Metabolic Effects of Antipsychotics in Children (MEAC)

June 13, 2018 updated by: Washington University School of Medicine
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

144

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine, Psychiatry Dept.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 years to 18 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: SINGLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: aripiprazole
Participants in this group will be randomized to flexibly-dosed treatment with aripiprazole.
Drug: aripiprazole
randomized to 12 week trial of aripiprazole
Other Names:
  • Abilify
ACTIVE_COMPARATOR: olanzapine
Participants in this group will be randomized to flexibly-dosed treatment with olanzapine.
Drug: olanzapine
randomized to begin 12 week trial of olanzapine
Other Names:
  • Zyprexa
ACTIVE_COMPARATOR: risperidone
Participants in this group will be randomized to flexibly-dosed treatment with risperidone.
Drug: risperidone
randomized to begin 12 week trial of risperidone
Other Names:
  • Risperdal

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in DEXA % Body Fat
Time Frame: 12 weeks
This study hypothesized that antipsychotic treatment would increase percent total body fat, as measured by whole body dual energy x-ray absorptiometry (DEXA), with larger adverse effects for olanzapine.
12 weeks
Change in Insulin-stimulated Glucose Rate of Disappearance (Glucose Rd)
Time Frame: 12 weeks
This study hypothesized that antipsychotic treatment would decrease insulin sensitivity at muscle, as measured by the insulin-stimulated rate of disappearance of glucose (glucose Rd), with larger adverse effects for olanzapine.
12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Insulin-stimulated Glycerol Rate of Appearance (Glycerol Ra)
Time Frame: 12 weeks
This study hypothesized that antipsychotic treatment would decrease insulin sensitivity at adipose tissue, as measured by the insulin-stimulated rate of disappearance of glycerol (glycerol Ra), with larger adverse effects for olanzapine.
12 weeks
Change in Insulin-stimulated Glucose Rate of Appearance (Glucose Ra)
Time Frame: 12 weeks
This study hypothesized that antipsychotic treatment would decrease hepatic insulin sensitivity, as measured by the rate of appearance of glucose (glucose Ra), with larger adverse effects for olanzapine.
12 weeks
Change in MRI-measured Visceral Abdominal Fat
Time Frame: 12 weeks
This study hypothesized that antipsychotic treatment would increase visceral abdominal fat, as measured by abdominal magnetic resonance imaging (MRI), with larger adverse effects for olanzapine.
12 weeks
Change in MRI-measured Subcutaneous Abdominal Fat
Time Frame: 12 weeks
This study hypothesized that antipsychotic treatment would increase subcutaneous abdominal fat, as measured by abdominal magnetic resonance imaging (MRI), with larger adverse effects for olanzapine.
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Washington University School of Medicine

Collaborators

National Institute of Mental Health (NIMH)

Investigators

  • Principal Investigator: John W. Newcomer, MD, Florida Atlantic University and Washington University School of Medicine
  • Study Director: Ginger Nicol, MD, Washington University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

April 1, 2006

Primary Completion (ACTUAL)

March 1, 2011

Study Completion (ACTUAL)

July 1, 2011

Study Registration Dates

First Submitted

September 13, 2005

First Submitted That Met QC Criteria

September 13, 2005

First Posted (ESTIMATE)

September 20, 2005

Study Record Updates

Last Update Posted (ACTUAL)

June 15, 2018

Last Update Submitted That Met QC Criteria

June 13, 2018

Last Verified

June 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NIMH
  • R01MH072912 (NIH)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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