Assessment and Comparison of Metabolic Changes in Non-psychotic Adults Taking Iloperidone or Olanzapine or Placebo
Condition: Healthy
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of this pilot randomized clinical trial is to begin to delineate the
      pathophysiological changes associated with antipsychotic associated metabolic side effects.
      The study will be performed in 36 healthy people between the ages of 18 and 30, who have
      never taken an antipsychotic, will undergo baseline laboratory tests before being randomized
      to 5mg BID of olanzapine or 6mg BID of iloperidone or placebo to take for up to 4 weeks. The
      primary outcome measure will be a correlation of early changes in leptin with weight gain. We
      will also record changes in food intake, resting metabolic rate, oral glucose tolerance and
      fasting insulin and glucose levels, lipids and inflammation markers. Subjects will be
      followed closely to monitor for safety throughout the 4-week study and will be discontinued
      if there is a medically significant change in metabolic status or other antipsychotic side
      effects. Metabolic assessments will be performed again at the time of discontinuation or at
      the end of an 4-week period, and change from baseline in the two treatment groups will be
      compared.
    

Detailed description: 
      Study hypotheses:

        1. Early changes (baseline vs day 3) in leptin will correlate with later changes in weight
           (at study termination.)

             1. Olanzapine will cause the greatest increase in calorie consumption from baseline on
                the multi-item meal compared with iloperidone or placebo.

             2. Olanzapine subjects will report the greatest frequency/quantity of eating in food
                diaries, and report increased preference for calorically dense foods (ie, higher
                fat content) compared to iloperidone or placebo.

             3. Early markers of endocrine changes caused by olanzapine will be greater than those
                caused by iloperidone or placebo, and these early changes will correlate with
                weight gain.

        2. Olanzapine will have greater effects on glucose homeostasis than iloperidone or placebo,
           and these effects will be separate from effects on body weight and composition.

             1. Early signs of metabolic disturbance, including glucose intolerance (greater
                excursion on OGTT) and insulin resistance (higher plasma insulin) will precede any
                significant weight gain.

             2. Early evidence of glucose intolerance and/or insulin resistance will predict
                greater metabolic derangements with further dosing of olanzapine, as evidenced by
                exacerbated glucose intolerance on OGTT or higher plasma glucose/insulin levels.
                These effects may not necessarily parallel weight gain.

             3. Olanzapine will be associated with greater markers of inflammation than iloperidone
                or placebo.
    

Intervention name(s): olanzapine; iloperidone; Placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 5mg BID up to 4 weeks; 6 mg BID up to 4 weeks; BID up to 4 weeks
Other intervention name(s): Zyprexa; Fanapt
Intervention MeSH terms: Olanzapine; Iloperidone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment