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

NCT00617058 | Terminated Phase 2 Results DMC

• 1 other identifier: 05-3110 GCRC-2529
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

Weight Gain

Keywords

antipsychotic; metformin; children; adolescents

Outcome Measures

Primary Outcomes (4)

• Percent Change in BMI

  24 weeks

• Absolute Change in Weight

  24 weeks

• Percent Change in Fat Mass

  24 weeks

• Percent Change in Weight

  24 weeks

Secondary Outcomes (7)

• Percent Change in Insulin Levels

  24 weeks

• Percent Change in Total Cholesterol

  24 weeks

• Percent Change in Triglycerides

  24 weeks

• Incidence of Metabolic Syndrome

  24 weeks

• Percent Change in Glucose Levels

  24 weeks

Study Arms (3)

1

EXPERIMENTAL

metformin, 250mg-2000 mg/day, in BID to TID doses for 26 weeks. Open, flexibly adjusted.

Drug: metformin

2

EXPERIMENTAL

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

3

NO INTERVENTION

Self-selected patients will be followed at major timepoints to assess weight and related measures.

Interventions

metformin DRUG

open dosed, randomly assigned flexible dose treatment with 250-2000mg/day divided BID or TID

Also known as: Glucophage

1

healthy lifestyle intervention BEHAVIORAL

additional component to regular psychiatric visits that includes monitoring of lifestyle and eating behaviors.

2

Eligibility Criteria

• Age: 10 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• Foundation of Hope, North Carolina: collaborator

Study Sites (1)

University of North Carolina, Department of Psychiatry

Chapel Hill, North Carolina, 27599, United States

Location

MeSH Terms

Conditions

Weight Gain

Interventions

Metformin

Condition Hierarchy (Ancestors)

Body Weight Changes; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Limitations and Caveats

In terms of study limitations, this research study was only able to enroll a single study participant before the trial was terminated prematurely due to study start-up for a larger, multisite effort examining similar outcome measures.

Results Point of Contact

• Title: Linmarie Sikich, M.D.
• Organization: The University of North Carolina at Chapel Hill

lsikich@med.unc.edu

(919) 972-7499

Study Officials

• Linmarie Sikich, MD

  University of North Carolina, Department of Psychiatry

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Psychiatry

Study Record Dates

• First Submitted: February 5, 2008
• First Posted: February 15, 2008
• Study Start: March 1, 2007
• Primary Completion: June 1, 2010
• Study Completion: September 1, 2010
• Last Updated: December 31, 2012
• Results First Posted: December 31, 2012

Record last verified: 2012-11

Locations

US (1)