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

February 23, 2023 updated by: Seattle Institute for Biomedical and Clinical Research

Melatonin Metabolism Abnormality in Patients With Schizophrenia or Schizoaffective Disorder Treated With Olanzapine and Melatonin Dose Finding for the Correction of the Metabolic Abnormality

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

20

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Washington
      • Tacoma, Washington, United States, 98493
        • VA Puget Sound Health Care System

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Nocturnal melatonin production as estimated by assay of urinary 6-sulfatoxymelatonin (aMT6s) adjusted for creatinine
Time Frame: 6 and 12 weeks
Nocturnal melatonin production as estimated by assay of urinary
6 and 12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Height
Time Frame: 6 weeks
height (measured in feet and inches)
6 weeks
Height
Time Frame: 12 weeks
height (measured in feet and inches)
12 weeks
Weight
Time Frame: 6 weeks
weight (measured in pounds)
6 weeks
Weight
Time Frame: 12 weeks
weight (measured in pounds)
12 weeks
Waist measurement
Time Frame: 6 weeks
waist measurement (measured in inches)
6 weeks
Waist measurement
Time Frame: 12 weeks
waist measurement (measured in inches)
12 weeks
Hip measurement
Time Frame: 6 weeks
hip measurement (measured in inches)
6 weeks
Hip measurement
Time Frame: 12 weeks
hip measurement (measured in inches)
12 weeks
Metabolic test
Time Frame: 6 weeks
metabolic blood panel
6 weeks
Metabolic test
Time Frame: 12 weeks
metabolic blood panel
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Seattle Institute for Biomedical and Clinical Research

Collaborators

Eli Lilly and Company

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2007

Primary Completion (Anticipated)

December 1, 2025

Study Completion (Anticipated)

December 1, 2025

Study Registration Dates

First Submitted

August 3, 2007

First Submitted That Met QC Criteria

August 6, 2007

First Posted (Estimate)

August 7, 2007

Study Record Updates

Last Update Posted (Estimate)

February 27, 2023

Last Update Submitted That Met QC Criteria

February 23, 2023

Last Verified

February 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • F1D-MC-X302

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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