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Assessment and Comparison of Metabolic Changes in Non-psychotic Adults Taking Iloperidone or Olanzapine or Placebo

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ClinicalTrials.gov Identifier: NCT01920802
Recruitment Status : Completed
First Posted : August 12, 2013
Results First Posted : March 20, 2017
Last Update Posted : March 20, 2017
Sponsor:
Collaborator:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
New York State Psychiatric Institute

Brief 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.

Condition or disease Intervention/treatment Phase
Healthy Drug: olanzapine Drug: iloperidone Drug: Placebo Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 31 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Quantitative Assessment and Comparison of Metabolic Changes in Non-psychotic Adults Taking the Antipsychotic Medications Fanapt (Iloperidone) or Zyprexa (Olanzapine) or Placebo
Study Start Date : November 2012
Actual Primary Completion Date : August 2014
Actual Study Completion Date : September 2014

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: olanzapine
5mg BID olanzapine for up to 4 weeks
Drug: olanzapine
5mg BID up to 4 weeks
Other Name: Zyprexa

Experimental: iloperidone
6mg BID iloperidone up to 4 weeks
Drug: iloperidone
6 mg BID up to 4 weeks
Other Name: Fanapt

Placebo Comparator: placebo
BID placebo up to 4 weeks
Drug: Placebo
BID up to 4 weeks




Primary Outcome Measures :
  1. Change in Body Weight [ Time Frame: baseline and 6 week visit ]
    Delineate a pathophysiological mechanism of antipsychotic induced weight gain

  2. Change in Adiposity [ Time Frame: Baseline to Day 28 ]
    Total fat mass (excluding head) from baseline to Day 28


Secondary Outcome Measures :
  1. Change in Leptin [ Time Frame: change in baseline to Day 3 ]
    Leptin levels measured at Day 3 compared to baseline


Other Outcome Measures:
  1. Change Glucose in People Taking Olanzapine or Iloperidone [ Time Frame: Baseline to study termination (about 12 weeks) ]
    To quantify, prospectively, change in glucose from baseline to Day 28

  2. Change in Insulin [ Time Frame: Baseline to Day 28 ]
    Change in Insulin levels from baseline to Day 28

  3. Insulin Resistance [ Time Frame: Baseline to Day 28 ]
    Homeostatic model assessment for Insulin Resistance (HOMA-IR) is a method for assessing β-cell function and insulin resistance (IR) from basal (fasting) glucose and insulin.

  4. Change in Food Intake [ Time Frame: Baseline to Day 28 ]
    Total grams of food consumed

  5. Change in Lipid Metabolism [ Time Frame: Baseline to Day 28 ]
    Change in lipid metabolism as measured by cholesterol/HDL ratio



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 35 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01920802


Locations
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United States, New York
New York State Psychiatric Institute
New York, New York, United States, 10032
Sponsors and Collaborators
New York State Psychiatric Institute
Novartis Pharmaceuticals
Investigators
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Principal Investigator: Jeffrey Lieberman, MD New York State Psychiatric Institute

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Responsible Party: New York State Psychiatric Institute
ClinicalTrials.gov Identifier: NCT01920802     History of Changes
Other Study ID Numbers: 6525
First Posted: August 12, 2013    Key Record Dates
Results First Posted: March 20, 2017
Last Update Posted: March 20, 2017
Last Verified: January 2017

Additional relevant MeSH terms:
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Olanzapine
Iloperidone
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents