1/2-MC4R Genotype and Pediatric Antipsychotic Drug- Induced Weight Gain
Condition: High Risk MC4R Genotype; Low Risk MC4R Genotype; One Week or Less Antipsychotic Lifetime Exposure
MeSH terms: Weight Gain
Intervention: Ziprasidone; aripiprazole, quetiapine, or risperidone
Intervention description: random assignment to ZIP (20-160mg/d, bid dosing); random assignement to Usual Care antipsychotic UC antipsychotic (aripiprazole 2-30mg/d, quetiapine 25-800mg/d or risperidone 0.1-8mg/d)
Intervention MeSH terms: Risperidone; Aripiprazole; Quetiapine Fumarate; Ziprasidone
Phase: Phase 4
Study type: Interventional
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 14.0
Sex: All
Minimum age: 13 Years
Maximum age: 18 Years
Healthy volunteers: No
Keywords: MC4R genotype; antipsychotic induced weight gain; pediatric population

Summary:

      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.
    

Eligibility criteria:

        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.