title: Protocol for a randomized, double blind, placebo controlled, crossover trial of Melatonin for treatment of Nocturia in adults with Multiple Sclerosis (MeNiMS).
abstract: BACKGROUND
  Nocturia (the symptom of needing to wake up to pass urine) is common in progressive Multiple Sclerosis (MS) patients. Moderate-to-severe nocturia affects quality of life, can exacerbate fatigue and may affect capacity to carry out daily activities. Melatonin is a natural hormone regulating circadian cycles, released by the pineal gland at night-time, and secretion is impaired in MS. Melatonin levels can be supplemented by administration in tablet form at bedtime. The aim of this study is to evaluate the effect of melatonin on mean number of nocturia episodes per night in MS patients. Secondary outcome measures will assess impact upon quality of life, urinated volumes, lower urinary tract symptoms (LUTS), cognition, sleep quality and sleep disturbance of partners.
  
  
  METHODS
  A randomized, double blind, placebo controlled, crossover trial consisting of two, six week treatment phases (active drug melatonin 2 mg or placebo), with a 1 month wash-out period in between. The primary outcome (change in nocturia episodes per night) in this two arm, two treatment, two period crossover design, will be objectively measured using frequency volume charts (FVC) at baseline and following both treatment phases. Questionnaires will be used to assess quality of life, sleep quality, safety and urinary tract symptoms. Qualitative interviews of participants and partners will explore issues including quality of life, mechanisms of sleep disturbance and impact of nocturia on partners.
  
  
  CONCLUSIONS
  This study will evaluate whether melatonin reduces the frequency of nocturia episodes in MS patients, and therefore whether 'Circadin' has the potential to reduce LUTS and fatigue, and improve cognition and overall quality of life.
  
  
  BACKGROUND
  (EudraCT reference) 2012-00418321 registered: 25/01/13. ISRCTN Registry: ISRCTN38687869.
authors.affiliation: Bristol Urological Institute, North Bristol NHS Trust, Southmead Hospital, Bristol, BS10 5NB, UK.
authors.forename: D
authors.initials: D
authors.lastname: Delgado
authors.affiliation: Department of Neurology, North Bristol NHS Trust, Southmead Hospital, Bristol, UK.|School of Clinical Sciences, University of Bristol, Bristol, UK.
authors.forename: L
authors.initials: L
authors.lastname: Canham
authors.affiliation: Bristol Urological Institute, North Bristol NHS Trust, Southmead Hospital, Bristol, BS10 5NB, UK.
authors.forename: N
authors.initials: N
authors.lastname: Cotterill
authors.affiliation: Department of Neurology, North Bristol NHS Trust, Southmead Hospital, Bristol, UK.
authors.forename: D
authors.initials: D
authors.lastname: Cottrell
authors.affiliation: Bristol Urological Institute, North Bristol NHS Trust, Southmead Hospital, Bristol, BS10 5NB, UK. Marcus.Drake@bui.ac.uk.|School of Clinical Sciences, University of Bristol, Bristol, UK. Marcus.Drake@bui.ac.uk.
authors.forename: M J
authors.initials: MJ
authors.lastname: Drake
authors.affiliation: Bristol Urological Institute, North Bristol NHS Trust, Southmead Hospital, Bristol, BS10 5NB, UK.
authors.forename: K
authors.initials: K
authors.lastname: Inglis
authors.affiliation: Bristol Urological Institute, North Bristol NHS Trust, Southmead Hospital, Bristol, BS10 5NB, UK.
authors.forename: D
authors.initials: D
authors.lastname: Owen
authors.affiliation: University of West of England, Bristol, UK.
authors.forename: P
authors.initials: P
authors.lastname: White
mesh_terms: D000328:Adult; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000494:pharmacology*; D002985:Clinical Protocols; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000494:pharmacology*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications*; D053158:Nocturia / Q000188:drug therapy* / Q000209:etiology; D017063:Outcome Assessment, Health Care; D011788:Quality of Life
chemical_list: D002492:Central Nervous System Depressants; D008550:Melatonin
keywords: Cognition; LUTS; Melatonin; Multiple Sclerosis; Nocturia