Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Improving Metabolic Parameters of Antipsychotic Child Treatment With Ziprasidone, Aripiprazole, and Clozapine (ZAC)

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.
 
ClinicalTrials.gov Identifier: NCT00617058
Recruitment Status : Terminated (Terminated in lieu of similar,competing large, multi-site study.)
First Posted : February 15, 2008
Results First Posted : December 31, 2012
Last Update Posted : December 31, 2012
Sponsor:
Collaborator:
Foundation of Hope, North Carolina
Information provided by (Responsible Party):
Linmarie Sikich, MD, University of North Carolina, Chapel Hill

Tracking Information
First Submitted Date  ICMJE February 5, 2008
First Posted Date  ICMJE February 15, 2008
Results First Submitted Date  ICMJE October 29, 2012
Results First Posted Date  ICMJE December 31, 2012
Last Update Posted Date December 31, 2012
Study Start Date  ICMJE March 2007
Actual Primary Completion Date June 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 28, 2012)
  • Percent Change in BMI [ Time Frame: 24 weeks ]
  • Absolute Change in Weight [ Time Frame: 24 weeks ]
  • Percent Change in Fat Mass [ Time Frame: 24 weeks ]
  • Percent Change in Weight [ Time Frame: 24 weeks ]
Original Primary Outcome Measures  ICMJE
 (submitted: February 14, 2008)
  • BMI change [ Time Frame: 26 weeks ]
  • Weight change [ Time Frame: 26 weeks ]
  • Fat mass [ Time Frame: 26 weeks ]
Change History Complete list of historical versions of study NCT00617058 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 28, 2012)
  • Percent Change in Insulin Levels [ Time Frame: 24 weeks ]
  • Percent Change in Total Cholesterol [ Time Frame: 24 weeks ]
  • Percent Change in Triglycerides [ Time Frame: 24 weeks ]
  • Incidence of Metabolic Syndrome [ Time Frame: 24 weeks ]
  • Percent Change in Glucose Levels [ Time Frame: 24 weeks ]
  • Percent Change in HDL [ Time Frame: 24 weeks ]
  • Percent Change in LDL [ Time Frame: 24 weeks ]
Original Secondary Outcome Measures  ICMJE
 (submitted: February 14, 2008)
  • change in insulin level [ Time Frame: 26 weeks ]
  • change in cholesterol level [ Time Frame: 26 weeks ]
  • change in triglycerides [ Time Frame: 26 weeks ]
  • Incidence of Metabolic Syndrome [ Time Frame: 26 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Improving Metabolic Parameters of Antipsychotic Child Treatment With Ziprasidone, Aripiprazole, and Clozapine
Official Title  ICMJE Improving Metabolic Parameters of Antipsychotic Child Treatment With Ziprasidone, Aripiprazole, and Clozapine
Brief Summary

The purpose of this study is to evaluate the relative risks and benefits of two approaches to the control of weight gain and other negative side effects in children and adolescents on 2nd generation antipsychotics (SGA):

  • Healthy lifestyle instruction (nutritional and physical activity surveillance and advice) + continuation of current SGA;
  • Add the diabetes drug, metformin + continuation of current SGA.
Detailed Description

The proposed pilot study is being conducted to obtain pilot data to support a grant application for a multi-site randomized controlled trial. The primary objective is to evaluate the relative risks and benefits of two approaches to the control of weight gain and other negative side effects in children and adolescents on 2nd generation antipsychotics (SGA). The critical question being addressed is: What can be done for the many youth who have gained substantial weight or developed high levels of lipids or glucose in their blood on an SGA; but due to their illness require continued treatment with an antipsychotic?

At least 40 youths (and no more than 60) age 10-17 that have gained substantial weight while taking a frequently used SGA: ziprasidone, aripiprazole or clozapine will be randomized to one of two treatments for 6 months:

  • Healthy lifestyle instruction (nutritional and physical activity surveillance and advice) + continuation of current SGA;
  • Add the diabetes drug, metformin + continuation of current SGA.
  • Subjects may also elect to be in an observational arm that involves no intervention but the same major assessments.

Height, weight, body fat, and various blood tests indicative of general health will be collected during the 6 month trial to monitor the health benefits and safety of the interventions.

