title: A double-blind, placebo-controlled intervention trial of 3 and 10 mg sublingual melatonin for post-concussion syndrome in youths (PLAYGAME): study protocol for a randomized controlled trial.
abstract: BACKGROUND
  By the age of sixteen, one in five children will sustain a mild traumatic brain injury also known as concussion. Our research found that one in seven school children with mild traumatic brain injury suffer post-concussion syndrome symptoms for three months or longer. Post-concussion syndrome is associated with significant disability in the child and his/her family and yet there are no evidence-based medical treatments available. Melatonin has several potential mechanisms of action that could be useful following mild traumatic brain injury, including neuroprotective effects. The aim of this study is to determine if treatment with melatonin improves post-concussion syndrome in youths following mild traumatic brain injury. Our hypothesis is that treatment of post-concussion syndrome following mild traumatic brain injury with 3 or 10 mg of sublingual melatonin for 28 days will result in a decrease in post-concussion syndrome symptoms compared with placebo.
  
  
  METHODS
  Ninety-nine youths with mild traumatic brain injury, aged between 13 and 18 years, who are symptomatic at 30 days post-injury will be recruited. This study will be conducted as a randomized, double blind, placebo-controlled superiority trial of melatonin. Three parallel treatment groups will be examined with a 1:1:1 allocation: sublingual melatonin 3 mg, sublingual melatonin 10 mg, and sublingual placebo. Participants will receive treatment for 28 days. The primary outcome is a change on the Post-Concussion Symptom Inventory (Parent and Youth). The secondary outcomes will include neurobehavioral function, health-related quality of life and sleep. Neurophysiological and structural markers of change, using magnetic resonance imaging techniques and transcranial magnetic stimulation, will also be investigated.
  
  
  CONCLUSIONS
  Melatonin is a safe and well-tolerated agent that has many biological properties that may be useful following a traumatic brain injury. This study will determine whether it is a useful treatment for children with post-concussion syndrome. Recruitment commenced on 4 December 2014.
  
  
  BACKGROUND
  This trial was registered on 6 June 2013 at ClinicalTrials.gov.
  
  
  BACKGROUND
  NCT01874847.
authors.affiliation: Alberta Children's Hospital Research Institute, University of Calgary, Room 293, Heritage Medical Research Building 3330 Hospital Drive NW, Calgary, AB T2N 4N1, Canada. Karen.barlow@albertahealthservices.ca.
authors.forename: Karen M
authors.initials: KM
authors.lastname: Barlow
authors.forename: Brian L
authors.initials: BL
authors.lastname: Brooks
authors.forename: Frank P
authors.initials: FP
authors.lastname: MacMaster
authors.forename: Adam
authors.initials: A
authors.lastname: Kirton
authors.forename: Trevor
authors.initials: T
authors.lastname: Seeger
authors.forename: Michael
authors.initials: M
authors.lastname: Esser
authors.forename: Susan
authors.initials: S
authors.lastname: Crawford
authors.forename: Alberto
authors.initials: A
authors.lastname: Nettel-Aguirre
authors.forename: Roger
authors.initials: R
authors.lastname: Zemek
authors.forename: Mikrogianakis
authors.initials: M
authors.lastname: Angelo
authors.forename: Valerie
authors.initials: V
authors.lastname: Kirk
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Emery
authors.forename: David
authors.initials: D
authors.lastname: Johnson
authors.forename: Michael D
authors.initials: MD
authors.lastname: Hill
authors.forename: Jeff
authors.initials: J
authors.lastname: Buchhalter
authors.forename: Brenda
authors.initials: B
authors.lastname: Turley
authors.forename: Lawrence
authors.initials: L
authors.lastname: Richer
authors.forename: Robert
authors.initials: R
authors.lastname: Platt
authors.forename: Jamie
authors.initials: J
authors.lastname: Hutchison
authors.forename: Deborah
authors.initials: D
authors.lastname: Dewey
mesh_terms: D000286:Administration, Sublingual; D000293:Adolescent; D002985:Clinical Protocols; D004311:Double-Blind Method; D006801:Humans; D008550:Melatonin / Q000008:administration & dosage*; D017063:Outcome Assessment, Health Care; D038223:Post-Concussion Syndrome / Q000188:drug therapy*; D018401:Sample Size
chemical_list: D008550:Melatonin