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”

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 or schizoaffective disorder.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Dose Comparison, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: August 2009

To investigate the relationship between olanzapine, melatonin, and metabolic functioning, this pilot study is evaluating 20 stable patients with schizophrenia or schizoaffective 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.

Intervention(s) in this Clinical Trial

• 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 ration 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.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: IIA
• Experimental: IIB

Primary Measures

• Nocturnal melatonin production as estimated by assay of urinary 6-sulfatoxymelatonin (aMT6s) adjusted for creatinine
  • Time Frame: 6 and 12 weeks
    Safety Issue?: No

Secondary Measures

• Metabolic indices including weight, waist and hip measurements, and metabolic tests
  • Time Frame: 6 and 12 weeks
    Safety Issue?: No

Inclusion Criteria:

• 1. Age 18-65;
• 2. DSM-IV-TR diagnosis of schizophrenia or schizoaffective disorder;
• 3. Psychiatrically stable as evidenced by no psychiatric hospitalizations and no changes in psychiatric medications within the prior three months, and as confirmed by clinical interview during the screening phase (Clinical Global Impression Scale, Severity score rating < 5). (Minor changes, such as dose adjustment or PRN medications, in psychiatric medications may be allowed as per the discretion of the study doctor.);
• 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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Seattle Institute for Biomedical and Clinical Research

Overall Clinical Trial Officials and Contacts

Andre Tapp, M.D. Principal Investigator VA Puget Sound Health Care System, Seattle and Tacoma, WA; University of Washington, Dept. of Psychiatry and Behavioral Sciences  

Overall Contact: Annette Kennedy, Psy.D. (253) 583-1614 Annette.Kennedy@va.gov

Information obtained from ClinicalTrials.gov on November 20, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00512070

Study ID Number: F1D-MC-X302

ClinicalTrials.gov Identifier: NCT00512070

Health Authority: United States: Institutional Review Board