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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01844700
Recruitment Status : Terminated (very slow recruitment, no sufficient results)
First Posted : May 1, 2013
Results First Posted : February 5, 2016
Last Update Posted : February 5, 2016
Information provided by (Responsible Party):
Anil K. Malhotra, Northwell Health

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.

Condition or disease Intervention/treatment Phase
High Risk MC4R Genotype Low Risk MC4R Genotype One Week or Less Antipsychotic Lifetime Exposure Drug: Ziprasidone Drug: aripiprazole, quetiapine, or risperidone Phase 4

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 14 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Official Title: 1/2-MC4R Genotype and Pediatric Antipsychotic Drug- Induced Weight Gain
Study Start Date : July 2013
Actual Primary Completion Date : April 2014
Actual Study Completion Date : April 2014

Arm Intervention/treatment
Active Comparator: Ziprasidone
(20-160mg/d, bid) for 12 weeks
Drug: Ziprasidone
random assignment to ZIP (20-160mg/d, bid dosing)
Other Name: Geodon

Active Comparator: Aripiprazole, quetiapine, risperidone
Aripiprazole (2-30mg/d), Quetiapine (25-800mg/d) or Risperidone (0.1-8mg/d) for 12 weeks
Drug: aripiprazole, quetiapine, or risperidone
random assignement to Usual Care antipsychotic UC antipsychotic (aripiprazole 2-30mg/d, quetiapine 25-800mg/d or risperidone 0.1-8mg/d)
Other Name: Abilify, Seroquel, Risperdal

Primary Outcome Measures :
  1. Weight Change [ Time Frame: baseline to week 12 ]

Secondary Outcome Measures :
  1. Percent Weight Change Compared to Baseline Weight [ Time Frame: baseline to week 12 ]
  2. BMI Z-scores [ Time Frame: baseline to week 12 ]
  3. BMI Percentile [ Time Frame: baseline to week 12 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   13 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01844700

United States, New York
Zucker Hillside Hospital, Psychiatry Research
Glen Oaks, New York, United States, 11004
Sponsors and Collaborators
Northwell Health

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Responsible Party: Anil K. Malhotra, Director, Psychiatric Research, Northwell Health Identifier: NCT01844700     History of Changes
Other Study ID Numbers: 12-403A
First Posted: May 1, 2013    Key Record Dates
Results First Posted: February 5, 2016
Last Update Posted: February 5, 2016
Last Verified: January 2016

Keywords provided by Anil K. Malhotra, Northwell Health:
MC4R genotype
antipsychotic induced weight gain
pediatric population

Additional relevant MeSH terms:
Weight Gain
Body Weight Changes
Body Weight
Signs and Symptoms
Antipsychotic Agents
Quetiapine Fumarate
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Dopamine Antagonists
Dopamine Agents