Melatonin for Prevention of Metabolic Side Effects of Olanzapine

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

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.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Melatonin; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in weight at week eight	Baseline and week eight

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in Triglyceride at week 4	Baseline and week 4
Change from baseline in HDL at week 4	Baseline and week 4
Change from baseline in LDL at week 4	Baseline and week 4
Change from baseline in Total Cholesterol at week 4	Baseline and Week 4
Change from baseline in weight at week 4	Baseline and week 4
Change from baseline in Fasting blood sugar at week 4	Baseline and week 4
Change from baseline in blood pressure at week 4	Baseline and week 4
Change from baseline in body mass index (BMI) at week 4	Baseline and week 4
Change from baseline in waist to hip ratio at week 4	Baseline and week 4
Change from baseline in Positive and negative syndrome scale (PANSS) at week 4	Baseline and week 4
Change from baseline in Positive and negative syndrome scale (PANSS) at week 8	Baseline and week 8
Change from baseline in Triglyceride at week 48	Baseline and week 8
Change from baseline in HDL at week 8	Baseline and week 8
Change from baseline in LDL at week 8	Baseline and week 8
Change from baseline in Total Cholesterol at week 8	Baseline and Week 8
Change from baseline in Fasting blood sugar at week 8	Baseline and week 8
Change from baseline in blood pressure at week 8	Baseline and week 8
Change from baseline in body mass index (BMI) at week 8	Baseline and week 8
Change from baseline in waist to hip ratio at week 8	Baseline and week 8
Change from baseline in Insulin at week 8	Baseline and week 8
Number of adverse events at the end of the study in each group	Baseline, week 4, and 8
Changes from baseline in HOMA-IR values at week 8	Baseline and week 8

Collaborators and Investigators

• Sponsor: Guilan University of Medical Sciences
• Investigators: Study Chair: Mohammad Jafar Modabbernia, MD, Guilan University of Medical Sciences

Publications and helpful links

General 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.
• 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. doi: 10.1097/JCP.0b013e31822bb573.
• 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. doi: 10.1007/s11011-012-9307-9. Epub 2012 Apr 25.
• Modabbernia A, Heidari P, Soleimani R, Sobhani A, Roshan ZA, Taslimi S, Ashrafi M, Modabbernia MJ. Melatonin for prevention of metabolic side-effects of olanzapine in patients with first-episode schizophrenia: randomized double-blind placebo-controlled study. J Psychiatr Res. 2014 Jun;53:133-40. doi: 10.1016/j.jpsychires.2014.02.013. Epub 2014 Feb 24.

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (ACTUAL): March 1, 2013
• Study Completion (ACTUAL): March 1, 2013

Study Registration Dates

• First Submitted: May 6, 2012
• First Submitted That Met QC Criteria: May 7, 2012
• First Posted (ESTIMATE): May 8, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): April 9, 2013
• Last Update Submitted That Met QC Criteria: April 8, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: Diabetes; Psychosis; Melatonin; Hyperglycemia; Hyperlipidemia; Olanzapine; Weight gain; Metabolic side effects
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Protective Agents; Antioxidants; Melatonin
• Other Study ID Numbers: GUMS-9277