Clinical trial NCT01844700: 1/2-MC4R Genotype and Pediatric Antipsychotic Drug- Induced Weight Gain
Official title: 1/2-MC4R Genotype and Pediatric Antipsychotic Drug- Induced Weight Gain
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: High Risk MC4R Genotype
Low Risk MC4R Genotype
One Week or Less Antipsychotic Lifetime Exposure
Keywords: MC4R genotype
antipsychotic induced weight gain
pediatric population
Lead sponsor: Northwell Health
Sponsor class: OTHER
First posted: 2013-05-01
Enrollment: 14
Sex: ALL
Minimum age (years): 13
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL

Brief 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.

Primary outcomes:
measure: Weight Change
timeFrame: baseline to week 12
Secondary outcomes:
measure: Percent Weight Change Compared to Baseline Weight
timeFrame: baseline to week 12
measure: BMI Z-scores
timeFrame: baseline to week 12
measure: BMI Percentile
timeFrame: baseline to week 12
Other outcomes:
Locations:
city: Glen Oaks
country: United States
facility: Zucker Hillside Hospital, Psychiatry Research
state: New York
Study officials:
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