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

This study has been terminated.
(Terminated in lieu of similar,competing large, multi-site study.)
Sponsor:
Collaborator:
Foundation of Hope, North Carolina
Information provided by (Responsible Party):
Linmarie Sikich, MD, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT00617058
First received: February 5, 2008
Last updated: November 28, 2012
Last verified: November 2012
  Purpose

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.

Condition Intervention Phase
Weight Gain
Drug: metformin
Behavioral: healthy lifestyle intervention
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Improving Metabolic Parameters of Antipsychotic Child Treatment With Ziprasidone, Aripiprazole, and Clozapine

Resource links provided by NLM:


Further study details as provided by University of North Carolina, Chapel Hill:

Primary Outcome Measures:
  • Percent Change in BMI [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  • Absolute Change in Weight [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  • Percent Change in Fat Mass [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  • Percent Change in Weight [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Percent Change in Insulin Levels [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  • Percent Change in Total Cholesterol [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  • Percent Change in Triglycerides [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  • Incidence of Metabolic Syndrome [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  • Percent Change in Glucose Levels [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  • Percent Change in HDL [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  • Percent Change in LDL [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 1
Study Start Date: March 2007
Study Completion Date: September 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
metformin, 250mg-2000 mg/day, in BID to TID doses for 26 weeks. Open, flexibly adjusted.
Drug: metformin
open dosed, randomly assigned flexible dose treatment with 250-2000mg/day divided BID or TID
Other Name: Glucophage
Experimental: 2
Healthy lifestyle intervention. Additional meeting at each psychiatric visit to review weight changes, level of physical activity and healthy eating behaviors
Behavioral: healthy lifestyle intervention
additional component to regular psychiatric visits that includes monitoring of lifestyle and eating behaviors.
No Intervention: 3
Self-selected patients will be followed at major timepoints to assess weight and related measures.

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.

  Eligibility

Ages Eligible for Study:   10 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT00617058

Locations
United States, North Carolina
University of North Carolina, Department of Psychiatry
Chapel HIll, North Carolina, United States, 27599
Sponsors and Collaborators
University of North Carolina, Chapel Hill
Foundation of Hope, North Carolina
Investigators
Principal Investigator: Linmarie Sikich, MD University of North Carolina, Department of Psychiatry
  More Information

No publications provided

Responsible Party: Linmarie Sikich, MD, Associate Professor of Psychiatry, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT00617058     History of Changes
Other Study ID Numbers: 05-3110 GCRC-2529
Study First Received: February 5, 2008
Results First Received: October 29, 2012
Last Updated: November 28, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by University of North Carolina, Chapel Hill:
antipsychotic
metformin
children
adolescents

Additional relevant MeSH terms:
Weight Gain
Body Weight Changes
Body Weight
Signs and Symptoms
Metformin
Aripiprazole
Antipsychotic Agents
Ziprasidone
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Tranquilizing Agents
Central Nervous System Depressants
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Dopamine Antagonists
Dopamine Agents

ClinicalTrials.gov processed this record on September 18, 2014