Reducing Weight Gain and Improving Metabolic Function in Children Being Treated With Antipsychotics - Full Text View

Sponsor:	National Institute of Mental Health (NIMH)
Information provided by:	National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier:	NCT00806234

Purpose

This study will test the effectiveness of two different treatments for children and adolescents who have gained weight on their antipsychotic medications.

Condition	Intervention	Phase
Psychotic Disorders	Drug: Aripiprazole Drug: Metformin Drug: Olanzapine, quetiapine, or risperidone	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Factorial Assignment Masking: Single Blind (Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Improving Metabolic Parameters of Antipsychotic Child Treatment

Resource links provided by NLM:

MedlinePlus related topics: Child Mental Health Diabetes Medicines Mental Disorders Psychotic Disorders

Drug Information available for: Risperidone Quetiapine Quetiapine fumarate Aripiprazole Olanzapine Metformin Metformin hydrochloride

U.S. FDA Resources

Further study details as provided by National Institute of Mental Health (NIMH):

Primary Outcome Measures:

Body mass index (BMI) z-score change [ Time Frame: Measured at Week 24 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Body fat mass [ Time Frame: Measured at Week 24 ] [ Designated as safety issue: Yes ]
Whole body insulin sensitivity index [ Time Frame: Measured at Week 24 ] [ Designated as safety issue: Yes ]
Triglyceride levels [ Time Frame: Measured at Week 24 ] [ Designated as safety issue: Yes ]
Low density lipoprotein (LDL)-cholesterol level [ Time Frame: Measured at Week 24 ] [ Designated as safety issue: Yes ]
Metabolic syndrome [ Time Frame: Measured at Week 24 ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	240
Study Start Date:	January 2009
Estimated Study Completion Date:	June 2013
Estimated Primary Completion Date:	January 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 1 Participants will continue on current antipsychotic medication.	Drug: Olanzapine, quetiapine, or risperidone Current antipsychotic medication will be continued throughout the treatment period, with changes in dose only made as clinically indicated Other Name: Zyprexa, Seroquel, Risperdal
Experimental: 2 Participants will undergo a staggered switch from current antipsychotic medication to aripiprazole.	Drug: Aripiprazole Baseline second generation antipsychotic (SGA) treatment will be gradually decreased and discontinued over 8 weeks while treatment with aripiprazole will be increased to effective levels. Other Name: Abilify
Experimental: 3 Participants will add metformin to current antipsychotic medication treatment.	Drug: Metformin Metformin treatment will be added to current SGA treatment, with dosing based on participant weight and increased according to a preset titration schedule unless side effects interfere. Other Name: Glucophage

Detailed Description:

Early onset bipolar spectrum (BPS) and schizophrenia spectrum (SS) disorders are those that involve severe dysregulation of mood or thoughts, sometimes including delusions and hallucinations. These debilitating symptoms are often experienced by children and adolescents with BPS and SS. BPS and SS disorders are commonly treated with antipsychotic medications, but many of the newest and most commonly prescribed antipsychotic medications can cause weight gain and metabolic dysfunctions. Use of these newer antipsychotics, called second generation antipsychotics (SGAs), is increasing rapidly in children, and the risk of weight gain from SGAs is higher among children than adults. Excessive weight gain can lead to obesity, which, in turn, can lead to increased health care costs, increased risk of sickness, and lower life expectancy. These factors are enhanced in children and adolescents who grow up obese.

Two different strategies to reduce weight gain and metabolic side effects from SGAs will be tested in this study. The first strategy involves switching from the current SGA to aripiprazole, another antipsychotic found to result in weight loss and improved metabolic functioning. The second strategy involves taking the medication metformin in addition to the current SGA. Metformin is approved by the Food and Drug Administration (FDA) to promote weight loss in youth with diabetes and has been effective in reducing weight in youth taking SGAs.

Participation in this study will last between 26 and 27 weeks and will be divided into three parts. The first part will last 2 to 3 weeks and include three study visits. During this part, participants will undergo a physical exam, an electrocardiogram (EKG), a dual energy X-ray absorptiometry (DXA) test, a blood test, and a glucose tolerance test (GTT). The DXA measures body fat, and the GTT measures the body's ability to process glucose.

The second part will last 12 weeks and include six study visits. During this part, participants will be randomly assigned to one of three conditions: gradual switch of current SGA medication to the SGA aripiprazole, addition of metformin to current SGA medication, or no change to treatment with current SGA medication. Visits will take place on Weeks 1, 2, 4, 6, 8, and 12. At each visit, participants will meet with a study doctor who will assess symptoms and side effects, and participants and their guardians will receive information and recommendations about childhood obesity and weight loss. This part of the study will also include two blood tests, two GTT tests, three clinical assessments, and three urine pregnancy tests.

The third part will last 12 weeks and involve three study visits, which will come on Weeks 16, 20, and 24. During this part, participants will have their health monitored to determine longer term consequences of their continuing treatment. At each visit, participants will undergo a doctor's visit, a clinical assessment, and a urine pregnancy test. On the final visit, participants will also undergo a blood test and a GTT test.

