Strategies to Reduce Antipsychotic-Associated Weight Gain in Youth (PREVENT)

This study has been completed.
Sponsor:
Collaborator:
Foundation of Hope, North Carolina
Information provided by (Responsible Party):
Linmarie Sikich, MD, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT00617240
First received: February 5, 2008
Last updated: February 7, 2014
Last verified: February 2014
  Purpose

The purpose of this pilot study is to determine whether starting metformin in conjunction with a second-generation antipsychotic (SGA) and providing information about healthy eating and activity will prevent or reduce the amount of weight gain and the metabolic changes in adolescent youth typically seen with second-generation antipsychotic medication.


Condition Intervention Phase
Weight Gain
Drug: metformin
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Metformin Mitigation of Atypical Antipsychotic-Induced Metabolic Dysregulation in Adolescent Youth

Resource links provided by NLM:


Further study details as provided by University of North Carolina, Chapel Hill:

Primary Outcome Measures:
  • Change From Baseline to Week 24 in Body Mass Index (BMI) [ Time Frame: 0-24 weeks ] [ Designated as safety issue: Yes ]
    Change in BMI-Body Mass Index (BMI) is a measure of body fat based on height, weight,gender and chronological age. Change in BMI is calculated as 24 weeks BMI minus the baseline BMI.

  • Change From Baseline to Week 24 in Weight [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
    Change in weight is calculated as 24 weeks weight minus the baseline weight.

  • Change From Baseline to Week 24 in Fat Mass [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
    Fat mass is a measure of excess body fat. Change in Fat Mass is calculated as 24 weeks fat mass minus the baseline fat mass.


Secondary Outcome Measures:
  • Change From Baseline to Week 24 in Insulin Level [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
    Insulin is a peptide hormone and regulates carbohydrate and fat metabolism in the body.Change in Insulin level is calculated as the 24 weeks insulin level minus the baseline insulin level.

  • Change From Baseline to Week 24 in Cholesterol Level [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
    According to the lipid hypothesis, abnormal cholesterol levels are strongly associated with cardiovascular disease because these promote atherosclerosis.Cholesterol levels are measured in milligrams (mg) of cholesterol per deciliter(dL) of blood.Change in cholesterol levels is measured at 24 weeks minus the levels at baseline.

  • Change From Baseline to Week 24 in Triglycerides [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
    In the human body, high levels of triglyceride fats in the bloodstream have been linked to atherosclerosis and, by extension, the risk of heart disease and stroke. A change in triglycerides is calculated from 24 weeks minus baseline levels.

  • Incidence of Metabolic Syndrome [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
    Metabolic syndrome is a combination of the medical disorders that, when co-occurring, increase the risk of developing cardiovascular disease and diabetes.


Enrollment: 9
Study Start Date: January 2007
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
metformin in doses from 250mg to 2000mg/day for 26 weeks
Drug: metformin
500mg tablets, 250mg to 2000mg/day, po, BID to TID, 26 weeks
Other Name: Glucophage
Placebo Comparator: 2
Matched placebo to metformin, doses between 250/0mg and 2000/0mg per day
Drug: placebo
500/0mg tablets, 250-2000mg/day divided BID to TID, po, 26 weeks

Detailed Description:

This is a 24 week, placebo-controlled, random assignment pilot study in which participants will be randomized in a 1:1 ratio to receive either flexible-dose treatment with metformin for 6 months as well as a newly initiated second generation antipsychotic medication or to receive placebo and the newly initiated antipsychotic medication. All subjects will also be provided healthy lifestyle instruction. The study involves monthly visits for the duration of the study. Participants may be treated as inpatients or outpatients throughout the course of the study. Participants will receive a psychiatric evaluation, physical exam, lab work, ECG, medication treatment, and psychiatric care.

The goal is to evaluate the safety and efficacy of means to prevent and treat weight gain and the associated endocrine, metabolic, and inflammatory changes caused by antipsychotic medications. Behavioral treatments to reduce weight gain and metabolic problems after weight gain has occurred have had little impact. Such interventions must be intensive and sustained over months, if not years to be effective. Although basic lifestyle instruction (diet and physical activity) should be the standard of care for all children and adolescents at risk for becoming overweight, pharmacologic interventions may be the best option for substantially augmenting behavioral approaches to weight management.

  Eligibility

Ages Eligible for Study:   10 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects will be between the ages of 10 and 17, male or female, any race or ethnicity
  • Any SPMI pediatric diagnosis that meets DSM-IV criteria and frequently is treated with a SGA- typically but not limited to psychotic, mood, pervasive developmental, oppositional defiant, and conduct disorders
  • SGA-naïve or less than 2 weeks exposure to any SGA, except ziprasidone
  • Legal guardian able and willing to give written informed consent
  • If competent, subject able and willing to assent for their own participation

Exclusion Criteria:

  • Previous trial of metformin
  • Recommendation for treatment with clozapine or ziprasidone
  • Current use of insulin or any oral hypoglycemic agent
  • Current use of a medication known to mitigate weight gain - amantidine, histamine (H2) antagonists (cimetidine, ranitidine, nizatidine), topiramate, orlistat, sibutramine, stimulants (dextroamphetamine, methylphenidate)
  • Any current or past diagnosis of an eating disorder
  • Diabetes mellitus
  • Current active thyroid (TSH >18 microIU/ml; T4 total >18 mcg/dl), hepatic (2 LFTs >4x upper limits of normal), renal (serum Creatinine >1.4 mg/dL in females and serum Creatinine >1.5 mg/dL in males), cardiac, gastrointestinal, or adrenal disease
  • Current substance abuse/dependence within past 2 weeks; a positive urine tox screen at baseline in the absence of meeting criteria for abuse/dependence will not preclude enrollment.
  • Pregnancy or breast feeding
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00617240

Locations
United States, North Carolina
University of North Carolina, Department of Psychiatry
Chapel Hill, North Carolina, United States, 27599
Sponsors and Collaborators
University of North Carolina, Chapel Hill
Foundation of Hope, North Carolina
Investigators
Principal Investigator: Linmarie Sikich, MD Unversity of North Carolina, Department of Psychiatry
  More Information

No publications provided

Responsible Party: Linmarie Sikich, MD, Associate Professor, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT00617240     History of Changes
Other Study ID Numbers: 05-2992 GCRC-2501
Study First Received: February 5, 2008
Results First Received: September 2, 2013
Last Updated: February 7, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by University of North Carolina, Chapel Hill:
antipsychotic
metformin
children
adolescents

Additional relevant MeSH terms:
Weight Gain
Body Weight Changes
Body Weight
Signs and Symptoms
Metformin
Antipsychotic Agents
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Tranquilizing Agents
Central Nervous System Depressants
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs

ClinicalTrials.gov processed this record on August 21, 2014