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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Seattle Institute for Biomedical and Clinical Research
ClinicalTrials.gov Identifier:
NCT00512070
First received: August 3, 2007
Last updated: December 31, 2013
Last verified: December 2013
  Purpose

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 Intervention
Schizophrenia
Schizoaffective Disorder
Bipolar Disorder
Obesity
Metabolic Syndrome
Drug: olanzapine and melatonin

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Seattle Institute for Biomedical and Clinical Research:

Primary Outcome Measures:
  • Nocturnal melatonin production as estimated by assay of urinary 6-sulfatoxymelatonin (aMT6s) adjusted for creatinine [ Time Frame: 6 and 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Metabolic indices including weight, waist and hip measurements, and metabolic tests [ Time Frame: 6 and 12 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: July 2007
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IIA
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 Name: Olanzapine (Zyprexa)
Experimental: IIB
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 Name: Olanzapine (Zyprexa)

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00512070

Locations
United States, Washington
VA Puget Sound Health Care System
Tacoma and Seattle, Washington, United States, 98493
Sponsors and Collaborators
Seattle Institute for Biomedical and Clinical Research
Eli Lilly and Company
Investigators
Principal Investigator: Nael Kilzieh, M.D. VA Puget Sound Health Care System, Seattle and Tacoma, WA; University of Washington, Dept. of Psychiatry and Behavioral Sciences
  More Information

Publications:
Responsible Party: Seattle Institute for Biomedical and Clinical Research
ClinicalTrials.gov Identifier: NCT00512070     History of Changes
Other Study ID Numbers: F1D-MC-X302
Study First Received: August 3, 2007
Last Updated: December 31, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Seattle Institute for Biomedical and Clinical Research:
schizophrenia
schizoaffective disorder
bipolar disorder
olanzapine
melatonin
obesity
metabolic syndrome

Additional relevant MeSH terms:
Bipolar Disorder
Congenital Abnormalities
Disease
Metabolic Syndrome X
Obesity
Psychotic Disorders
Schizophrenia
Syndrome
Affective Disorders, Psychotic
Body Weight
Glucose Metabolism Disorders
Hyperinsulinism
Insulin Resistance
Mental Disorders
Metabolic Diseases
Mood Disorders
Nutrition Disorders
Overnutrition
Overweight
Pathologic Processes
Schizophrenia and Disorders with Psychotic Features
Signs and Symptoms
Melatonin
Olanzapine
Antiemetics
Antioxidants
Antipsychotic Agents
Autonomic Agents
Central Nervous System Agents
Central Nervous System Depressants

ClinicalTrials.gov processed this record on November 23, 2014