PLAY GAME: Post-concussion Syndrome in Youth - Assessing the GABAergic Effects of Melatonin

NCT01874847 | Unknown Phase 2 DMC

• 1 other identifier: TMT-127046
• Study Type: interventional
• Target: 99
• Locations: 1 country
• Sites: 1

Brief Summary

PURPOSE: The long-term goal of this line of research is to develop rational, biologically based evidence for the treatment of post-concussion syndrome (PCS) in children. The objective of this application is to examine the effect of melatonin on the symptoms of PCS and its neurobiology using integrated neurodiagnostic techniques in children. OVERVIEW: PCS is a constellation of clinical symptoms including physical (i.e. headaches), cognitive (i.e. memory), and behavioral disturbances. PCS is associated with significant morbidity in the child and his/her family), and yet there are no evidence-based medical treatments available. This suggests an urgent need to develop novel treatment options to improve outcomes for children suffering from PCS. Melatonin has several relevant mechanisms of action, and neuroprotective effects. Recent research suggests that the explanations for persistent PCS symptoms may be due to alterations in neurotransmissions and neuronal circuitry, particularly involving the dorsolateral prefrontal cortex (DLPFC). Investigators have two specific aims:

1. 1.To determine if treatment with melatonin improves PCS in children following mild traumatic brain injury. Hypothesis: treatment of mTBI children with PCS with 3mg or 10mg of oral melatonin for 28 days will result in a decrease in PCS symptoms as compared with placebo. Effects will be dose-dependent and may be independent of sleep effects. Methods: A randomized double blind, placebo controlled trial (RCT); Outcome measure is a PCS symptom questionnaire. A subsequent RCT will then be performed using the optimal melatonin dose at a second centre.
2. 2.To understand the neurophysiological mechanisms of paediatric PCS and assess any resultant effects of treatment with melatonin. Methods: A case-controlled study within the RCT, using functional MRI and Transcranial Magnetic Stimulation to investigate the neurophysiological properties of paediatric mTBI before and after treatment; Treatment groups from the RCT will be compared with two control groups: i) normal controls and ii) asymptomatic mTBI children.

Conditions

Post-concussion Syndrome; Post-concussive Symptoms; Traumatic Brain Injury; Concussion; Children

Keywords

melatonin; placebo; post-concussion syndrome; mild traumatic brain injury; concussion; treatment; outcome; children; functional magnetic resonance imaging; transcranial magnetic stimulation; sleep

Outcome Measures

Primary Outcomes (1)

• Change on the Post Concussion Symptom Inventory (PCSI)-(8 - 18 years)

  The PCSI is a standardized questionnaire of 26 symptoms provides an overall rating of Post concussion symptoms. It has four specific domains: physical (including headaches), cognitive, emotional (including mood) and fatigue and high level of internal consistency, alpha=0.92. Parent and youth PCSI scores correlate. Low symptom rates are found in normative samples. The version for youth will also be recorded (PCSI-Y). Change in PCSI scores allows us to account for baseline variability and gender.

  Baseline, 4 weeks and 12 weeks

Secondary Outcomes (1)

• Number of Patient's Adverse Events

  1, 2, 3 and 4 weeks

Other Outcomes (3)

• Change on the Child Health Questionnaire (CHQ)

  Baseline, 4 and 12 weeks

• Change on the Behavior Assessment System for Children (BASC)-2 -Parent

  Baseline, 4 and 12 weeks

• Change on the Post Concussion Symptom Inventory (PCSI)- Parent questionnaire

  Baseline, 2 , 4 and 12 weeks

Study Arms (3)

Melatonin 10mg

EXPERIMENTAL

Melatonin 10mg capsule(high dose arm), oral, once at night, given for 28 days

Dietary Supplement: Melatonin

Sugar Pill

PLACEBO COMPARATOR

Sugar Pill, one capsule, once at night, 28 days

Dietary Supplement: Sugar pill

Melatonin 3mg

EXPERIMENTAL

Melatonin 3mg capsule (low dose arm), once, at night, 28 days

Dietary Supplement: Melatonin

Interventions

Melatonin DIETARY_SUPPLEMENT

Melatonin 10mg or 3mg capsule, one will be given at night, for 28 days

Melatonin 10mg; Melatonin 3mg

Sugar pill DIETARY_SUPPLEMENT

Sugar pill will be given, one capsule, once at night, for 28 days

Sugar Pill

Eligibility Criteria

• Age: 8 Years - 19 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Concussion/mild traumatic brain injury trauma with an increase in symptoms (increase in PCS symptoms compared with pre-injury status) at 30 days post injury
• must be able to swallow pills

