Melatonin Metabolism Abnormality in Patients With Schizophrenia or Schizoaffective Disorder Treated With Olanzapine

Sponsor
Seattle Institute for Biomedical and Clinical Research (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT00512070
Collaborator
Eli Lilly and Company (Industry)
20
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Study Details

Study Description

Brief Summary

Atypical antipsychotic medications, such as olanzapine, cause metabolic side effects, including weight gain, extra fat around the middle of the body, high blood sugar, and high cholesterol. One of the mechanisms by which these medications may cause these effects is by reducing plasma melatonin. This study is a pilot project to evaluate 1) the effect of olanzapine on melatonin secretion levels and 2) the effect of melatonin on olanzapine-induced changes in melatonin secretion in patients with schizophrenia, schizoaffective, or bipolar disorder.

Condition or Disease Intervention/Treatment Phase
  • Drug: olanzapine and melatonin
N/A

Detailed Description

To investigate the relationship between olanzapine, melatonin, and metabolic functioning, this pilot study is evaluating 20 patients with schizophrenia, schizoaffective disorder, or bipolar disorder over 15 weeks under three experimental conditions: 1) baseline (two weeks treatment with already established antipsychotic medication other than olanzapine or clozapine), 2) six weeks treatment with olanzapine only, and 3) six weeks treatment with olanzapine and melatonin. Half of the patients will receive 0.3 mg of oral melatonin and half will receive 3.0 mg of melatonin. Nocturnal melatonin production, as estimated by assay of urinary 6-sulfatoxymelatonin(aMT6s) adjusted for creatinine, will be measured weekly. In addition, weekly measurements of weight and other metabolic indices, including waist and hip measurements, fasting glucose, serum insulin, cholesterol, triglycerides, and leptin will be taken. It is anticipated that there will be an olanzapine-induced decrease in melatonin production. Furthermore, it is expected that the decrease in melatonin production associated with olanzapine treatment will be reversed by administration of melatonin with olanzapine.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
20 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Melatonin Metabolism Abnormality in Patients With Schizophrenia or Schizoaffective Disorder Treated With Olanzapine and Melatonin Dose Finding for the Correction of the Metabolic Abnormality
Study Start Date :
Jul 1, 2007
Anticipated Primary Completion Date :
Dec 1, 2022
Anticipated Study Completion Date :
Dec 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: IIA (0.3mg day melatonin)

0.3mg day melatonin

Drug: olanzapine and melatonin
In treatment phase I, all subjects will receive olanzapine, 10-25 mg/day. In treatment phase II, all subjects will receive olanzapine (10-25 mg/day) plus melatonin. Subjects will be randomized at a ratio of 1:1 to receive melatonin, 0.3 mg/day or 3.0 mg/day. Group IIA will receive 0.3mg day melatonin. Group IIB will receive 3.0 mg/day melatonin.
Other Names:
  • Olanzapine (Zyprexa)
  • Experimental: IIB (3.0 mg/day melatonin)

    3.0 mg/day melatonin

    Drug: olanzapine and melatonin
    In treatment phase I, all subjects will receive olanzapine, 10-25 mg/day. In treatment phase II, all subjects will receive olanzapine (10-25 mg/day) plus melatonin. Subjects will be randomized at a ratio of 1:1 to receive melatonin, 0.3 mg/day or 3.0 mg/day. Group IIA will receive 0.3mg day melatonin. Group IIB will receive 3.0 mg/day melatonin.
    Other Names:
  • Olanzapine (Zyprexa)
  • Outcome Measures

    Primary Outcome Measures

    1. Nocturnal melatonin production as estimated by assay of urinary 6-sulfatoxymelatonin (aMT6s) adjusted for creatinine [6 and 12 weeks]

      Nocturnal melatonin production as estimated by assay of urinary

    Secondary Outcome Measures

    1. Height [6 weeks]

      height (measured in feet and inches)

    2. Height [12 weeks]

      height (measured in feet and inches)

    3. Weight [6 weeks]

      weight (measured in pounds)

    4. Weight [12 weeks]

      weight (measured in pounds)

    5. Waist measurement [6 weeks]

      waist measurement (measured in inches)

    6. Waist measurement [12 weeks]

      waist measurement (measured in inches)

    7. Hip measurement [6 weeks]

      hip measurement (measured in inches)

    8. Hip measurement [12 weeks]

      hip measurement (measured in inches)

    9. Metabolic test [6 weeks]

      metabolic blood panel

    10. Metabolic test [12 weeks]

      metabolic blood panel

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Age 18-65;

    2. DSM-IV-TR diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder;

    3. Patients who, in the clinical judgment of the investigator, may benefit from a switch to olanzapine;

    4. Females must be of non-child bearing potential (i.e., surgically sterilized, or at least one year post-menopausal) or on an appropriate dose of oral/depot contraceptives or using barrier protection and not breast-feeding. Females must have a urine pregnancy test at screening;

    5. Willingness and ability to take medications nightly at 10:00 p.m.; and

    6. The subject or his/her legal representative must provide informed, written consent.

    Exclusion Criteria:
    1. Females who are pregnant or lactating;

    2. Concurrent participation or participation within the prior 30 days in any study involving investigational medications;

    3. Current (within the prior 30 days) diagnosis of substance abuse or dependence;

    4. Use of olanzapine within the prior three months;

    5. History of allergy or intolerable side-effects to olanzapine in the past;

    6. History of significant head trauma, defined as head trauma resulting in loss of consciousness for more than five minutes and/or neurological or cognitive sequelae;

    7. Evidence of any clinically relevant disease (e.g., renal or hepatic impairment, significant coronary artery disease, cerebrovascular disease, or cancer) or any clinical finding that in the opinion of the investigator could potentially be negatively affected by study participation or that could potentially affect study participation is criterion for exclusion from the study;

    8. Use of fluvoxamine, nifedipine, or warfarin for 30 days prior to Baseline Visit.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 VA Puget Sound Health Care System Tacoma Washington United States 98493

    Sponsors and Collaborators

    • Seattle Institute for Biomedical and Clinical Research
    • Eli Lilly and Company

    Investigators

    • Principal Investigator: Amanda E Wood, PhD, VA Puget Sound Health Care System; University of Washington

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Seattle Institute for Biomedical and Clinical Research
    ClinicalTrials.gov Identifier:
    NCT00512070
    Other Study ID Numbers:
    • F1D-MC-X302
    First Posted:
    Aug 7, 2007
    Last Update Posted:
    Jul 9, 2020
    Last Verified:
    Jul 1, 2020

    Study Results

    No Results Posted as of Jul 9, 2020