Assessment and Comparison of Metabolic Changes in Non-psychotic Adults Taking Iloperidone or Olanzapine or Placebo
Condition: Healthy
Intervention: olanzapine; iloperidone; Placebo
Intervention description: 5mg BID up to 4 weeks; 6 mg BID up to 4 weeks; BID up to 4 weeks
Intervention MeSH terms: Olanzapine; Iloperidone
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 31.0
Sex: All
Minimum age: 18 Years
Maximum age: 35 Years
Healthy volunteers: Accepts Healthy Volunteers

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female between the ages of 18-35 with no history of any Axis-I diagnosis

          -  Does not meet criteria for substance abuse or dependence in the past six months

          -  Female subjects will use barrier-method, non-hormonal contraception

          -  Capacity to understand all the relevant risks and potential benefits of the study
             (informed consent)

          -  Must be able to speak and read English

        Exclusion Criteria:

          -  Current or past Axis I psychiatric diagnosis, including alcohol or substance abuse or
             dependence (except nicotine or caffeine), but not including minor Axis I disorders
             (e.g. simple phobia)

          -  Lifetime use of psychotropic medications, including antipsychotics, antidepressants,
             mood stabilizers, and anxiolytics

          -  Presence or history of medical or neurological illness that, in the judgment of the
             investigator, could influence the results of the study

          -  Diagnosis of diabetes, hemoglobin A1C > 6.5, hypertension, or dyslipidemias, or
             elevated random or fasting glucose, abnormal lipid levels, BP 130/85

          -  BMI 25 or < 19, history of BMI >35, and/or waist circumference >35 inches for females,
             40 inches for males

          -  Subjects who are pregnant or breast-feeding or planning to become pregnant during the
             study

          -  Acute suicidality

          -  Meets criteria for a Diagnostic and Statistical Manual, Version 4 (DSM-IV) defined
             eating disorder

          -  Use of, or clinical indication for, one or more of the following medications: lithium,
             anti-epileptic medication, steroids (oral or inhaled), stimulants, serotonin reuptake
             inhibitors, mirtazapine, tricyclic antidepressants, thyroid supplementation,
             sibutramine, metformin, thiazolidinediones, beta-blockers, clonidine, niacin

          -  Subjects who have had >10% change in their body weight within the three months prior
             to enrollment

          -  HIV positive subjects

          -  Presence of mental retardation or pervasive developmental disorder

          -  History of recent (within 6 months) significant self-injurious behavior or violence

          -  Daily multivitamin or B-complex vitamin use

          -  A known history of dieting and difficulty with weight loss

          -  A strong family history of diabetes and/or heart disease

          -  History of congenital long QT syndrome or prolonged corrected QT interval (QTc) on
             screening EKG (>450ms)

          -  Concomitant use of any medication that inhibits 2D6 or 3A4 metabolism

          -  Low serum potassium or magnesium