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

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. 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. 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.

SIGNIFICANCE: This study has the potential to 1) provide a safe and effective treatment for PCS and 2) will provide valuable information about the neurophysiological properties of the brain associated with PCS following mTBI in children and how these change with symptom resolution.

Conditions

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

Interventions

DIETARY_SUPPLEMENT

Melatonin

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

DIETARY_SUPPLEMENT

Sugar pill

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

Sponsors & Collaborators

• Children's Hospital of Eastern Ontario

  collaborator OTHER

• University of Calgary

  lead OTHER

Principal Investigators

• Karen M Barlow, MB.ChB · Alberta Children's Hospital Research Institute, University of Calgary

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

8 Years

Max Age

19 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2013-09-30

Primary Completion

2017-04-30

Completion

2019-09-30

Countries

• Canada

Study Locations