Examining the Effects of Antipsychotic Medications on Insulin Sensitivity
Condition: Diabetes
MeSH terms: Insulin Resistance
Study type: Interventional
Phase: Phase 4

Summary: 
      This study will examine the effects of two different antipsychotic medications on control of
      blood sugar in people who are at risk of diabetes but mentally healthy.
    

Detailed description: 
      Antipsychotic medications are those that treat the most severe psychiatric symptoms, such as
      hallucinations, paranoid thoughts, and delusions. Research shows that some of these
      medications may put people at a higher risk of metabolic derangements, such as insulin
      resistance. Certain antipsychotics, like clozapine and olanzapine, are associated with a
      higher risk of metabolic side effects than others, like aripiprazole and ziprasidone. Because
      people with schizophrenia may experience adverse side effects from switching antipsychotic
      medications and because it is difficult to find people with schizophrenia who do not have
      experience taking antipsychotics, this study will use people without psychiatric disorders
      who are at risk for diabetes in place of people with schizophrenia. The study will compare
      the effects of single doses of two antipsychotic medications, olanzapine and aripiprazole, on
      insulin action in this population. In addition to determining metabolic effects of these
      medications, this study will also seek to demonstrate the feasibility of using mentally
      healthy people at risk of diabetes as a substitute for people with schizophrenia in studying
      these effects.

      Participation in this study will last 4 weeks. Participants will first complete a screening
      visit that will include the following: an oral glucose tolerance test (OGTT), which involves
      a blood draw, consumption of a sugar drink, and then a second blood draw; a review of medical
      and psychiatric history, including use of medicines and psychiatric medications; and
      measurement of participants' height and weight. The second visit, scheduled 2 weeks after
      screening, will include a tracer-clamp study to test how participants' bodies handle sugar.
      The tracer-clamp study will be conducted over the course of one night and morning and will
      require participants to stay at the study location overnight. At 3 AM, participants will
      receive an intravenous line (IV) with a sugar solution. Just before 8 AM, they will receive a
      second IV in the opposite arm that will draw blood and monitor blood sugar levels.

      At 8 AM, participants will begin receiving insulin in the first IV; blood samples will be
      drawn and blood sugar levels will be monitored during this time to ensure they remain within
      a healthy range. At 11 AM, participants will receive an injection of an antipsychotic
      medication into their arm muscles. The antipsychotic, which will be randomly assigned, will
      be either olanzapine or aripiprazole. Participants will be monitored for 3 hours after
      receiving the injection of antipsychotic medication; during this time, more blood samples
      will be drawn, blood sugar levels will be monitored to ensure they are within a healthy
      range, and secondary medications will be available to counteract certain side effects of the
      antipsychotics. After 2 more weeks, participants will undergo a third study visit in which
      they repeat the OGTT.
    

Intervention name(s): Olanzapine; Aripiprazole
Intervention type(s): Drug; Drug
Intervention description(s): Single intramuscular 10-mg dose; Single intramuscular 9.75-mg dose
Other intervention name(s): Zyprexa; Abilify
Intervention MeSH terms: Olanzapine; Aripiprazole
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Insulin Resistance; Antipsychotic Medications