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
1 Alberta Children’s Hospital Research Institute, University of Calgary, Room 293, Heritage Medical Research Building 3330 Hospital Drive NW, Calgary, AB T2N 4N1, Canada
2 Pediatric Emergency Medicine, Children’s Hospital of Eastern Ontario, 01 Smyth Road, Ottawa, Ontario K1H 8L1, Canada
3 Faculty of Kinesiology, 2500 University Drive NW, Calgary, AB T2N 1N4, Canada
4 Hotchkiss Brain Institute, University of Calgary, Health Research Innovation Centre, Room 1A10, 3330 Hospital Drive NW, Calgary T2N 4N1 Alberta Canada
5 Department of Pediatric Neurology, University of Alberta, Room 1D1, 8440 112 Street, Edmonton T6G 2B7 Alberta, Canada
6 Department of Statistics, Montreal Children’s Hospital Research Institute, McGill University, 2300 Tupper Street, Montreal, Quebec H3H 1P3, Canada
7 Department of Pediatrics, Department of Critical Care Medicine, The Hospital for Sick Children, 555 University Ave. 2nd Floor, Atrium - Room 2830A, Toronto, Ontario M5G 1X8, Canada
8 Alberta Children’s Hospital, 2888 Shaganappi Trail NW, Calgary, Alberta T3B 6A8, Canada
Trials 2014, 15:271 doi:10.1186/1745-6215-15-271Published: 7 July 2014
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.
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.
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.
This trial was registered on 6 June 2013 at ClinicalTrials.gov. Registration number: NCT01874847.