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

NCT ID: NCT00512070

Last Updated: 2025-01-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-07-31
• Study Completion Date: 2024-12-31

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.

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.

Conditions

Schizophrenia; Schizoaffective Disorder; Bipolar Disorder; Obesity; Metabolic Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

IIA (0.3mg day melatonin)

0.3mg day melatonin

Group Type: EXPERIMENTAL

olanzapine and melatonin

Intervention Type: DRUG

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.

IIB (3.0 mg/day melatonin)

3.0 mg/day melatonin

Group Type: EXPERIMENTAL

olanzapine and melatonin

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Olanzapine (Zyprexa)

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Seattle Institute for Biomedical and Clinical Research

OTHER

Sponsor Role: lead

Eli Lilly and Company

INDUSTRY

Sponsor Role: collaborator

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Amanda E Wood, PhD

Role: PRINCIPAL_INVESTIGATOR

VA Puget Sound Health Care System; University of Washington

Locations

VA Puget Sound Health Care System

Tacoma, Washington, United States

Countries

United States

References

Raskind MA, Burke BL, Crites NJ, Tapp AM, Rasmussen DD. Olanzapine-induced weight gain and increased visceral adiposity is blocked by melatonin replacement therapy in rats. Neuropsychopharmacology. 2007 Feb;32(2):284-8. doi: 10.1038/sj.npp.1301093. Epub 2006 May 10.

Reference Type: BACKGROUND

PMID: 16710316 (View on PubMed)

Other Identifiers

F1D-MC-X302

Identifier Type: -

Identifier Source: org_study_id