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Metabolic Effects of Antipsychotics in Children (MEAC)

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ClinicalTrials.gov Identifier: NCT00205699
Recruitment Status : Completed
First Posted : September 20, 2005
Results First Posted : June 15, 2018
Last Update Posted : June 15, 2018
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Washington University School of Medicine

Study Description
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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.

Condition or disease Intervention/treatment Phase
Aggression Attention Deficit-Hyperactivity Oppositional Defiant Disorder Pervasive Development Disorders Bipolar Disorder Drug: risperidone Drug: olanzapine Drug: aripiprazole Phase 4

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 144 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Metabolic Effects of Antipsychotics in Children
Actual Study Start Date : April 2006
Actual Primary Completion Date : March 2011
Actual Study Completion Date : July 2011

Resource links provided by the National Library of Medicine


Arms and Interventions
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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 Name: 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 Name: 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 Name: Risperdal


Outcome Measures
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Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   6 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00205699


Locations
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United States, Missouri
Washington University School of Medicine, Psychiatry Dept.
Saint Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
National Institute of Mental Health (NIMH)
Investigators
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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
  Study Documents (Full-Text)

Documents provided by Washington University School of Medicine:
Informed Consent Form: Child and Adult Consent  [PDF] October 18, 2010
Informed Consent Form: Genetics Consent  [PDF] September 30, 2010
Study Protocol  [PDF] March 22, 2018
Statistical Analysis Plan  [PDF] March 28, 2018

More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00205699    
Other Study ID Numbers: NIMH
R01MH072912 ( U.S. NIH Grant/Contract )
First Posted: September 20, 2005    Key Record Dates
Results First Posted: June 15, 2018
Last Update Posted: June 15, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by Washington University School of Medicine:
Antipsychotic treatment
Insulin action/secretion
Abdominal fat mass, total body fat
Aggression
Resting metabolic rates
Additional relevant MeSH terms:
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Disease
Bipolar Disorder
Aggression
Attention Deficit and Disruptive Behavior Disorders
Child Development Disorders, Pervasive
Autism Spectrum Disorder
Pathologic Processes
Neurodevelopmental Disorders
Mental Disorders
Bipolar and Related Disorders
Behavioral Symptoms
Olanzapine
Risperidone
Aripiprazole
Serotonin Antagonists
 Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Dopamine Antagonists
Dopamine Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Serotonin Uptake Inhibitors