Melatonin Metabolism Abnormality in Patients With Schizophrenia or Schizoaffective Disorder Treated With Olanzapine
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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 |
- 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 ]
- 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 |
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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;
- 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;
- Use of fluvoxamine, nifedipine, or warfarin for 30 days prior to Baseline Visit.
Contacts and Locations| Contact: Amanda E Wood, PhD | (253) 583-1652 | amanda.wood@va.gov |
| United States, Washington | |
| VA Puget Sound Health Care System | Recruiting |
| Tacoma and Seattle, Washington, United States, 98493 | |
| 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 18, 2012 |
| 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:
|
Congenital Abnormalities Bipolar Disorder Obesity Psychotic Disorders Schizophrenia Metabolic Syndrome X Affective Disorders, Psychotic Mood Disorders Mental Disorders Overnutrition Nutrition Disorders Overweight Body Weight Signs and Symptoms Schizophrenia and Disorders with Psychotic Features |
Insulin Resistance Hyperinsulinism Glucose Metabolism Disorders Metabolic Diseases Melatonin Olanzapine Central Nervous System Depressants Physiological Effects of Drugs Pharmacologic Actions Central Nervous System Agents Therapeutic Uses Antioxidants Molecular Mechanisms of Pharmacological Action Protective Agents Antipsychotic Agents |
ClinicalTrials.gov processed this record on May 22, 2013