanage; 🇺🇸 Cincinnati, Ohio, United States

Child Focus; 🇺🇸 Cincinnati, Ohio, United States

NECCO; 🇺🇸 Cincinnati, Ohio, United States

Nationwide Children's Hospital Columbus; 🇺🇸 Columbus, Ohio, United States

TCN Family Solutions; 🇺🇸 Xenia, Ohio, United States

South Community; 🇺🇸 Dayton, Ohio, United States

Butler Behavioral Health Services; 🇺🇸 Hamilton, Ohio, United States

Seton Family of Hospitals; 🇺🇸 Austin, Texas, United States