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Trial registered on ANZCTR


Registration number
ACTRN12617000418370
Ethics application status
Approved
Date submitted
9/03/2017
Date registered
23/03/2017
Date last updated
7/08/2019
Date data sharing statement initially provided
26/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Active intervention to treat persistent post-concussion symptoms in children and adolescents
Scientific title
Developing an evidence-base for preventing and treating delayed symptoms of concussion in children and adolescents: a randomised controlled clinical trial
Secondary ID [1] 291407 0
APP1040270
Universal Trial Number (UTN)
U1111-1194-0683
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Concussion 302427 0
Condition category
Condition code
Injuries and Accidents 301996 301996 0 0
Other injuries and accidents
Neurological 302013 302013 0 0
Other neurological disorders
Physical Medicine / Rehabilitation 302014 302014 0 0
Other physical medicine / rehabilitation

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention group Concussion Essentials (CE) will receive up to 8 weeks (8 scheduled, 1 hour sessions) of an individualised multimodal intervention, provided by trained clinicians. CE incorporates three modules designed to treat symptoms within the key PPCS clusters: common, physical, psychological. For each module, treatment procedures will be clearly detailed and manualised to ensure consistency.
1. Concussion essentials module: Participants will receive education and advice addressing symptoms commonly experienced by children with PPCS.
2. Physical module: Participants will receive treatment comprising vestibular, ocular-motor and cervical treatment, and supported graded return to aerobic exercise delivered by a clinician under supervision of a neurophysiotherapist experienced in concussion management.
3. Psychological module: Participants will receive evidence-based cognitive behaviour therapy (CBT), the Creating Opportunities for Personal Empowerment (COPE) program, adapted for concussion, and targeting emotional symptoms (anxiety, depression, avoidance), delivered by a clinician or clinical psychology student supervised by an experienced psychologist.
Intervention code [1] 297444 0
Treatment: Other
Intervention code [2] 297445 0
Rehabilitation
Intervention code [3] 297467 0
Behaviour
Comparator / control treatment
Usual Care (UC) group. Participants in this arm of the study will receive routine care and follow-up as provided in the RCH or community. Health service utilisation will be captured via survey, CVDL and Medicare/PBS data.
Control group
Active

Outcomes
Primary outcome [1] 301419 0
Post concussion symptoms as measured by the Post Concussion Symptom Inventory (PCSI),
Timepoint [1] 301419 0
Recruitment (presentation to the ED or via a referral network), screening (10 days post-injury), baseline (2 weeks + up to 7 days post-injury), the post-intervention assessment (3 months post-injury), and monitored every week during the intervention.
Secondary outcome [1] 332581 0
Composite of common, physical, psychological PPCS as assessed by the PCSI-P.
Timepoint [1] 332581 0
assessed at baseline (2 weeks + up to 7 days post-injury), and post-intervention (3 months post-injury)
Secondary outcome [2] 332582 0
Return to normal activity (school, sports, leisure activity) return to pre-concussion activity as assessed by parent report on study questionnaire.
Timepoint [2] 332582 0
assessed at baseline (2 weeks + up to 7 days post-injury), and post-intervention (3 months post-injury)
Secondary outcome [3] 332583 0
Pediatric Quality of Life Inventory (PedsQL): measure of health related quality of life (HRQOL); physical, emotional, social, school functioning.
Timepoint [3] 332583 0
assessed at baseline (2 weeks + up to 7 days post-injury), and post-intervention (3 months post-injury)
Secondary outcome [4] 332677 0
Health economy measures: Child Health Utility 9D (CHU-9D): measures HRQOL for use in cost utility analyses. Linked health service utilisation and cost data from hospitals and Medicare will be sought, providing data on use and cost of general practice, physiotherapy, mental health and pharmaceuticals. Cost of lost parental employment, childcare, travel, accommodation and school absenteeism will be obtained through parent survey.
Timepoint [4] 332677 0
assessed at baseline (2 weeks + up to 7 days post-injury), and post-intervention (3 months post-injury)
Secondary outcome [5] 354376 0
Domain specific outcome (13) Anxiety will be assessed by the Revised Children’s Anxiety and Depression Scale – Child, Short Version (RCADS-25),
Timepoint [5] 354376 0
assessed at baseline (2 weeks + up to 7 days post-injury), and post-intervention (3 months post-injury)
Secondary outcome [6] 354377 0
Domain specific outcome (15) Children's behavioural and emotional problems will be assessed by The Strengths and Difficulties Questionnaire (SDQ)
Timepoint [6] 354377 0
assessed at baseline (2 weeks + up to 7 days post-injury), and post-intervention (3 months post-injury)
Secondary outcome [7] 354378 0
Domain specific outcome (1)
Sleep habits will be measured using the Child Sleep Hygiene Scale or Adolescent Sleep Hygiene Scale.
Timepoint [7] 354378 0
assessed at baseline (2 weeks + up to 7 days post-injury), and post-intervention (3 months post-injury)
Secondary outcome [8] 354379 0
Domain specific outcome (2)
Physical activity will be captured with the PROMIS Pediatric Short Form v1.0 - Physical Activity 8a.
Timepoint [8] 354379 0
assessed at baseline (2 weeks + up to 7 days post-injury), and post-intervention (3 months post-injury)
Secondary outcome [9] 354380 0
Domain specific outcome (3)
Fatigue will be measured by the PROMIS Pediatric Short Form v2.0 - Fatigue 10a.

Timepoint [9] 354380 0
assessed at baseline (2 weeks + up to 7 days post-injury), and post-intervention (3 months post-injury)
Secondary outcome [10] 354381 0
Domain specific outcome (4)
Pain will be assessed by the Faces Pain Scale Revised (FPS-R).
Timepoint [10] 354381 0
assessed at baseline (2 weeks + up to 7 days post-injury), and post-intervention (3 months post-injury)
Secondary outcome [11] 354382 0
Domain specific outcome (5)
Exercise tolerance will be assessed using the Treadmill Sub-Maximal Test.
Timepoint [11] 354382 0
assessed at baseline (2 weeks + up to 7 days post-injury), and post-intervention (3 months post-injury)
Secondary outcome [12] 354383 0
Domain specific outcome (6)
Postural stability will be measured by the Balance Error Scoring System (BESS).
Timepoint [12] 354383 0
assessed at baseline (2 weeks + up to 7 days post-injury), and post-intervention (3 months post-injury)
Secondary outcome [13] 354384 0
Domain specific outcome (10)
Deep cervical muscular function will be assessed via the Motor Control Assessment of Deep Cervical Flexors.
Timepoint [13] 354384 0
assessed at baseline (2 weeks + up to 7 days post-injury), and post-intervention (3 months post-injury)
Secondary outcome [14] 354385 0
Domain specific (7)
Response to ocular and vestibular stimulation will be measured by the Vestibular/Ocular Motor Screen (VOMS).
Timepoint [14] 354385 0
assessed at baseline (2 weeks + up to 7 days post-injury), and post-intervention (3 months post-injury)
Secondary outcome [15] 354386 0
Domain specific (8)
The integrity of the vestibular system will be assessed by the Dynamic Visual Acuity Test (DVA).
Timepoint [15] 354386 0
assessed at baseline (2 weeks + up to 7 days post-injury), and post-intervention (3 months post-injury)
Secondary outcome [16] 354387 0
Domain specific (9)
The integrity of the peripheral vestibular system will be assessed by the Head Thrust Test (HTT).
Timepoint [16] 354387 0
assessed at baseline (2 weeks + up to 7 days post-injury), and post-intervention (3 months post-injury)
Secondary outcome [17] 354388 0
Domain specific (11)
Cervicogenic dizziness will be assessed with the Cervical Flexion/Rotation Test (CRF).
Timepoint [17] 354388 0
assessed at baseline (2 weeks + up to 7 days post-injury), and post-intervention (3 months post-injury)
Secondary outcome [18] 354389 0
Domain specific (12)
Smooth pursuit of eye movements will be assessed by the Smooth Pursuit Neck Torsion Test (SPNTT).
Timepoint [18] 354389 0
assessed at baseline (2 weeks + up to 7 days post-injury), and post-intervention (3 months post-injury)
Secondary outcome [19] 354390 0
Domain specific (14) Depression will be measured by the Revised Children’s Anxiety and Depression Scale – Child, Short Version (RCADS-25) and the PROMIS Emotional Distress - Depression Pediatric Item Bank
Timepoint [19] 354390 0
assessed at baseline (2 weeks + up to 7 days post-injury), and post-intervention (3 months post-injury)
Secondary outcome [20] 354391 0
Domain specific (16)
Parent mental health will be assessed by the Kessler Psychological Distress Scale (K10).
Timepoint [20] 354391 0
assessed at baseline (2 weeks + up to 7 days post-injury), and post-intervention (3 months post-injury)
Secondary outcome [21] 354392 0
Domain specific (17)
Parent stress will be measured by the Parent Stress Scale (PSS).
Timepoint [21] 354392 0
assessed at baseline (2 weeks + up to 7 days post-injury), and post-intervention (3 months post-injury)
Secondary outcome [22] 373623 0
Domain specific (18) Child cognition will be assessed using the Rey Auditory Verbal Learning Task (RAVLT), digit span and coding from the Wechsler Intelligence Scale for Children, 5th edition (WISC-V), and the contingency naming test (CNT)
Timepoint [22] 373623 0
assessed at baseline (2 weeks + up to 7 days post-injury), and post-intervention (3 months post-injury)
Secondary outcome [23] 373624 0
Domain specific (19) Genuine effort will be assessed using the Test of Memory Malingering (TOMM)
Timepoint [23] 373624 0
assessed at baseline (2 weeks + up to 7 days post-injury), and post-intervention (3 months post-injury)

Eligibility
Key inclusion criteria
• Age between 8-18 years (at time of randomisation)
• History of concussion up to 10 days prior to ED presentation or referral
• Concussion diagnosis will be confirmed by;Evidence of a blow to the head or impulsive force transmitted to the head; One or more of the following:
Symptoms
• Somatic (e.g., headaches)
• Cognitive (e.g., feeling like in a fog)
• Emotional symptoms (e.g., lability)
Physical signs
• Loss of consciousness
• Amnesia
• Neurological deficit
Balance impairment (e.g., gait unsteadiness)
Behavioural changes (e.g., irritability)
Cognitive impairment (e.g., slowed reaction times)
Sleep/wake disturbance (e.g., somnolence, drowsiness)
Glasgow Coma Score (GCS) 13-15
PPCS at 2 (+ up to 7 days)weeks’ post-injury
PPCS will be defined as endorsement >= 2 PCS on the PCSI, over and above those endorsed pre-injury at the baseline assessment
Minimum age
8 Years
Maximum age
18 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients meeting any of the following criteria will be excluded from the study:

Injury related:
o Unknown time or mechanism of injury
o Non-accidental injury
o Head injury secondary to faint/collapse/seizure
o Structural brain injury on conventional neuroimaging (CT or MRI)
o Multiple trauma
o Cervical spine injury (clinical and/or radiological)
Pre-existing conditions:
o Congenital neuro-ophthalmological or vestibular dysfunction
o Central neurological conditions (e.g., stroke, uncontrolled or unmanaged epilepsy,
moderate to severe brain injury)
o Severe mental health history (e.g., actively suicidal, substance abuse, bipolar or
psychotic disorders)
Researcher judgement of inability to complete study program:
o Complex psychosocial history (e.g., family violence, child protection involvement, etc.)
o Pre-existing developmental disorders (not in mainstream school, or in mainstream
school with a teaching aide)
o Insufficient English to complete study requirements
o Inability to attend on-site visits

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Randomisation to CE or or UC will be in a 1:1 ratio. In order to ensure that PCS profiles are similar in each of the treatment groups, prior to randomisation, participants will be stratified by age and sex (3 age-groups). These groups will be randomised separately to CE or UC. The randomisation sequences will be computer-generated with variable block sizes, in order to reduce the risk of allocation bias. The study statistician will have no contact with the participants.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The primary outcome is the proportion of participants with delayed recovery, at, or prior to completion of, intervention. Participants will be considered fully recovered if there is less than or equal to 1 difference in severity for all items on the PCSI-P, compared to pre-injury PCSI-P ratings. Our data suggests that a 46.6% reduction in symptomatic children occurs from 4 weeks post-injury to 3 months. To establish effectiveness of the trial, we would expect to observe at least a 50% decrease in those with delayed recovery (46.6% UC vs 23.3% CE). With a 90% power and 5% error level, we would require a total sample size of 172, with two equal groups of 86. Our data also indicates an expected loss to follow up of 20%, and so we will aim to recruit 216 participants. With data on 86 per group, we will have 90% power to find a difference of ~0.4SD on secondary continuous outcomes (incl. PCSI domains, PedsQL, CHU-9D, common, physical and psychological function outcomes), and ~23% absolute difference between groups in the percentage who return to school/sport.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 295880 0
Charities/Societies/Foundations
Name [1] 295880 0
The Robert C Bulley Trust/Royal Children's Hospital Foundation.
Address [1] 295880 0
2/48 Flemington Rd
Parkville VIC 3052
Australia
Country [1] 295880 0
Australia
Primary sponsor type
Individual
Name
Prof Vicki Anderson
Address
Royal Children's Hospital
50 Flemington Rd, Parkville VIC 3052
Australia
Country
Australia
Secondary sponsor category [1] 294741 0
Individual
Name [1] 294741 0
A/Prof Franz Babl
Address [1] 294741 0
Royal Children's Hospital
50 Flemington Rd, Parkville VIC 3052
Australia
Country [1] 294741 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297159 0
Royal Children's Hospital Human Research Ethics Committee
Ethics committee address [1] 297159 0
50 Flemington Rd
Parkville VIC 3052
Australia
Ethics committee country [1] 297159 0
Australia
Date submitted for ethics approval [1] 297159 0
01/11/2017
Approval date [1] 297159 0
18/08/2017
Ethics approval number [1] 297159 0
HREC 37100

Summary
Brief summary
By age 10, 1 in 5 children (~51,000 Australian children) will sustain a concussion and present with post-concussive symptoms (PCS) requiring medical treatment. Many children and youth recover rapidly from these symptoms and are symptom free and returned to pre-injury activities within 4 weeks. In contrast, ~40% of children suffer ‘persisting PCS’ (PPCS), defined as 2 or more PCS lasting more than 4 weeks. This group of children have limited tolerance for routine academic, sport/leisure and social activities and are unable to return safely to these activities. Despite their debilitating impact, intervention trials addressing PPCS in children are lacking. We propose a randomised trial of a novel multimodal intervention to reduce the burden of debilitating PPCS for the ~40% of children who experience delayed recovery after concussion. Participants with PPCS at 2-3 weeks post-injury will be recruited and randomised to either active (CE) or usual care (UC) interventions, which will be delivered over up to 8 sessions between 4 – 12 weeks post-injury. The primary aim of the CE is to reduce the number and severity of PPCS. We propose the following hypotheses:

Hypothesis 1: Compared to the UC, children in the CE will have a clinically significant reduction in number and severity of PPCS by treatment completion

Hypothesis 2: Compared to the UC, children in the CE intervention will have a significantly higher proportion of children who, at treatment completion, have:
2.1 Demonstrated reduction in PPCS across all clusters: generic, physical, psychological
2.2 Returned to normal activity (school, sports, leisure activities)
2.3 Improved physical and psychosocial quality of life
2.4 Lower rate of utilisation of health services
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 73178 0
Prof Vicki Anderson
Address 73178 0
The Royal Children's Hospital
50 Flemington Rd Parkville VIC 3052 Australia
Country 73178 0
Australia
Phone 73178 0
+61393454679
Fax 73178 0
Email 73178 0
Vicki.Anderson@rch.org.au
Contact person for public queries
Name 73179 0
Dr Michael Takagi
Address 73179 0
Murdoch Children's Research Institute
50 Flemington Rd Parkville VIC 3052
Country 73179 0
Australia
Phone 73179 0
+61 3 9936 6615
Fax 73179 0
Email 73179 0
takecare@mcri.edu.au
Contact person for scientific queries
Name 73180 0
Dr Michael Takagi
Address 73180 0
Murdoch Children's Research Institute
50 Flemington Rd Parkville VIC 3052
Country 73180 0
Australia
Phone 73180 0
+61 3 9936 6615
Fax 73180 0
Email 73180 0
takecare@mcri.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Privacy and confidentiality/we do not have ethics approval to share individual data
What supporting documents are/will be available?
No other documents available
Summary results
No Results