SGAs are associated with concerning degrees of weight gain and metabolic consequences. Children and adolescents, in whom SGAs are used increasingly for a wide variety of conditions, are particularly vulnerable to these side effects, which adversely affect health and longevity. It is imperative that researchers evaluate the efficacy and safety of interventions designed to prevent and treat the weight gain and metabolic problems caused by antipsychotic treatment of children. Lifestyle interventions and adjunctive medications all hold some promise of efficacy. However, it is essential that these strategies be rigorously evaluated as soon as possible in order to prevent the ongoing health consequences of SGA treatment in another generation of children with serious psychiatric illnesses.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Weight Gain
Intervention  ICMJE
  • Drug: metformin
    open dosed, randomly assigned flexible dose treatment with 250-2000mg/day divided BID or TID
    Other Name: Glucophage
  • Behavioral: healthy lifestyle intervention
    additional component to regular psychiatric visits that includes monitoring of lifestyle and eating behaviors.
Study Arms  ICMJE
  • Experimental: 1
    metformin, 250mg-2000 mg/day, in BID to TID doses for 26 weeks. Open, flexibly adjusted.
    Intervention: Drug: metformin
  • Experimental: 2
    Healthy lifestyle intervention. Additional meeting at each psychiatric visit to review weight changes, level of physical activity and healthy eating behaviors
    Intervention: Behavioral: healthy lifestyle intervention
  • No Intervention: 3
    Self-selected patients will be followed at major timepoints to assess weight and related measures.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: January 7, 2010)
1
Original Estimated Enrollment  ICMJE
 (submitted: February 14, 2008)
60
Actual Study Completion Date  ICMJE September 2010
Actual Primary Completion Date June 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Ages 10 to 17 years (inclusive).
  • Receiving treatment with ziprasidone, aripiprazole or clozapine for the past 56 days or longer.
  • Clinically stable on current treatment regimen (see Rationales below).
  • Stable dose of current psychotropic co-medications for at least 30 days.
  • BMI increase of > 7% within 3 months OR a > 0.5 BMI z-score increase within the past 24 months while taking olanzapine, quetiapine or risperidone, with maintenance of the threshold level of weight gain.
  • Lifetime diagnosis of a schizophrenia spectrum disorder (schizophrenia, schizoaffective disorder, psychotic disorder NOS), a bipolar spectrum disorder (bipolar disorder, bipolar disorder NOS), certain mood disorders (mood disorder NOS, major depressive disorder with psychotic features), or certain disruptive/aggressive disorders (conduct disorder, intermittent explosive disorder, autism spectrum disorder with history of clinically significant levels of disruptive behaviors as defined below) using DSM-IV criteria determined by clinical interview and K-SADS-PL.
  • Sexually active girls must agree to use an effective form of birth control or be abstinent.
  • Principle caretaker is able to participate in study appointments as is clinically indicated.
  • guardian and the child must agree (legally consent and assent) to participation.

Exclusion Criteria:

  • Any medication that would significantly alter glucose, insulin or lipid levels. Prohibited medications will include, but are not limited to: insulin, steroids, topiramate, sibutramine, orlistat, metformin, amantadine, vitamin E (other than in standard multivitamins), antidiabetic drugs, HIV drugs.
  • Major neurological disorder or medical illness that affects weight gain (e.g., unstable thyroid disease), requires a prohibited systemic medication or procedure (e.g., diabetes mellitus [insulin], chronic renal failure [steroids]) or that would prevent participation in physical activity in the healthy lifestyle program.
  • Current active thyroid (TSH >18 microIU/ml), hepatic (2 LFTs >4x upper limits of normal), renal (serum Creatinine >1.4 mg/dL in females and serum Creatinine >1.5 mg/dL in males), cardiac, gastrointestinal, or adrenal disease.
  • Fasting glucose > 125 mg/dL on two occasions indicating need for prompt treatment for diabetes.
  • Child meets DSM-IV criteria for substance abuse or dependence disorder within the past month, not including tobacco abuse or dependence • Current treatment with more than one antipsychotic medication.
  • Current treatment with more than 5 total psychotropic medications (i.e., 4 psychotropics plus SGA).
  • Known hypersensitivity to metformin.
  • Pregnant or breast feeding.
  • Current or lifetime diagnosis of anorexia nervosa or bulimia nervosa.
  • Significant risk for dangerousness to self or to others that makes participating 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 10 Years to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00617058
Other Study ID Numbers  ICMJE 05-3110 GCRC-2529
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Linmarie Sikich, MD, University of North Carolina, Chapel Hill
Study Sponsor  ICMJE University of North Carolina, Chapel Hill
Collaborators  ICMJE Foundation of Hope, North Carolina
Investigators  ICMJE
Principal Investigator: Linmarie Sikich, MD University of North Carolina, Department of Psychiatry
PRS Account University of North Carolina, Chapel Hill
Verification Date November 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP