Improving Metabolic Parameters of Antipsychotic Child Treatment With Ziprasidone, Aripiprazole, and Clozapine
Condition: Weight Gain
MeSH terms: Weight Gain
Intervention: metformin; healthy lifestyle intervention
Intervention description: open dosed, randomly assigned flexible dose treatment with 250-2000mg/day divided BID or TID; additional component to regular psychiatric visits that includes monitoring of lifestyle and eating behaviors.
Intervention MeSH terms: Metformin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 10 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: antipsychotic; metformin; children; adolescents

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.
    

Eligibility 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.