Karen M Barlow1,2,3, Brian L Brooks4,2,5,6, Michael J Esser4,2, Adam Kirton4,7,2, Angelo Mikrogianakis4,8, Roger L Zemek9, Frank P MacMaster4,10, Alberto Nettel-Aguirre4,11, Keith Owen Yeates4,2,5, Valerie Kirk4, James S Hutchison12,13, Susan Crawford6, Brenda Turley6, Candice Cameron14, Michael D Hill2, Tina Samuel6, Jeffrey Buchhalter4, Lawrence Richer15, Robert Platt16, Roslyn Boyd3, Deborah Dewey4,11. 1. Department of Pediatrics, Alberta Children's Hospital Research Institute and kbarlow@uq.edu.au. 2. Clinical Neurosciences, Cumming School of Medicine and. 3. Child Health Research Centre, The University of Queensland, Brisbane, Australia. 4. Department of Pediatrics, Alberta Children's Hospital Research Institute and. 5. Psychology, University of Calgary, Calgary, Alberta, Canada. 6. Neuroscience Program, Alberta Children's Hospital, Calgary, Alberta, Canada. 7. Radiology. 8. Emergency Medicine, and. 9. Departments of Pediatrics and Emergency Medicine and Research Institute, Children's Hospital of Eastern Ontario and University of Ottawa, Ottawa, Ontario, Canada. 10. Departments of Psychiatry, Paediatrics, and. 11. Departments of Community Health Sciences. 12. Neurosciences and Mental Health Research Program, Department of Critical Care Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada. 13. Interdepartmental Division of Critical Care Medicine and Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada. 14. Research Pharmacy, Foothills Medical Centre, Alberta Health Services, Calgary, Alberta, Canada. 15. Department of Pediatrics and Women and Children's Health Research Institute, University of Alberta, Edmonton, Alberta, Canada. 16. McGill University, Montreal, Québec, Canada; and.
Abstract
BACKGROUND: Approximately 25% of children with concussion have persistent postconcussive symptoms (PPCS) with resultant significant impacts on quality of life. Melatonin has significant neuroprotective properties, and promising preclinical data suggest its potential to improve outcomes after traumatic brain injury. We hypothesized that treatment with melatonin would result in a greater decrease in PPCS symptoms when compared with a placebo. METHODS: We conducted a randomized, double-blind trial of 3 or 10 mg of melatonin compared with a placebo (NCT01874847). We included youth (ages 8-18 years) with PPCS at 4 to 6 weeks after mild traumatic brain injury. Those with significant medical or psychiatric histories or a previous concussion within the last 3 months were excluded. The primary outcome was change in the total youthself-reported Post-Concussion Symptom Inventory score measured after 28 days of treatment. Secondary outcomes included change in health-related quality of life, cognition, and sleep. RESULTS:Ninety-nine children (mean age: 13.8 years; SD = 2.6 years; 58% girls) were randomly assigned. Symptoms improved over time with a median Post-Concussion Symptom Inventory change score of -21 (95% confidence interval [CI]: -16 to -27). There was no significant effect of melatonin when compared with a placebo in the intention-to-treat analysis (3 mg melatonin, -2 [95% CI: -13 to 6]; 10 mg melatonin, 4 [95% CI: -7 to 14]). No significant group differences in secondary outcomes were observed. Side effects were mild and similar to the placebo. CONCLUSIONS: Children with PPCS had significant impairment in their quality of life. Seventy-eight percent demonstrated significant recovery between 1 and 3 months postinjury. This clinical trial does not support the use of melatonin for the treatment of pediatric PPCS.
RCT Entities:
BACKGROUND: Approximately 25% of children with concussion have persistent postconcussive symptoms (PPCS) with resultant significant impacts on quality of life. Melatonin has significant neuroprotective properties, and promising preclinical data suggest its potential to improve outcomes after traumatic brain injury. We hypothesized that treatment with melatonin would result in a greater decrease in PPCS symptoms when compared with a placebo. METHODS: We conducted a randomized, double-blind trial of 3 or 10 mg of melatonin compared with a placebo (NCT01874847). We included youth (ages 8-18 years) with PPCS at 4 to 6 weeks after mild traumatic brain injury. Those with significant medical or psychiatric histories or a previous concussion within the last 3 months were excluded. The primary outcome was change in the total youth self-reported Post-Concussion Symptom Inventory score measured after 28 days of treatment. Secondary outcomes included change in health-related quality of life, cognition, and sleep. RESULTS: Ninety-nine children (mean age: 13.8 years; SD = 2.6 years; 58% girls) were randomly assigned. Symptoms improved over time with a median Post-Concussion Symptom Inventory change score of -21 (95% confidence interval [CI]: -16 to -27). There was no significant effect of melatonin when compared with a placebo in the intention-to-treat analysis (3 mg melatonin, -2 [95% CI: -13 to 6]; 10 mg melatonin, 4 [95% CI: -7 to 14]). No significant group differences in secondary outcomes were observed. Side effects were mild and similar to the placebo. CONCLUSIONS:Children with PPCS had significant impairment in their quality of life. Seventy-eight percent demonstrated significant recovery between 1 and 3 months postinjury. This clinical trial does not support the use of melatonin for the treatment of pediatric PPCS.
Authors: Cydni N Williams; Cindy T McEvoy; Miranda M Lim; Steven A Shea; Vivek Kumar; Divya Nagarajan; Kurt Drury; Natalia Rich-Wimmer; Trevor A Hall Journal: Children (Basel) Date: 2022-05-19
Authors: Karen M Barlow; Kartik Iyer; Tingting Yan; Alex Scurfield; Helen Carlson; Yang Wang Journal: J Neurotrauma Date: 2021-02-03 Impact factor: 4.869
Authors: Joshua Kamins; Rachel Richards; Bradley J Barney; Christopher Locandro; Christina F Pacchia; Andrew C Charles; Lawrence J Cook; Gerard Gioia; Christopher C Giza; Heidi K Blume Journal: JAMA Netw Open Date: 2021-03-01