Melatonin Metabolism Abnormality in Patients With Schizophrenia or Schizoaffective Disorder Treated With Olanzapine
Primary Purpose
Schizophrenia, Schizoaffective Disorder, Bipolar Disorder
Status
Active
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
olanzapine and melatonin
Sponsored by
About this trial
This is an interventional treatment trial for Schizophrenia focused on measuring schizophrenia, schizoaffective disorder, bipolar disorder, olanzapine, melatonin, obesity, metabolic syndrome
Eligibility Criteria
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.
Sites / Locations
- VA Puget Sound Health Care System
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
IIA (0.3mg day melatonin)
IIB (3.0 mg/day melatonin)
Arm Description
0.3mg day melatonin
3.0 mg/day melatonin
Outcomes
Primary Outcome Measures
Nocturnal melatonin production as estimated by assay of urinary 6-sulfatoxymelatonin (aMT6s) adjusted for creatinine
Nocturnal melatonin production as estimated by assay of urinary
Secondary Outcome Measures
Height
height (measured in feet and inches)
Height
height (measured in feet and inches)
Weight
weight (measured in pounds)
Weight
weight (measured in pounds)
Waist measurement
waist measurement (measured in inches)
Waist measurement
waist measurement (measured in inches)
Hip measurement
hip measurement (measured in inches)
Hip measurement
hip measurement (measured in inches)
Metabolic test
metabolic blood panel
Metabolic test
metabolic blood panel
Full Information
NCT ID
NCT00512070
First Posted
August 3, 2007
Last Updated
February 23, 2023
Sponsor
Seattle Institute for Biomedical and Clinical Research
Collaborators
Eli Lilly and Company
1. Study Identification
Unique Protocol Identification Number
NCT00512070
Brief Title
Melatonin Metabolism Abnormality in Patients With Schizophrenia or Schizoaffective Disorder Treated With Olanzapine
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
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 2007 (undefined)
Primary Completion Date
December 2025 (Anticipated)
Study Completion Date
December 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Seattle Institute for Biomedical and Clinical Research
Collaborators
Eli Lilly and Company
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia, Schizoaffective Disorder, Bipolar Disorder, Obesity, Metabolic Syndrome
Keywords
schizophrenia, schizoaffective disorder, bipolar disorder, olanzapine, melatonin, obesity, metabolic syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
IIA (0.3mg day melatonin)
Arm Type
Experimental
Arm Description
0.3mg day melatonin
Arm Title
IIB (3.0 mg/day melatonin)
Arm Type
Experimental
Arm Description
3.0 mg/day melatonin
Intervention Type
Drug
Intervention Name(s)
olanzapine and melatonin
Other Intervention Name(s)
Olanzapine (Zyprexa)
Intervention Description
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.
Primary Outcome Measure Information:
Title
Nocturnal melatonin production as estimated by assay of urinary 6-sulfatoxymelatonin (aMT6s) adjusted for creatinine
Description
Nocturnal melatonin production as estimated by assay of urinary
Time Frame
6 and 12 weeks
Secondary Outcome Measure Information:
Title
Height
Description
height (measured in feet and inches)
Time Frame
6 weeks
Title
Height
Description
height (measured in feet and inches)
Time Frame
12 weeks
Title
Weight
Description
weight (measured in pounds)
Time Frame
6 weeks
Title
Weight
Description
weight (measured in pounds)
Time Frame
12 weeks
Title
Waist measurement
Description
waist measurement (measured in inches)
Time Frame
6 weeks
Title
Waist measurement
Description
waist measurement (measured in inches)
Time Frame
12 weeks
Title
Hip measurement
Description
hip measurement (measured in inches)
Time Frame
6 weeks
Title
Hip measurement
Description
hip measurement (measured in inches)
Time Frame
12 weeks
Title
Metabolic test
Description
metabolic blood panel
Time Frame
6 weeks
Title
Metabolic test
Description
metabolic blood panel
Time Frame
12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amanda E Wood, PhD
Organizational Affiliation
VA Puget Sound Health Care System; University of Washington
Official's Role
Principal Investigator
Facility Information:
Facility Name
VA Puget Sound Health Care System
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98493
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
16710316
Citation
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.
Results Reference
background
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Melatonin Metabolism Abnormality in Patients With Schizophrenia or Schizoaffective Disorder Treated With Olanzapine
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