Melatonin for Prevention of Metabolic Side Effects of Olanzapine - Full Text View

Purpose

The purpose of this study is to determine whether melatonin can prevent metabolic side effects of olanzapine such as weight gain, elevated glucose concentrations and lipid abnormalities.

Condition	Intervention	Phase
Schizophrenia	Drug: Melatonin Drug: Placebo	Phase 2

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: Prevention
Official Title:	Phase 2 Study of Melatonin Adjunct to Olanzapine for Prevention of Olanzapine-associated Metabolic Side Effects.

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Medicines Hyperglycemia Schizophrenia

Drug Information available for: Melatonin Olanzapine Olanzapine pamoate

U.S. FDA Resources

Further study details as provided by Guilan University of Medical Sciences:

Primary Outcome Measures:

Change from baseline in weight at week eight [ Time Frame: Baseline and week eight ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Change from baseline in Triglyceride at week 4 [ Time Frame: Baseline and week 4 ] [ Designated as safety issue: No ]
Change from baseline in HDL at week 4 [ Time Frame: Baseline and week 4 ] [ Designated as safety issue: No ]
Change from baseline in LDL at week 4 [ Time Frame: Baseline and week 4 ] [ Designated as safety issue: No ]
Change from baseline in Total Cholesterol at week 4 [ Time Frame: Baseline and Week 4 ] [ Designated as safety issue: No ]
Change from baseline in weight at week 4 [ Time Frame: Baseline and week 4 ] [ Designated as safety issue: No ]
Change from baseline in Fasting blood sugar at week 4 [ Time Frame: Baseline and week 4 ] [ Designated as safety issue: No ]
Change from baseline in blood pressure at week 4 [ Time Frame: Baseline and week 4 ] [ Designated as safety issue: No ]
Change from baseline in body mass index (BMI) at week 4 [ Time Frame: Baseline and week 4 ] [ Designated as safety issue: No ]
Change from baseline in waist to hip ratio at week 4 [ Time Frame: Baseline and week 4 ] [ Designated as safety issue: No ]
Change from baseline in Positive and negative syndrome scale (PANSS) at week 4 [ Time Frame: Baseline and week 4 ] [ Designated as safety issue: No ]
Change from baseline in Positive and negative syndrome scale (PANSS) at week 8 [ Time Frame: Baseline and week 8 ] [ Designated as safety issue: No ]
Change from baseline in Triglyceride at week 48 [ Time Frame: Baseline and week 8 ] [ Designated as safety issue: No ]
Change from baseline in HDL at week 8 [ Time Frame: Baseline and week 8 ] [ Designated as safety issue: No ]
Change from baseline in LDL at week 8 [ Time Frame: Baseline and week 8 ] [ Designated as safety issue: No ]
Change from baseline in Total Cholesterol at week 8 [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
Change from baseline in Fasting blood sugar at week 8 [ Time Frame: Baseline and week 8 ] [ Designated as safety issue: No ]
Change from baseline in blood pressure at week 8 [ Time Frame: Baseline and week 8 ] [ Designated as safety issue: No ]
Change from baseline in body mass index (BMI) at week 8 [ Time Frame: Baseline and week 8 ] [ Designated as safety issue: No ]
Change from baseline in waist to hip ratio at week 8 [ Time Frame: Baseline and week 8 ] [ Designated as safety issue: No ]
Change from baseline in Insulin at week 8 [ Time Frame: Baseline and week 8 ] [ Designated as safety issue: No ]
Number of adverse events at the end of the study in each group [ Time Frame: Baseline, week 4, and 8 ] [ Designated as safety issue: Yes ]
Changes from baseline in HOMA-IR values at week 8 [ Time Frame: Baseline and week 8 ] [ Designated as safety issue: No ]

Enrollment:	36
Study Start Date:	May 2012
Study Completion Date:	March 2013
Primary Completion Date:	March 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Melatonin Tablet melatonin 3 mg/day at 9 pm as intervention group for eight week	Drug: Melatonin Tablet melatonin 3 mg/day at 9 pm as intervention group
Placebo Comparator: Placebo Placebo (with the same shape and taste as melatonin) at 9 pm as control group	Drug: Placebo Placebo (with the same shape and taste as melatonin) at 9 pm as control group

Detailed Description:

Atypical antipsychotics including olanzapine are associated with significant metabolic side effects. Animal studies have suggested that melatonin might prevent some of the olanzapine-associated side effects. Melatonin is safe and is widely used as a sleep-promoting complement, and is not associated with side effects seen with other used drugs such as metformin.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age 18-65 year
First episode schizophrenia (DSM-IV-TR)
Ability to take medicine orally
Eligible for starting olanzapine

Exclusion Criteria:

Married women who are at reproductive age
History of taking olanzapine in the recent 3 months
History of allergy or intolerance to olanzapine
History of significant head trauma ( causing loss of consciousness more than 5 minutes or neurological or cognitive sequels)
Liver, kidney, cerebrovascular or cardiovascular disease
Diabetes, metabolic syndrome
Cancer
Using antiepileptic (other than benzodiazepines for sleep) , antihypertensive, anticoagulant, anti-platelet drugs
Using inhibitors or stimulants of hepatic isoenzymes that metabolize melatonin or olanzapine (e.g. omeprazole. rifampin, fluvoxamine, ciprofloxacin, carbamazepine, modafinil)
Delirium
Need for administration of other antipsychotics
Substance abuse

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01593774

Locations

Iran, Islamic Republic of
Shafa Psychiatric Hospital
Rasht, Guilan, Iran, Islamic Republic of, 55599-41939

Sponsors and Collaborators

Guilan University of Medical Sciences

Investigators

Study Chair:

Mohammad Jafar Modabbernia, MD

Guilan University of Medical Sciences

More Information

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. Epub 2006 May 10.

Borba CP, Fan X, Copeland PM, Paiva A, Freudenreich O, Henderson DC. Placebo-controlled pilot study of ramelteon for adiposity and lipids in patients with schizophrenia. J Clin Psychopharmacol. 2011 Oct;31(5):653-8.

Anderson G, Maes M. Melatonin: an overlooked factor in schizophrenia and in the inhibition of anti-psychotic side effects. Metab Brain Dis. 2012 Jun;27(2):113-9. Epub 2012 Apr 25.

Responsible Party:	Mohammad Jafar Modabbernia, Associate Professor of Psychiatry, Guilan University of Medical Sciences
ClinicalTrials.gov Identifier:	NCT01593774 History of Changes
Other Study ID Numbers:	GUMS-9277
Study First Received:	May 6, 2012
Last Updated:	April 8, 2013
Health Authority:	Iran: Ministry of Health

Keywords provided by Guilan University of Medical Sciences:

Melatonin
Olanzapine
Metabolic side effects
Psychosis

Hyperlipidemia
Hyperglycemia
Weight gain
Diabetes

Additional relevant MeSH terms:

Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
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
Tranquilizing Agents
Psychotropic Drugs
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Serotonin Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents

ClinicalTrials.gov processed this record on May 19, 2013