Strategies to Reduce Antipsychotic-Associated Weight Gain in Youth

Overview[ - collapse ][ - ]

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.
ConditionWeight Gain
InterventionDrug: metformin
Drug: placebo
PhasePhase 2
SponsorUniversity of North Carolina, Chapel Hill
Responsible PartyUniversity of North Carolina, Chapel Hill
ClinicalTrials.gov IdentifierNCT00617240
First ReceivedFebruary 5, 2008
Last UpdatedFebruary 7, 2014
Last verifiedFebruary 2014

Tracking Information[ + expand ][ + ]

First Received DateFebruary 5, 2008
Last Updated DateFebruary 7, 2014
Start DateJanuary 2007
Estimated Primary Completion DateOctober 2012
Current 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.
Current 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.

Descriptive Information[ + expand ][ + ]

Brief TitleStrategies to Reduce Antipsychotic-Associated Weight Gain in Youth
Official TitleMetformin Mitigation of Atypical Antipsychotic-Induced Metabolic Dysregulation in Adolescent Youth
Brief Summary
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.
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.
Study TypeInterventional
Study PhasePhase 2
Study DesignAllocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention
ConditionWeight Gain
InterventionDrug: metformin
500mg tablets, 250mg to 2000mg/day, po, BID to TID, 26 weeks
Other Names:
GlucophageDrug: placebo
500/0mg tablets, 250-2000mg/day divided BID to TID, po, 26 weeks
Study Arm (s)
  • Experimental: 1
    metformin in doses from 250mg to 2000mg/day for 26 weeks
  • Placebo Comparator: 2
    Matched placebo to metformin, doses between 250/0mg and 2000/0mg per day

Recruitment Information[ + expand ][ + ]

Recruitment StatusCompleted
Estimated Enrollment9
Estimated Completion DateOctober 2012
Estimated Primary Completion DateOctober 2012
Eligibility 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
GenderBoth
Ages10 Years
Accepts Healthy VolunteersNo
ContactsNot Provided
Location CountriesUnited States

Administrative Information[ + expand ][ + ]

NCT Number NCT00617240
Other Study ID Numbers05-2992 GCRC-2501
Has Data Monitoring CommitteeNo
Information Provided ByUniversity of North Carolina, Chapel Hill
Study SponsorUniversity of North Carolina, Chapel Hill
CollaboratorsFoundation of Hope, North Carolina
Investigators Principal Investigator: Linmarie Sikich, MD Unversity of North Carolina, Department of Psychiatry
Verification DateFebruary 2014

Locations[ + expand ][ + ]

University of North Carolina, Department of Psychiatry
Chapel Hill, North Carolina, United States, 27599