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AggressionPhase 4MEACNCT00205699

Metabolic Effects of Antipsychotics in Children

A Phase 4 study testing risperidone, olanzapine and aripiprazole in people with Aggression and Attention Deficit-Hyperactivity, run by Washington University School of Medicine at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 6 to 18 years
What is being tested?
risperidone, olanzapine and aripiprazole
Could I receive a placebo?
No, everyone receives an active treatment
How many people
144 participants
Where
1 siteUnited States
Study dates
Apr 2006to Jul 2011
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 6 to 18 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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

Who cannot join

  • 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;
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  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Washington University School of Medicine, Psychiatry Dept.

    St Louis, Missouri, 63110

Other trials in United States

About this study

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.

Read the 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.

Keywords
Antipsychotic treatment, Insulin action/secretion, Abdominal fat mass, total body fat, Aggression, Resting metabolic rates
Medical subject headings
Aggression, Oppositional Defiant Disorder, Child Development Disorders, Pervasive, Bipolar Disorder

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • risperidoneDrug

    Also called Risperdal

    randomized to begin 12 week trial of risperidone

  • olanzapineDrug

    Also called Zyprexa

    randomized to begin 12 week trial of olanzapine

  • aripiprazoleDrug

    Also called Abilify

    randomized to 12 week trial of aripiprazole

Study groups in NCT00205699
Study groupRoleWhat they receive
aripiprazoleActive comparatorParticipants in this group will be randomized to flexibly-dosed treatment with aripiprazole.
Receives: Drug: aripiprazole
olanzapineActive comparatorParticipants in this group will be randomized to flexibly-dosed treatment with olanzapine.
Receives: Drug: olanzapine
risperidoneActive comparatorParticipants in this group will be randomized to flexibly-dosed treatment with risperidone.
Receives: Drug: risperidone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 12 weeks

  2. 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.

    Measured: 12 weeks

Secondary outcomes (4)

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

    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.

    Measured: 12 weeks

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

    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.

    Measured: 12 weeks

  3. Change in MRI-measured Visceral Abdominal Fat

    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.

    Measured: 12 weeks

  4. Change in MRI-measured Subcutaneous Abdominal Fat

    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.

    Measured: 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Sep 2005 (estimated)
  2. Study startApr 2006
  3. Primary completionMar 2011
  4. Study completionJul 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
144 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00205699
Sponsor's protocol ID
NIMH
Other IDs
R01MH072912
Acronym
MEAC
Status last verified
Jun 2018
First submitted
13 Sep 2005
Last updated
15 Jun 2018
Data monitoring committee
Yes
Individual data sharing
Undecided

Publications

  • 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.

    PubMed 29898210

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing risperidone, olanzapine and aripiprazole in people with Aggression and Attention Deficit-Hyperactivity, run by Washington University School of Medicine at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Jun 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in DEXA % Body Fat (time frame: 12 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00205699, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2018.

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