Examining Risk Factors for Atypical Antipsychotic Metabolic Side Effects
Condition: Schizophrenia
MeSH terms: Schizophrenia
Study type: Interventional

Summary: 
      This study will examine possible causes of metabolic side effects in people taking atypical
      antipsychotic (AAP) medications.
    

Detailed description: 
      Antipsychotic medications are used to treat some of the most severe symptoms of mental
      illness, such as hallucinations and irrational outbursts. Atypical antipsychotics (AAPs) are
      a group of newer, second generation antipsychotic medications that effectively treat
      psychotic symptoms but that also have severe side effects. One side effect is an increased
      risk of metabolic syndrome, which is a cluster of conditions that together increase the risk
      of heart disease, stroke, type 2 diabetes, and endothelial dysfunction-dysfunction of the
      cells that line the inner surface of blood cells. Schizophrenic patients taking atypical
      antipsychotics are more than twice as likely as the general population to experience
      metabolic syndrome. Certain genetic variants associated with folate metabolism, as well as
      low dietary folate, may lead to the development of metabolic syndrome and its associated
      diseases. These factors have been studied in the general population, but not in a group of
      schizophrenic patients taking antipsychotics. This study will examine the relationship among
      folic acid, variants in the gene methylenetetrahydrofolate reductase, and metabolic syndrome
      and its associated diseases in people with schizophrenia who are taking atypical
      antipsychotics. The study will also evaluate the use of folic acid supplementation for
      treating metabolic syndrome in this population.

      Participation in this study will involve two phases. The first phase will involve
      recruitment, screening, and testing of participants taking antipsychotics and will last 4
      years. During this phase, participants will attend one study visit in which they will undergo
      a screening for metabolic syndrome and have the following measured: endothelial functioning,
      body size, diet, physical activity, medication history, and genetic makeup. Participants who
      have metabolic syndrome will be invited to participate in Phase 2.

      Phase 2 will run concurrently with Phase 1, but will extend to 5 years, in order to give all
      participants an opportunity to continue from one phase to the next if they meet entry
      criteria. Participants in Phase 2 will attend four study visits over the course of 3 months:
      one at the beginning of the phase and one after each month of the study. After the first
      study visit, participants will be given folic acid to take daily for the 3 months. At each
      study visit, participants will be asked about thoughts, illness, functioning, diet,
      medication side effects, recent medication history, smoking history, alcohol intake, and
      exercise habits. On the first and last visits, participants will undergo additional tests of
      genetics, blood hormone levels, and blood vessel functioning, and additional measurements
      will be made of height, weight, vital signs, and body size. The Phase 2 study is now
      inactive.

      Phase 2B is active and currently recruiting participants. This is a randomized, placebo
      controlled study of folate supplementation. Participants in phase 2B will attend 6 study
      visits over the course of 6 months. At the first study visit they will be randomized to
      either folic acid 5mg daily for 4 months or placebo. This 4 month period is followed by a 2
      month follow up visit, when no supplementation is given. At each study visit, participants
      will be asked about thoughts, illness, functioning, diet, medication side effects, recent
      medication history, smoking history, alcohol intake, and exercise habits. On the first and
      last visits, participants will undergo additional tests of genetics, blood hormone levels,
      and blood vessel functioning, and additional measurements will be made of height, weight,
      vital signs, and body size.
    

Intervention name(s): Folic Acid; Placebo
Intervention type(s): Dietary Supplement; Other
Intervention description(s): 5 mg of folic acid taken daily for 3 months in an open label fashion; Subjects may receive placebo (a sugar pill) for 4 months
Other intervention name(s): Folate
Intervention MeSH terms: Folic Acid
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Other
Keywords: Antipsychotic; Metabolic Syndrome; Insulin Resistance; Endothelial Function