An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
Condition: Schizophrenia; Schizoaffective Disorder; Schizophreniform Disorder; Bipolar Disorder; Autism Spectrum Disorders
MeSH terms: Schizophrenia; Bipolar Disorder; Autism Spectrum Disorder; Psychotic Disorders
Study type: Interventional
Phase: Phase 4

Summary: 
      The aim of this study is to evaluate the effectiveness, safety, and tolerability of metformin
      treatment in children and adolescents suffering from weight gain secondary to use of atypical
      antipsychotic medications. In this 12 week, open-label study we will investigate metformin's
      effects on weight control and/or weight loss. We hypothesize that metformin would prevent
      further weight gain or lead to weight loss, resulting in amelioration of one of the most
      significant side effects of atypical antipsychotic use.
    

Detailed description: 
      Patients taking olanzapine, risperidone, or quetiapine with increased BMI of at least 10%
      over the previous 2 months of atypical therapy will be eligible for the study. Subjects will
      need to have been on a stable dose of their antipsychotic medications at the time of
      enrollment (stable x2 weeks) and will remain on the same atypical dose, if possible,
      throughout the study. The dosing of metformin will start at 500mg per day and increase up to
      a maximum dose of 1500mg daily. Determination of weight gain during the course of the study
      will be based on the subject's weight at enrollment and subsequent visits. The patients will
      be asked not to vary their dietary or physical activity habits during the study.

      Interpretation of Data: The study's primary outcome measure will be change in weight and body
      mass index at 12 weeks of metformin treatment. Additionally, skin-fold test and abdominal
      girth will be measured at baseline and endpoint.

      Risks: Generally, metformin is well-tolerated. However, there may be unknown risks associated
      with exposure to a new medication in a clinical population where this specific compound has
      not been studied extensively. The general and rare side effects are listed below. These risks
      will be minimized by careful monitoring and higher than standard of care safety evaluations.
      In addition, an individual's symptoms could potentially remain unchanged or worsen by
      initiating this medication, or from delaying initiation of a potentially more effective
      alternative treatment. For these reasons, participation in the study is entirely voluntary
      and consent may be withdrawn at any time without any repercussions and will result in the
      patient being immediately discontinued from the study. If at any time the clinician believes
      that the patient is not benefiting from the study, the study will be discontinued and
      endpoint measures will be obtained if possible. A risk-benefit analysis, weighing clinical
      improvement against side effects will be done at each visit and will determine further
      inclusion in the study.

      Subjects and their guardians will be asked repeatedly to inform study staff of any side
      effects. Subjects are informed of the potential side effects and the importance of alerting
      study staff to the side effects in the consent and assent forms. Side effect data will be
      collected at baseline and every other week, but subjects are encouraged to give relevant
      information at every clinical evaluation.

      Alternative treatments include no treatment with an attendant risk of increased weight gain,
      potentially leading to health hazard. Other medications that are available are not
      extensively used and widely accepted. These other medication options will be discussed as
      alternatives during the consent process. Also, life-style modifications including healthy
      diet habits and increased physical activity will be discussed during the consent process as
      well.
    

Intervention name(s): Metformin
Intervention type(s): Drug
Intervention description(s): open-label, flexible dosing
Other intervention name(s): Glucophage
Intervention MeSH terms: Metformin
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: weight gain; obesity; metabolism