You may not qualify if:

• Previous significant medical history, or previous concussion within 3 months
• Participant in a natural history study of concussion
• Lactose intolerance, as the placebo contains lactose
• Use of drugs that are likely to affect TMS, fMRI and/or sleep
• Inability to complete questionnaires/evaluation e.g. non-English language

Sponsors & Collaborators

• University of Calgary: lead
• Children's Hospital of Eastern Ontario: collaborator

Study Sites (1)

Alberta Children's Hospital

Calgary, Alberta, T3B6A8, Canada

Location

Related Publications (5)

• Kuczynski A, Crawford S, Bodell L, Dewey D, Barlow KM. Characteristics of post-traumatic headaches in children following mild traumatic brain injury and their response to treatment: a prospective cohort. Dev Med Child Neurol. 2013 Jul;55(7):636-41. doi: 10.1111/dmcn.12152. Epub 2013 Apr 5.

  PMID: 23560811 BACKGROUND

• Barlow KM, Crawford S, Stevenson A, Sandhu SS, Belanger F, Dewey D. Epidemiology of postconcussion syndrome in pediatric mild traumatic brain injury. Pediatrics. 2010 Aug;126(2):e374-81. doi: 10.1542/peds.2009-0925. Epub 2010 Jul 26.

  PMID: 20660554 BACKGROUND

• Barlow KM, Brooks BL, MacMaster FP, Kirton A, Seeger T, Esser M, Crawford S, Nettel-Aguirre A, Zemek R, Angelo M, Kirk V, Emery CA, Johnson D, Hill MD, Buchhalter J, Turley B, Richer L, Platt R, Hutchison J, Dewey D. 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. Trials. 2014 Jul 7;15:271. doi: 10.1186/1745-6215-15-271.

  PMID: 25001947 BACKGROUND

• Iyer KK, Zalesky A, Cocchi L, Barlow KM. Neural Correlates of Sleep Recovery following Melatonin Treatment for Pediatric Concussion: A Randomized Controlled Trial. J Neurotrauma. 2020 Dec 15;37(24):2647-2655. doi: 10.1089/neu.2020.7200. Epub 2020 Sep 14.

  PMID: 32772826 DERIVED

• Barlow KM, Brooks BL, Esser MJ, Kirton A, Mikrogianakis A, Zemek RL, MacMaster FP, Nettel-Aguirre A, Yeates KO, Kirk V, Hutchison JS, Crawford S, Turley B, Cameron C, Hill MD, Samuel T, Buchhalter J, Richer L, Platt R, Boyd R, Dewey D. Efficacy of Melatonin in Children With Postconcussive Symptoms: A Randomized Clinical Trial. Pediatrics. 2020 Apr;145(4):e20192812. doi: 10.1542/peds.2019-2812. Epub 2020 Mar 26.

  PMID: 32217739 DERIVED

Related Links

• PlayGame Trial website

MeSH Terms

Conditions

Post-Concussion Syndrome; Brain Injuries, Traumatic; Brain Concussion

Interventions

Melatonin; Sugars

Condition Hierarchy (Ancestors)

Head Injuries, Closed; Craniocerebral Trauma; Trauma, Nervous System; Nervous System Diseases; Wounds and Injuries; Wounds, Nonpenetrating; Brain Injuries; Brain Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Carbohydrates

Study Officials

• Karen M Barlow, MB.ChB

  Alberta Children's Hospital Research Institute, University of Calgary

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Placebo controlled

Study Record Dates

• First Submitted: June 6, 2013
• First Posted: June 11, 2013
• Study Start: September 1, 2013
• Primary Completion: April 1, 2017
• Study Completion: September 1, 2019
• Last Updated: April 18, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)