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

NCT00512070 | Completed Results DMC

• 1 other identifier: F1D-MC-X302
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

schizophrenia; schizoaffective disorder; bipolar disorder; olanzapine; melatonin; obesity; metabolic syndrome

Outcome Measures

Primary Outcomes (1)

• Nocturnal Melatonin Production

  Nocturnal melatonin production as estimated by assay of urinary 6-sulfatoxymelatonin (aMT6s) adjusted for creatinine

  6 and 12 weeks

Secondary Outcomes (2)

• Weight

  6 weeks & 12 weeks

• Total Cholesterol

  6 weeks & 12 weeks

Study Arms (2)

IIA (0.3mg day melatonin)

EXPERIMENTAL

0.3mg day melatonin

Drug: olanzapine and melatonin

IIB (3.0 mg/day melatonin)

EXPERIMENTAL

3.0 mg/day melatonin

Drug: olanzapine and melatonin

Interventions

olanzapine and melatonin 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.

Also known as: Olanzapine (Zyprexa)

IIA (0.3mg day melatonin); IIB (3.0 mg/day melatonin)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-65;
• DSM-IV-TR diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder;
• Patients who, in the clinical judgment of the investigator, may benefit from a switch to olanzapine;
• 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;
• Willingness and ability to take medications nightly at 10:00 p.m.; and
• The subject or his/her legal representative must provide informed, written consent.

You may not qualify if:

• Females who are pregnant or lactating;
• Concurrent participation or participation within the prior 30 days in any study involving investigational medications;
• Current (within the prior 30 days) diagnosis of substance abuse or dependence;
• Use of olanzapine within the prior three months;
• History of allergy or intolerable side-effects to olanzapine in the past;
• 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;
• Use of fluvoxamine, nifedipine, or warfarin for 30 days prior to Baseline Visit.

Sponsors & Collaborators

• Seattle Institute for Biomedical and Clinical Research: lead
• Eli Lilly and Company: collaborator

Study Sites (1)

VA Puget Sound Health Care System

Tacoma, Washington, 98493, United States

Location

Related Publications (1)

• 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.

  PMID: 16710316 BACKGROUND

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders; Bipolar Disorder; Obesity; Metabolic Syndrome

Interventions

Olanzapine; Melatonin

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Bipolar and Related Disorders; Mood Disorders; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Tryptamines; Indoles; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Limitations and Caveats

Results are limited by small sample size and relatively high percentage of non-completers, which diminishes the power to analyze results. Results of this small sample may not be representative of the larger population and should be interpreted with caution.

Results Point of Contact

• Title: Amanda Wood, PhD
• Organization: VA Puget Sound Health Care System

amanda.wood@va.gov

253-583-1652

Study Officials

• Amanda E Wood, PhD

  VA Puget Sound Health Care System; University of Washington

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2007
• First Posted: August 7, 2007
• Study Start: July 1, 2007
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2024
• Last Updated: January 1, 2025
• Results First Posted: December 5, 2024

Record last verified: 2024-11

Locations

US (1)