Clinical trial NCT01593774: Melatonin for Prevention of Metabolic Side Effects of Olanzapine
Official title: Phase 2 Study of Melatonin Adjunct to Olanzapine for Prevention of Olanzapine-associated Metabolic Side Effects.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Schizophrenia
Keywords: Melatonin
Olanzapine
Metabolic side effects
Psychosis
Hyperlipidemia
Hyperglycemia
Weight gain
Diabetes
Lead sponsor: Guilan University of Medical Sciences
Sponsor class: OTHER
First posted: 2012-05-08
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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 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

Primary outcomes:
measure: Change from baseline in weight at week eight
timeFrame: Baseline and week eight
Secondary outcomes:
measure: Change from baseline in Triglyceride at week 4
timeFrame: Baseline and week 4
measure: Change from baseline in HDL at week 4
timeFrame: Baseline and week 4
measure: Change from baseline in LDL at week 4
timeFrame: Baseline and week 4
measure: Change from baseline in Total Cholesterol at week 4
timeFrame: Baseline and Week 4
measure: Change from baseline in weight at week 4
timeFrame: Baseline and week 4
measure: Change from baseline in Fasting blood sugar at week 4
timeFrame: Baseline and week 4
measure: Change from baseline in blood pressure at week 4
timeFrame: Baseline and week 4
measure: Change from baseline in body mass index (BMI) at week 4
timeFrame: Baseline and week 4
measure: Change from baseline in waist to hip ratio at week 4
timeFrame: Baseline and week 4
measure: Change from baseline in Positive and negative syndrome scale (PANSS) at week 4
timeFrame: Baseline and week 4
measure: Change from baseline in Positive and negative syndrome scale (PANSS) at week 8
timeFrame: Baseline and week 8
measure: Change from baseline in Triglyceride at week 48
timeFrame: Baseline and week 8
measure: Change from baseline in HDL at week 8
timeFrame: Baseline and week 8
measure: Change from baseline in LDL at week 8
timeFrame: Baseline and week 8
measure: Change from baseline in Total Cholesterol at week 8
timeFrame: Baseline and Week 8
measure: Change from baseline in Fasting blood sugar at week 8
timeFrame: Baseline and week 8
measure: Change from baseline in blood pressure at week 8
timeFrame: Baseline and week 8
measure: Change from baseline in body mass index (BMI) at week 8
timeFrame: Baseline and week 8
measure: Change from baseline in waist to hip ratio at week 8
timeFrame: Baseline and week 8
measure: Change from baseline in Insulin at week 8
timeFrame: Baseline and week 8
measure: Number of adverse events at the end of the study in each group
timeFrame: Baseline, week 4, and 8
measure: Changes from baseline in HOMA-IR values at week 8
timeFrame: Baseline and week 8
Other outcomes:
Locations:
city: Rasht
country: Iran, Islamic Republic of
facility: Shafa Psychiatric Hospital
state: Guilan
Study officials:
affiliation: Guilan University of Medical Sciences
name: Mohammad Jafar Modabbernia, MD
role: STUDY_CHAIR
References:
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.
citation: 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.
citation: 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.
citation: 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.