Reducing Weight Gain and Improving Metabolic Function in Children Being Treated With Antipsychotics (IMPACT)

This study has been completed.
Sponsor:
Collaborators:
University of Maryland
University of North Carolina, Chapel Hill
The Zucker Hillside Hospital
Information provided by (Responsible Party):
Mark Riddle, MD, Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT00806234
First received: December 9, 2008
Last updated: May 15, 2014
Last verified: May 2014
  Purpose

This study will test the effectiveness of two different treatments for children and adolescents who have gained weight on their antipsychotic medications.


Condition Intervention Phase
Psychotic Disorders
Drug: Aripiprazole or Perphenazine
Drug: Metformin
Drug: Olanzapine, quetiapine, risperidone, ziprasidone, aripiprazole, asenapine, iloperidone, lurasidone, paliperidone, or olanzapine/fluoxetine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Improving Metabolic Parameters of Antipsychotic Child Treatment (IMPACT)

Resource links provided by NLM:


Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:
  • Body mass index (BMI) z-score change [ Time Frame: Measured at Week 24 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Body fat mass [ Time Frame: Measured at Week 24 ] [ Designated as safety issue: Yes ]
  • Whole body insulin sensitivity index [ Time Frame: Measured at Week 24 ] [ Designated as safety issue: Yes ]
  • Triglyceride levels [ Time Frame: Measured at Week 24 ] [ Designated as safety issue: Yes ]
  • Low density lipoprotein (LDL)-cholesterol level [ Time Frame: Measured at Week 24 ] [ Designated as safety issue: Yes ]
  • Metabolic syndrome [ Time Frame: Measured at Week 24 ] [ Designated as safety issue: Yes ]

Enrollment: 127
Study Start Date: January 2009
Study Completion Date: March 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Participants will continue on current antipsychotic medication.
Drug: Olanzapine, quetiapine, risperidone, ziprasidone, aripiprazole, asenapine, iloperidone, lurasidone, paliperidone, or olanzapine/fluoxetine
Current antipsychotic medication will be continued throughout the treatment period, with changes in dose only made as clinically indicated
Other Name: Zyprexa, Seroquel, Risperdal, Geodon, Abilify, Saphris, Sycrest, Fanapt, Fanapta, Zomaril, Latuda, Invega, Symbyax
Experimental: 2
Participants will undergo a staggered switch from current antipsychotic medication to aripiprazole or perphenazine.
Drug: Aripiprazole or Perphenazine
Baseline second generation antipsychotic (SGA) treatment will be gradually decreased and discontinued over 8 weeks while treatment with aripiprazole or perphenazine will be increased to effective levels.
Other Name: Abilify, Trilafon
Experimental: 3
Participants will add metformin to current antipsychotic medication treatment.
Drug: Metformin
Metformin treatment will be added to current SGA treatment, with dosing based on participant weight and increased according to a preset titration schedule unless side effects interfere.
Other Name: Glucophage

Detailed Description:

Disorders that involve severe dysregulation of mood or thoughts in children -- such as early onset bipolar spectrum (BPS) and schizophrenia spectrum (SS) disorders -- are commonly treated with antipsychotic medications. However, many of the newest and most commonly prescribed antipsychotic medications can cause weight gain and metabolic dysfunctions. Use of these newer antipsychotics, called second generation antipsychotics (SGAs), is increasing rapidly in children, and the risk of weight gain from SGAs is higher among children than adults. Excessive weight gain can lead to obesity, which, in turn, can lead to increased health care costs, increased risk of sickness, and lower life expectancy. These factors are enhanced in children and adolescents who grow up obese.

Two different strategies to reduce weight gain and metabolic side effects from SGAs will be tested in this study. The first strategy involves switching from the current SGA to a lower risk agent (aripiprazole or perphenazine) hypothesized to result in weight loss and improved metabolic functioning. The second strategy involves taking the medication metformin in addition to the current SGA. Metformin is approved by the Food and Drug Administration (FDA) to promote weight loss in youth with diabetes and has been effective in reducing weight in youth taking SGAs.

Participation in this study will last between 26 and 27 weeks and will be divided into two parts. The first part will last 2 to 3 weeks and include three study visits. During this part, participants will undergo a physical exam, an electrocardiogram (EKG), a dual energy X-ray absorptiometry (DXA) test, and blood tests. The DXA measures body fat.

The second part will last 24 weeks and include nine study visits. During this part, participants will be randomly assigned to one of three conditions: gradual switch of current SGA medication to either aripiprazole or perphenazine, addition of metformin to current SGA medication, or no change to treatment with current SGA medication. Visits will take place on Weeks 1, 2, 4, 6, 8, 12, 16, 20, and 24. At each visit, participants will meet with a study doctor who will assess symptoms and side effects, and participants and their guardians will receive information and recommendations about childhood obesity and weight loss. There will also be monthly urine pregnancy tests, and two blood tests.