Eligibility

Ages Eligible for Study:	8 Years to 17 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Primary diagnosis of early onset schizophrenia spectrum (EOSS) disorder or bipolar spectrum (BPS) disorder, as determined by DSM-IV criteria, Leibenluft's criteria, Leibenluft's modification of the K-SADS-PL, and clinical interview
Clinically stable on current treatment regimen for at least 30 days, as assessed in a three-step process
Current SGA treatment with olanzapine, quetiapine, or risperidone for at least 8 weeks
Stable dose of current SGA and psychotropic co-medications for at least 30 days
Body mass index (BMI) at least in the 85th percentile for age and gender
Significant weight gain over the previous 12 months while taking the current SGA
Agrees to use two effective forms of birth control or to remain abstinent
Has a primary caretaker who has known the child well for at least 6 months before study entry
Primary caretaker is able to participate in study appointments as clinically indicated

Exclusion Criteria:

Treatment with any medication (other than the currently prescribed psychotropic medications) that would significantly alter glucose, insulin, or lipid levels
Major neurological or medical illness that affects weight gain or that would prevent participation in physical activities
Fasting glucose levels indicating need for prompt treatment
Pediatrician recommendation to address abnormal fasting labs by pursuing more active treatment than those in the 2007 American Medical Association guidelines
Diagnosis of autism, Asperger's disorder, anorexia nervosa, or bulimia nervosa, as based on current or lifetime DSM-IV criteria
Diagnosis of substance dependence disorder (other than tobacco dependence) within the past month, as based on DSM-IV criteria
Positive urine toxicology indicating ongoing use of illicit substance
Current treatment with more than one antipsychotic medication
Current treatment with more than three total psychotropic medications
Known hypersensitivity to aripiprazole or metformin
Prior inadequate clinical response to an adequate trial of aripiprazole
Pregnant, breastfeeding, or unwilling to comply with contraceptive requirements of study
IQ score less than 70
Significant risk of dangerousness to self or to others that would make study participation inadvisable
Language issues that prevent child and/or parent from completing assessments or treatment
Ongoing or previously undisclosed child abuse requiring new department of social service intervention

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00806234

Contacts

Contact: Mark A. Riddle, MD		mriddle@jhmi.edu
Contact: Courtney Keeton, PhD	410-614-5174	cpierce@jhmi.edu

Locations

United States, Maryland
Johns Hopkins Hospital	Recruiting
Baltimore, Maryland, United States, 21205
Contact: Courtney Keeton, PhD 410-614-5174 cpierce@jhmi.edu
Principal Investigator: Mark A. Riddle, MD
University of Maryland	Recruiting
Baltimore, Maryland, United States, 21201
Contact: Kristin Bussell, CNRP-PMH 410-328-9087 kbussell@psych.umaryland.edu
Principal Investigator: Gloria Reeves, MD
United States, New York
The Zucker Hillside Hospital	Recruiting
Glen Oaks, New York, United States, 11004
Contact: Eva Schenk, MD 718-470-4391 eschenk@nshs.edu
Contact: Sandeep Kapoor, MD 718-470-8751 skapoor@nshs.edu
Principal Investigator: Christoph Correll, MD
United States, North Carolina
University of North Carolina, Division of Child and Adolescent Psychiatry	Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Madeline Puglia, BA 800-708-0048 aspire@unc.edu
Principal Investigator: Linmarie Sikich, MD

Sponsors and Collaborators

National Institute of Mental Health (NIMH)

Investigators

Principal Investigator:	Gloria Reeves, MD	University of Maryland
Principal Investigator:	Linmarie Sikich, MD	University of North Carolina, Division of Child and Adolescent Psychiatry
Principal Investigator:	Christoph Correll, MD	The Zucker Hillside Hospital
Principal Investigator:	Mark A. Riddle, MD	Johns Hopkins University

More Information

No publications provided

Responsible Party:	Mark A. Riddle, MD, Johns Hopkins University
ClinicalTrials.gov Identifier:	NCT00806234 History of Changes
Other Study ID Numbers:	R01 MH080270, DSIR 84-CTS
Study First Received:	December 9, 2008
Last Updated:	April 16, 2009
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Institute of Mental Health (NIMH):

Antipsychotic Treatment
Excessive Weight Gain Associated With Antipsychotic Treatment
Hybrid Efficacy/Effectiveness Design
Reducing Weight Gain

Improving Metabolic Parameters
Aripiprazole
Metformin

Additional relevant MeSH terms:

Psychotic Disorders
Mental Disorders
Weight Gain
Schizophrenia and Disorders with Psychotic Features
Body Weight Changes
Body Weight
Signs and Symptoms
Metformin
Antipsychotic Agents
Risperidone
Quetiapine
Olanzapine
Aripiprazole
Hypoglycemic Agents
Physiological Effects of Drugs

Pharmacologic Actions
Tranquilizing Agents
Central Nervous System Depressants
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Dopamine Antagonists
Dopamine Agents
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Antiemetics

ClinicalTrials.gov processed this record on February 09, 2012