Metabolic Effects of Antipsychotics in Children

NCT00205699 | Completed Phase 4 Results DMC

• 2 other identifiers: NIMHR01MH072912
• Study Type: interventional
• Target: 144
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Antipsychotic treatment; Insulin action/secretion; Abdominal fat mass, total body fat; Aggression; Resting metabolic rates

Outcome Measures

Primary Outcomes (2)

• Change in DEXA % Body Fat

  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)

  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 Outcomes (4)

• Change in Insulin-stimulated Glycerol Rate of Appearance (Glycerol Ra)

  12 weeks

• Change in Insulin-stimulated Glucose Rate of Appearance (Glucose Ra)

  12 weeks

• Change in MRI-measured Visceral Abdominal Fat

  12 weeks

• Change in MRI-measured Subcutaneous Abdominal Fat

  12 weeks

Study Arms (3)

aripiprazole

ACTIVE COMPARATOR

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

Drug: aripiprazole

olanzapine

ACTIVE COMPARATOR

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

Drug: olanzapine

risperidone

ACTIVE COMPARATOR

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

Drug: risperidone

Interventions

risperidone DRUG

randomized to begin 12 week trial of risperidone

Also known as: Risperdal

risperidone

olanzapine DRUG

randomized to begin 12 week trial of olanzapine

Also known as: Zyprexa

olanzapine

aripiprazole DRUG

randomized to 12 week trial of aripiprazole

Also known as: Abilify

aripiprazole

Eligibility Criteria

• Age: 6 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Washington University School of Medicine, Psychiatry Dept.

St Louis, Missouri, 63110, United States

Location

Related Publications (1)

• 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.

  PMID: 29898210 DERIVED

MeSH Terms

Conditions

Aggression; Oppositional Defiant Disorder; Child Development Disorders, Pervasive; Bipolar Disorder

Interventions

Risperidone; Olanzapine; Aripiprazole

Condition Hierarchy (Ancestors)

Aberrant Motor Behavior in Dementia; Behavioral Symptoms; Behavior; Social Behavior; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders; Bipolar and Related Disorders; Mood Disorders

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Piperazines; Quinolones; Quinolines

Results Point of Contact

• Title: John W. Newcomer
• Organization: Florida Atlantic University

jnewcomer@health.fau.edu

(561) 297-0252

Study Officials

• John W. Newcomer, MD

  Florida Atlantic University and Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

• Ginger Nicol, MD

  Washington University School of Medicine

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2005
• First Posted: September 20, 2005
• Study Start: April 1, 2006
• Primary Completion: March 1, 2011
• Study Completion: July 1, 2011
• Last Updated: June 15, 2018
• Results First Posted: June 15, 2018

Record last verified: 2018-06

Locations

US (1)