  Eligibility

Ages Eligible for Study:   8 Years to 19 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • DSM diagnoses that have an FDA indication for atypical antipsychotic use for at least one agent in the respective pediatric or adult age group. Specifically, primary DSM-IV diagnosis of Early Onset Schizophrenia Spectrum (EOSS; schizophrenia, schizoaffective disorder, schizophreniform disorder, psychotic disorder NOS); Bipolar Spectrum (bipolar I, II and NOS); Major depressive disorder with psychosis; Mood disorder NOS corresponding to Leibenluft and colleagues severely mood dysregulated (SMD) broad spectrum bipolar disorder; Mood disorder NOS corresponding to irritability associated with autism spectrum disorders; or - for adult teen participants aged 18-19 years - Major depressive disorder. Diagnoses will be determined by clinical interview, Leibenluft's modification of the K-SADS-PL, and the "Aberrant Behavior Checklist" (cutoff score of 18, as used by FDA for approval of risperidone and aripiprazole in minors).
  • Clinically stable on current treatment regimen for at least 30 days, as assessed in a three-step process
  • Current SGA treatment with olanzapine, quetiapine, risperidone, ziprasidone aripiprazole, asenapine, iloperidone, lurasidone, paliperidone, or olanzapine/fluoxetine for ≥ 8 weeks
  • Stable dose of current SGA and psychotropic co-medications for at least 30 days
  • Body mass index (BMI) at least in the 85th percentile for age and gender
  • Substantial weight gain over the previous 3 years while taking a SGA, as reflected by family and referring physician's judgment. The weight gain did not have to occur on the child's current SGA. Weight needs to have remained stable or increased over past year.
  • Agrees to use two effective forms of birth control or to remain abstinent
  • 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 as clinically indicated

Exclusion Criteria:

  • Treatment with any medication (other than the currently prescribed psychotropic medications) that would significantly alter glucose, insulin, or lipid levels. Exception: orlistat and amantadine are permitted if the individual has taken the drug for at least one year without weight loss.
  • Major neurological or medical illness that affects weight gain or that would prevent participation in physical activities
  • Fasting glucose levels indicating need for prompt treatment
  • Pediatrician or pediatric gastroenterologist recommendation to address abnormal fasting labs by pursuing more active treatment than those in the 2007 American Medical Association guidelines
  • Diagnosis of anorexia nervosa or bulimia nervosa, as based on current or lifetime DSM-IV criteria
  • Diagnosis of substance dependence disorder (other than tobacco dependence) within the past month, as based on DSM-IV criteria
  • Positive urine toxicology indicating ongoing use of illicit substance
  • Current treatment with more than one antipsychotic medication
  • Current treatment with more than 3 total psychotropic medications (i.e., 2 psychotropics plus SGA), with the exception of subjects taking 2 medications for ADHD in which a total of 4 psychotropic medications are allowed.
  • Known hypersensitivity to metformin
  • Prior treatment with aripiprazole and perphenazine for more than 2 weeks that was stopped for inefficacy or intolerability
  • Pregnant, breastfeeding, or unwilling to comply with contraceptive requirements of study
  • IQ score less than 55
  • Significant risk of dangerousness to self or to others that would make study participation inadvisable
  • Language issues that prevent child and/or parent from completing assessments or treatment
  • Ongoing or previously undisclosed child abuse requiring new department of social service intervention
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00806234

Locations
United States, Maryland
Johns Hopkins Hospital
Baltimore, Maryland, United States, 21205
University of Maryland
Baltimore, Maryland, United States, 21201
United States, New York
The Zucker Hillside Hospital
Glen Oaks, New York, United States, 11004
United States, North Carolina
University of North Carolina, Division of Child and Adolescent Psychiatry
Chapel Hill, North Carolina, United States, 27599
Sponsors and Collaborators
Johns Hopkins University
University of Maryland
University of North Carolina, Chapel Hill
The Zucker Hillside Hospital
Investigators
Principal Investigator: Gloria Reeves, MD University of Maryland
Principal Investigator: Linmarie Sikich, MD University of North Carolina, Division of Child and Adolescent Psychiatry
Principal Investigator: Christoph Correll, MD The Zucker Hillside Hospital
Principal Investigator: Mark A. Riddle, MD Johns Hopkins University
  More Information

Publications:
Responsible Party: Mark Riddle, MD, Principal Investigator, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT00806234     History of Changes
Other Study ID Numbers: R01 MH080270, R01MH080270, DSIR 84-CTS
Study First Received: December 9, 2008
Last Updated: May 15, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Johns Hopkins University:
Weight Gain
Obesity
IMPACT
Antipsychotic Treatment
Excessive Weight Gain Associated With Antipsychotic Treatment
Hybrid Efficacy/Effectiveness Design
Reducing Weight Gain
Improving Metabolic Parameters
Aripiprazole
Metformin
Risperdal
Seroquel
Quetiapine
Olanzapine
Zyprexa
Geodon
Risperidone
Abilify
Trilafon
Perphenazine
Glucophage
Paliperidone
Olanzapine/fluoxetine

Additional relevant MeSH terms:
Psychotic Disorders
Mental Disorders
Weight Gain
Schizophrenia and Disorders with Psychotic Features
Body Weight Changes
Body Weight
Signs and Symptoms
Fluoxetine
Olanzapine
Perphenazine
Risperidone
Quetiapine
9-hydroxy-risperidone
Aripiprazole
Ziprasidone
Asenapine
Metformin
Antipsychotic Agents
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 26, 2014