title: Impact of Melatonin on Motor, Cognitive and Neuroimaging Indices in Patients with Multiple Sclerosis.
abstract: A series of preclinical and clinical studies have shown the immunomodulatory effect of  melatonin, especially in the state of chronic inflammation. A double-blind, randomized, parallel-group, placebo-controlled clinical trial was designed to study the tolerability and efficacy of supplemental therapy with melatonin (3 mg/day) in comparison to placebo in relapsing-remitting MS (RRMS) patients receiving once weekly interferon beta. Patients were followed up for 12 months. Primary outcomes consisted of the number of relapses, change in Extended Disability Status Scale (EDSS), and the number and volume of new T2 and gadolinium-enhancing brain lesions. Secondary outcomes included change in performance on Multiple Sclerosis Functional Composite (MSFC) as well as change in fatigue and depression. The outcomes were evaluated every three months. Twenty-six patients (13 in each group) were recruited in the study. All participants, except for one patient in the placebo group, completed the study. No patient reported serious adverse events. There was no significant difference either in primary or secondary outcomes between melatonin and placebo arm. However, a trend for beneficial effect was observed for melatonin on change in MSFC performance and the cognitive subscore of the Modified Fatigue Impact Scale (p=0.05 and 0.006, respectively, not corrected for multiple comparisons). We found no significant effect for treatment with melatonin on measures of clinical and functional disability and development of brain lesions in our small sample-size study. Studies with higher statistical power and longer follow up are needed to further evaluate the potential immunomodulatory effect of melatonin in RRMS treatment.
authors.affiliation: Iranian Center of Neurological Research, Tehran University of Medical Sciences, Tehran, Iran AND Interdisciplinary Neuroscience Research Program, Tehran University of Medical Sciences, Tehran, Iran AND Kimel Family Translational Imaging-Genetics Laboratory, Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
authors.forename: Tina
authors.initials: T
authors.lastname: Roostaei
authors.affiliation: MS Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran AND Department of Neurology, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad Ali
authors.initials: MA
authors.lastname: Sahraian
authors.affiliation: Iranian Center of Neurological Research, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Sara
authors.initials: S
authors.lastname: Hajeaghaee
authors.affiliation: Iranian Center of Neurological Research, Tehran University of Medical Sciences, Tehran, Iran AND Interdisciplinary Neuroscience Research Program, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Taha
authors.initials: T
authors.lastname: Gholipour
authors.affiliation: Iranian Center of Neurological Research, Tehran University of Medical Sciences, Tehran, Iran AND Department of Neurology, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mansoureh
authors.initials: M
authors.lastname: Togha
authors.affiliation: Iranian Center of Neurological Research, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Bahaadin
authors.initials: B
authors.lastname: Siroos
authors.affiliation: Iranian Center of Neurological Research, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Sepideh
authors.initials: S
authors.lastname: Mansouri
authors.affiliation: Iranian Center of Neurological Research, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Mohammadshirazi
authors.affiliation: Iranian Center of Neurological Research, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Aghazadeh Alasti
authors.affiliation: Iranian Center of Neurological Research, Tehran University of Medical Sciences, Tehran, Iran AND Department of Neurology, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Harirchian
mesh_terms: D000328:Adult; D001921:Brain / Q000187:drug effects*; D003071:Cognition / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D008297:Male; D008550:Melatonin / Q000009:adverse effects / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D059906:Neuroimaging
chemical_list: D007155:Immunologic Factors; D008550:Melatonin
keywords: Immunomodulation; Melatonin; Multiple sclerosis