SchizophreniaNCT00512070
Melatonin Metabolism Abnormality in Patients With Schizophrenia or Schizoaffective Disorder Treated With Olanzapine
A study testing olanzapine and melatonin in people with Schizophrenia and Schizoaffective Disorder, run by Seattle Institute for Biomedical and Clinical Research at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Schizophrenia, Schizoaffective Disorder, Bipolar Disorder
- What is being tested?
- olanzapine and melatonin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2007to Dec 2024
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
VA Puget Sound Health Care System
Tacoma, Washington, 98493
About this study
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, schizoaffective, or bipolar disorder.
Read the 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.
- Being tested
- olanzapine and melatonin
- Keywords
- schizophrenia, schizoaffective disorder, bipolar disorder, olanzapine, melatonin, obesity, metabolic syndrome
- Medical subject headings
- Schizophrenia, Psychotic Disorders, Bipolar Disorder, Obesity, Metabolic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
olanzapine and melatoninDrug
Also called Olanzapine (Zyprexa)
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.
| Study group | Role | What they receive |
|---|---|---|
| IIA (0.3mg day melatonin) | Experimental | 0.3mg day melatonin Receives: Drug: olanzapine and melatonin |
| IIB (3.0 mg/day melatonin) | Experimental | 3.0 mg/day melatonin Receives: Drug: olanzapine and melatonin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Nocturnal Melatonin Production
Nocturnal melatonin production as estimated by assay of urinary 6-sulfatoxymelatonin (aMT6s) adjusted for creatinine
Measured: 6 and 12 weeks
Secondary outcomes (2)
Weight
weight (measured in kilograms)
Measured: 6 weeks & 12 weeks
Total Cholesterol
Total cholesterol on metabolic blood panel
Measured: 6 weeks & 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2007 (estimated)
- Study startJul 2007
- Primary completionDec 2010
- Study completionDec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Seattle Institute for Biomedical and Clinical Research
- Sponsor type
- University, hospital or other
- Collaborators
- Eli Lilly and Company
- Responsible party
- Sponsor
- Investigators
- Amanda E Wood, PhD, Principal investigator, VA Puget Sound Health Care System; University of Washington
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00512070
- Sponsor's protocol ID
- F1D-MC-X302
- Status last verified
- Nov 2024
- First submitted
- 3 Aug 2007
- Last updated
- 1 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 16710316