Acute Impact of Intramuscular (IM) Aripiprazole and Olanzapine on Insulin Resistance in High Risk Prediabetics
Condition: Diabetes
MeSH terms: Insulin Resistance
Study type: Interventional
Phase: Phase 4

Summary: 
      Antipsychotic medicines used to treat mental illnesses have been associated with effects on
      blood sugar control. Laboratory studies have shown that certain medications in particular may
      alter how insulin works. One purpose of this study is determine if antipsychotic medications
      have immediate effects on insulin action in individuals who do not have a mental disorder,
      but who have risk factors for diabetes. A second purpose is to demonstrate the feasibility of
      using volunteers without psychiatric disorders, and who do not take psychiatric medications,
      as a means for studying antipsychotic metabolic effects.
    

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. This
      study will compare the effects of single doses of two antipsychotic medications, olanzapine
      and aripiprazole, on insulin action in nonpsychiatrically ill volunteer subjects.

      Participation in this study will last 6 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 4 more weeks, participants will undergo a 2nd tracer-clamp study, this time receiving
      the antipsychotic not given in the first clamp study. The protocol for this visit is
      otherwise identical to the first clamp study.
    

Intervention name(s): Intramuscular olanzapine, aripiprazole; Intramuscular aripiprazole, olanzapine
Intervention type(s): Drug; Drug
Intervention description(s): 1st clamp: single intramuscular 10.0 mg dose of olanzapine
2nd clamp: single intramuscular 9.75 mg dose of aripiprazole; 1st clamp: single intramuscular 9.75 mg dose of aripiprazole
2nd clamp: single intramuscular 10.0 mg dose of olanzapine
Other intervention name(s): Olanzapine -> Aripiprazole; Aripiprazole -> Olanzapine
Intervention MeSH terms: Olanzapine; Aripiprazole
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Insulin resistance; Antipsychotics; Olanzapine; Aripiprazole