Metabolic Effects of Antipsychotics in Children

NCT ID: NCT00205699

Last Updated: 2018-06-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 144 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-04-30
• Study Completion Date: 2011-07-31

Brief Summary

The project aims to describe and compare the outcome of 12 weeks of prospective, randomized treatment with olanzapine, risperidone or aripiprazole on insulin action in skeletal muscle, liver and adipose tissue, abdominal fat mass, total body and fat-free mass, efficacy for symptoms of aggression and non-metabolic adverse events. Children aged 6-18 will be studied, exploring effects of stimulant therapy and age-related differences in vulnerability to treatment-induced adverse metabolic changes. Aims are addressed by measuring glucose and lipid kinetics with stable isotope tracers, body composition with dual energy x-ray absorptiometry and magnetic resonance imaging (MRI), and standardized assessments of efficacy and adverse events. Relevant data are critically needed to target clinical therapy and basic research, identify medical risks, and guide regulatory decisions in this vulnerable population.

Detailed Description

This randomized clinical trial assesses both the safety and efficacy of atypical antipsychotic agents in antipsychotic-naive aggressive children with various childhood psychiatric disorders during 12 weeks of prospective, randomized treatment with olanzapine, risperidone or aripiprazole.

Aim 1: To evaluate effects of selected antipsychotic treatments on insulin action in muscle (glucose disposal), liver (glucose production) and adipose tissue (lipolysis).

Aim 2: To evaluate effects of selected antipsychotic treatments on abdominal fat mass, total body fat and total fat-free mass.

Conditions

Aggression; Attention Deficit-Hyperactivity; Oppositional Defiant Disorder; Pervasive Development Disorders; Bipolar Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

aripiprazole

Participants in this group will be randomized to flexibly-dosed treatment with aripiprazole.

Group Type: ACTIVE_COMPARATOR

aripiprazole

Intervention Type: DRUG

randomized to 12 week trial of aripiprazole

olanzapine

Participants in this group will be randomized to flexibly-dosed treatment with olanzapine.

Group Type: ACTIVE_COMPARATOR

olanzapine

Intervention Type: DRUG

randomized to begin 12 week trial of olanzapine

risperidone

Participants in this group will be randomized to flexibly-dosed treatment with risperidone.

Group Type: ACTIVE_COMPARATOR

risperidone

Intervention Type: DRUG

randomized to begin 12 week trial of risperidone

Interventions

risperidone

randomized to begin 12 week trial of risperidone

Intervention Type: DRUG

olanzapine

randomized to begin 12 week trial of olanzapine

Intervention Type: DRUG

aripiprazole

randomized to 12 week trial of aripiprazole

Intervention Type: DRUG

Other Intervention Names

Risperdal; Zyprexa; Abilify

Eligibility Criteria

Inclusion Criteria

• Aged 6-18 years
• Generally healthy and a score of ≥ 18 on the Aberrant Behavior Checklist in the context of one or more Axis I Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) childhood psychiatric disorders, including conduct disorder, oppositional defiant disorder, disruptive behavior disorder, autism, pervasive developmental disorder, attention deficit disorder, schizophrenia and bipolar affective disorders
• Children's Global Assessment Scale (CGAS) score ≤ 60
• Not previously treated with an antipsychotic; individual subjects with remote, brief prior antipsychotic exposure may be considered for enrollment by the PI on a case by case basis
• Patient assent and informed consent obtained from the parent or guardian
• No clinically significant (based on PI determination) changes in permitted medications (e.g., stimulants and selective serotonin reuptake inhibitors [SSRIs]) for approximately 1 month prior to Baseline evaluations

Exclusion Criteria

• Active suicidality or primary dx of major depressive disorder
• Any lifetime use of antipsychotics or non-serotonin selective reuptake inhibitor (non-SSRI) anti-depressants
• The presence of any serious medical disorder, based on PI determination, that may confound the assessment of relevant biologic measures or diagnoses, including:

• significant organ system dysfunction;
• endocrine disease, including type 1 or type 2 diabetes mellitus;
• coagulopathy;
• anemia;
• or acute infection.
• Subjects regularly taking any glucose lowering agent, lipid lowering agent, exogenous testosterone, recombinant human growth hormone, or any other endocrine agent that might confound substrate metabolism, oral glucocorticoids (glucocorticoid inhalants and nasal sprays are permitted), antihistamines, sedating antihistamines (non-sedating antihistamines such as but not limited to Claritin (loratadine) and Zyrtec (cetirizine) are permitted), and certain mood stabilizing agents, as some medications may themselves worsen or otherwise alter weight gain, glucose and lipid regulation or otherwise make it difficult to assess the effects of the antipsychotic alone; (note that exposure to many psychotropic agents including stimulants and SSRI's is permitted in order to maintain the generalizability of the sample);
• Intelligence quotient (IQ) < 70 (based on school records and/or evaluation by clinician)
• current substance abuse
• Past history or currently has dyskinesia
• Stimulant dosage significantly higher (per PI judgment)than the equivalent of approximately 2mg/kg/day methylphenidate equivalent dose.

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John W. Newcomer, MD

Role: PRINCIPAL_INVESTIGATOR

Florida Atlantic University and Washington University School of Medicine

Ginger Nicol, MD

Role: STUDY_DIRECTOR

Washington University School of Medicine

Locations

Washington University School of Medicine, Psychiatry Dept.

St Louis, Missouri, United States

Countries

United States

References

Nicol GE, Yingling MD, Flavin KS, Schweiger JA, Patterson BW, Schechtman KB, Newcomer JW. Metabolic Effects of Antipsychotics on Adiposity and Insulin Sensitivity in Youths: A Randomized Clinical Trial. JAMA Psychiatry. 2018 Aug 1;75(8):788-796. doi: 10.1001/jamapsychiatry.2018.1088.

Reference Type: DERIVED

PMID: 29898210 (View on PubMed)

Provided Documents

Document Type: Informed Consent Form: Child and Adult Consent

View Document

Document Type: Informed Consent Form: Genetics Consent

View Document

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

R01MH072912

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NIMH

Identifier Type: -

Identifier Source: org_study_id