| City: |
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St. Louis |
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State:
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MO |
| Zip Code: |
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63110 |
| Conditions: |
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Aggression - ADHD - Oppositional Defiant Disorder - PDD - Bipolar Disorder |
| Purpose: |
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The prevalence of overweight and obesity, insulin resistance, hyperglycemia, dyslipidemia
and type 2 diabetes mellitus (T2DM) are increasing in children. Increased adiposity and
related reductions in insulin sensitivity are major risk factors for the development of
hyperglycemia, dyslipidemia, T2DM, and cardiovascular disease. Reductions in lifespan
attributable to obesity impact younger individuals most measurably. Antipsychotic
medications are extensively used in children, with certain agents producing greater
increases in weight and adiposity than other commonly used drugs in this age group.
Increased use of atypical antipsychotics in children has been stimulated by reported
efficacy for behaviors such as aggression that can occur in a variety of disorders. However,
no previous randomized clinical trial has sensitively quantified the metabolic effects of
widely used atypical antipsychotics. This study would address clinically relevant questions
concerning both the safety and efficacy of these agents in antipsychotic-naïve aggressive
children with conduct disorder, with permitted co-morbidity for a variety of psychiatric
conditions including attention deficit disorder, bipolar disorder, high functioning
pervasive developmental disorder, autism and schizophrenia. 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,
insulin secretion, abdominal fat mass, total body and fat-free mass, resting metabolic
rates, 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, area-under-the-curve for
post-load insulin and c-peptide during frequently sampled oral glucose tolerance tests, body
composition with dual energy x-ray absorptiometry and magnetic resonance imaging (MRI),
indirect calorimetry and standardized assessments of efficacy and adverse events. Treatment
effects will primarily be analyzed using repeated measures analysis of covariance (ANCOVA),
controlling for baseline adiposity and other key risk variables. Relevant data are
critically needed to target clinical therapy and basic research, identify medical risks, and
guide regulatory decisions in this vulnerable population.
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| Study summary: |
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The proposed randomized clinical trial aims to assess 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 (Zyprexa), risperidone (Risperdal) or aripiprazole (Abilify).
Aim 1: To evaluate effects of selected antipsychotic treatments on insulin action in
skeletal muscle (glucose disposal), liver (glucose production) and adipose tissue
(lipolysis).
Aim 2: To evaluate effects of selected antipsychotic treatments on insulin secretion.
Aim 3: To evaluate effects of selected antipsychotic treatments on abdominal fat mass, total
body fat and total fat-free mass.
Aim 4: To evaluate effects of selected antipsychotic treatments on resting metabolic rates
(carbohydrate and fat oxidation).
Aim 5: To evaluate effects of selected antipsychotic treatments on efficacy for symptoms of
aggression.
Important secondary aims include the assessment of non-metabolic adverse events, and the
assessment of each antipsychotic treatment condition in children with and without
concomitant stimulant therapy. Reduced adverse metabolic effects are hypothesized during
concomitant stimulant therapy. Children aged 7-18 will be studied, exploring age-related
differences in vulnerability to treatment-induced adverse metabolic changes. Finally,
treatment effects on regulatory hormones, including cortisol, glucagon, leptin, ghrelin and
adiponectin will be explored. This will allow the assessment of possible confounds to the
interpretation of the primary hypotheses. It will also permit the generation of additional
hypotheses concerning mechanisms contributing to drug-induced changes in weight and fat
mass. Relevant data on the primary and secondary aims are critically needed to assess the
risks as well as benefits of clinical therapy in children, to identify needs for additional
basic research, as well as to guide administrative and regulatory decision-making. |
| Criteria: |
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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. |
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If you are interested in this clinical trial please use the contact information above. If you would like to get additional information about this clinical trial please visit ClinicalTrials.gov.
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| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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February 17, 2011 |
Modifications to
this listing: |
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Only selected fields are shown, please use the link
above to view all information about this clinical trial. |
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