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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by University of Calgary
Sponsor:
Collaborator:
Children's Hospital of Eastern Ontario
Information provided by (Responsible Party):
Dr. Karen Barlow, University of Calgary
ClinicalTrials.gov Identifier:
NCT01874847
First received: June 6, 2013
Last updated: November 25, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Post-concussion Syndrome
Post-concussive Symptoms
Traumatic Brain Injury
Concussion
Children
Dietary Supplement: Melatonin
Dietary Supplement: Sugar pill
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: PLAY GAME: Post-concussion Syndrome Affecting Youth: GABAergic Effects of Melatonin. A Randomized Double-blind Placebo-controlled Trial of MELATONIN

Resource links provided by NLM:


Further study details as provided by University of Calgary:

Primary Outcome Measures:
  • Change on the Post Concussion Symptom Inventory (PCSI)- Youth (13 - 18 years) [ Time Frame: Baseline, 4 weeks and 12 weeks ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Number of Patient's Adverse Events [ Time Frame: 1, 2, 3 and 4 weeks ] [ Designated as safety issue: Yes ]

Other Outcome Measures:
  • Change on the Child Health Questionnaire (CHQ) [ Time Frame: Baseline, 4 and 12 weeks ] [ Designated as safety issue: No ]
    Parent and child rating of functional impairment will be obtained using the 50-item Child Health Questionnaire, parent CHQ-Parent Form (PF)50 and child, CHQ-Child Form (CF)87. The reliability and validity is established in TBI and PCS.

  • Change on the Behavior Assessment System for Children (BASC)-2 -Parent [ Time Frame: Baseline, 4 and 12 weeks ] [ Designated as safety issue: No ]

    BASC-2 is a standardized parent report measure of child behavior consisting of 150 items. It provides an indication of internalizing and externalizing behaviour (e.g., anxiety, depression). Items are rated using true-false, or a 4-point ordinal scale.

    The internal consistency for the composite subscales range from .87 to .96 and test-retest reliability is high, ranging from .81 to .96 (10-20 minutes) (


  • Change on the Post Concussion Symptom Inventory (PCSI)- Parent questionnaire [ Time Frame: Baseline, 2 , 4 and 12 weeks ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 100
Study Start Date: September 2013
Estimated Study Completion Date: September 2019
Estimated Primary Completion Date: August 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Melatonin 10mg
Melatonin 10mg capsule(high dose arm), oral, once at night, given for 28 days
Dietary Supplement: Melatonin
Melatonin 10mg or 3mg capsule, one will be given at night, for 28 days
Placebo Comparator: Sugar Pill
Sugar Pill, one capsule, once at night, 28 days
Dietary Supplement: Sugar pill
Sugar pill will be given, one capsule, once at night, for 28 days
Experimental: Melatonin 3mg
Melatonin 3mg capsule (low dose arm), once, at night, 28 days
Dietary Supplement: Melatonin
Melatonin 10mg or 3mg capsule, one will be given at night, for 28 days

  Eligibility

Ages Eligible for Study:   13 Years to 19 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • Previous significant medical history, or previous concussion within 12 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
  • Claustrophobia/inability to tolerate MRI including ferromagnetic implants
  • Contraindications to TMS (including history of seizures, unexplained loss of consciousness(LOC),metal in the head and/or implanted brain medical devices, cardiac pacemaker, etc.)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01874847

Contacts
Contact: Brenda Turley, BA 1-403-955-3184 brenda.turley@albertahealthservices.ca

Locations
Canada, Alberta
Alberta Children's Hospital Recruiting
Calgary, Alberta, Canada, T3B6A8
Contact: Brenda Turley, BA         
Contact: Karen Barlow, MD         
Sub-Investigator: Adam Kirton, MD         
Sub-Investigator: Frank McMaster, PhD         
Sub-Investigator: Brian Brooks, PhD         
Sub-Investigator: Valerie Kirk, MD         
Sub-Investigator: Deborah Dewey, PhD         
Sub-Investigator: David Johnson, MD         
Sub-Investigator: Angelo Mikrogianakis, MD         
Sub-Investigator: Alberto Nettel-Aguirre, PhD         
Sub-Investigator: Roger Zemek, MD         
Sub-Investigator: Susan Crawford, MSc         
Sub-Investigator: Jeff Buchhalter, MD         
Sub-Investigator: Michael Hill, MD         
Sponsors and Collaborators
University of Calgary
Children's Hospital of Eastern Ontario
Investigators
Principal Investigator: Karen M Barlow, MB.ChB Alberta Children's Hospital Research Institute, University of Calgary
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Dr. Karen Barlow, Principal Investigator, University of Calgary
ClinicalTrials.gov Identifier: NCT01874847     History of Changes
Other Study ID Numbers: TMT-127046
Study First Received: June 6, 2013
Last Updated: November 25, 2013
Health Authority: Canada: Health Canada

Keywords provided by University of Calgary:
melatonin
placebo
post-concussion syndrome
mild traumatic brain injury
concussion
treatment
outcome
children
functional magnetic resonance imaging
transcranial magnetic stimulation
sleep

Additional relevant MeSH terms:
Brain Concussion
Brain Injuries
Post-Concussion Syndrome
Syndrome
Brain Diseases
Central Nervous System Diseases
Craniocerebral Trauma
Disease
Head Injuries, Closed
Nervous System Diseases
Pathologic Processes
Trauma, Nervous System
Wounds and Injuries
Wounds, Nonpenetrating
Melatonin
Antioxidants
Central Nervous System Agents
Central Nervous System Depressants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014