1/2-MC4R Genotype and Pediatric Antipsychotic Drug- Induced Weight Gain

Study Overview
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Brief Summary
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We will conduct a 12-week, randomized open label study, comparing usual care (UC) antipsychotic treatment (aripiprazole, quetiapine, risperidone) with ziprasidone (ZIP) in children and adolescents aged 13-18 years old. Patients will have 10 days or less lifetime antipsychotic exposure and be in clinical need for antipsychotic treatment for a pediatric psychiatric disorder with FDA indication for antipsychotic use, i.e., bipolar mania, schizophrenia-spectrum disorders, and irritability associated with autistic disorder. In addition, we will also include youth fulfilling research diagnostic criteria for severe mood dysregulation (SMD). Randomization will be stratified by high vs. low genetic risk for antipsychotic-induced weight gain based on MC4R genotype and the primary outcome will be weight change from baseline to endpoint between ZIP and UC antipsychotic treatment in each of the two genotype groups. As detailed below, other metabolic and cardiac safety parameters will also be measured and compared across treatments in each of the genotype groups.

Official Title
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1/2-MC4R Genotype and Pediatric Antipsychotic Drug- Induced Weight Gain

Conditions
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High Risk MC4R Genotype, Low Risk MC4R Genotype, One Week or Less Antipsychotic Lifetime Exposure

Intervention / Treatment
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* Drug: Ziprasidone
* Drug: aripiprazole, quetiapine, or risperidone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 13-18 years English-speaking DSM diagnoses that have an FDA indication for SGA use for at least one agent in the respective pediatric or adult age group. Specifically, primary DSM-IV diagnosis of early-onset schizophrenia spectrum disorders; bipolar I disorder mania (and BP-NOS); irritability associated with autism spectrum disorder, as well as severe mood dysregulation (SMD) according to Leibenluft et al. (2011) with an ABC-irritability score of >/=18 Sexually active girls must agree to use two effective forms of birth control or be abstinent Participant has a primary caretaker who has known the child well for at least 6 months before study entry Primary caretaker is able to participate in study appointments Ability of child to participate in all aspects of the protocol per investigator clinical judgment. Exclusion Criteria: Major neurological or medical illnesses that affect weight (e.g., unstable thyroid disease), require a prohibited systemic medication (e.g., diabetes mellitus [insulin], chronic renal failure [steroids); Fasting glucose > 125 mg/dL on 2 occasions during screening Any medication (other than currently prescribed psychotropic medications) that would significantly alter weight Antidepressants not allowed for at least 2 weeks in BP-I or BP-NOS patients DSM-IV diagnosis of anorexia or bulimia nervosa DSM-IV diagnosis of Substance Dependence disorder (other than tobacco dependence) within the past month Initial urine toxicology screen and follow-up screen indicate ongoing use of illicit substance Hypersensitivity to ZIP or UC antipsychotics Pregnant, breast feeding or unwilling to comply with contraceptive requirements Screening or baseline QTc > 450 msec IQ < 55 Significant risk for dangerousness to self or to others Ongoing or previously undisclosed child abuse requiring new department of social service intervention.

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ziprasidone<br>(20-160mg/d, bid) for 12 weeks | Drug: Ziprasidone<br>* random assignment to ZIP (20-160mg/d, bid dosing)<br>* Other names: Geodon;|
| Active Comparator: Aripiprazole, quetiapine, risperidone<br>Aripiprazole (2-30mg/d), Quetiapine (25-800mg/d) or Risperidone (0.1-8mg/d) for 12 weeks | Drug: aripiprazole, quetiapine, or risperidone<br>* random assignement to Usual Care antipsychotic UC antipsychotic (aripiprazole 2-30mg/d, quetiapine 25-800mg/d or risperidone 0.1-8mg/d)<br>* Other names: Abilify, Seroquel, Risperdal;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight Change |  | baseline to week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Weight Change Compared to Baseline Weight |  | baseline to week 12 | 
| BMI Z-scores |  | baseline to week 12 | 
| BMI Percentile |  | baseline to week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MC4R genotype, antipsychotic induced weight gain, pediatric population