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.
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
144
randomized to begin 12 week trial of risperidone
randomized to begin 12 week trial of olanzapine
randomized to 12 week trial of aripiprazole
Washington University School of Medicine, Psychiatry Dept.
St Louis, Missouri, United States
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.
Time frame: 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.
Time frame: 12 weeks
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.
Time frame: 12 weeks
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.
Time frame: 12 weeks
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.
Time frame: 12 weeks
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.
Time frame: 12 weeks
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