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Brain Injuries, TraumaticNCT03895450

Treating Persistent Post-concussion Symptoms With Exercise

A study testing Aerobic Exercise Protocol and Stretching Protocol in people with Brain Injuries, Traumatic and Concussion, Brain, run by University of Calgary at 1 site in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The objective of this study is to investigate an aerobic exercise program as a treatment for adults with persistent post-concussive symptoms (PPCS) following mild traumatic brain injury. Read more about this study

Who is it for?
Ages 18 to 65 years
What is being tested?
Aerobic Exercise Protocol and Stretching Protocol
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
52 participants
Where
1 siteCanada
Study dates
24 May 2019to 20 Feb 2023
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diagnosis of mild traumatic brain injury (mTBI) based on the American Congress of Rehabilitation Medicine (ACRM) criteria.
  • mTBI occurrence from 3 months to 5 years from study start date
  • Diagnosis of persistent post-concussion symptoms based on the ICD-10 criteria.
  • Cleared for physical activity based on The Physical Activity Readiness Questionnaire for Everyone (PAR-Q+) by treating physician
  • exercise intolerance (inability to exercise at pre-injury intensity/duration due to acute presentation of symptoms)

Who cannot join

  • past medical history of neurological disorders (i.e., Parkinson's disease, neuromuscular disorders)
  • contraindications to MRI
  • cardiopulmonary disorder
  • chronic musculoskeletal condition
  • psychiatric disorder other than depression and/or anxiety (i.e., schizophrenia, bipolar disorder)
  • cancer
  • pregnancy

Trial locations and contacts

1 site in 1 country.

Canada1 site

  • University Of Calgary

    Calgary, Alberta, T2N 4Z6

Other trials in Canada

About this study

Official title: Improving Symptom Burden in Individuals With Persistent Post Concussive Symptoms: A Step-wise Aerobic Exercise Trial

The objective of this study is to investigate an aerobic exercise program as a treatment for adults with persistent post-concussive symptoms (PPCS) following mild traumatic brain injury. In this delayed-start trial participants will be initially randomized into either a 6-week low-impact stretching protocol or 12-week aerobic exercise protocol. Following the completion of the stretching protocol participants will continue on to complete the aerobic exercise protocol in full. 56 participants aged 18-65 yrs will be recruited from the Calgary Brain Injury Program (CBIP), including the Early Concussion Education Program at Foothills Medical Centre, Calgary Pain Program, University of Calgary Sports Medicine Centre acute concussion clinic and a physiotherapy clinic (Tower Physio) all of which are located in Calgary, Alberta, Canada. Participants will complete an online follow up (symptom questionnaires and questions regarding exercise behaviour) 3 and 9 weeks post intervention.

Read the detailed description

Demographic information will be collected prior to study participation and include age, sex, education, family medical history, past medical history, concussion history, litigious status and medication use. The PAR-Q+ questionnaire will be completed to determine readiness for exercise by a physician. Baseline questionnaires will be completed, such as the Fatigue Severity Scale (FSS), Generalized Anxiety Disorder Scale (GAD-7), Headache Intensity Scale-6 (HIT-6), Patient Health Questionnaire(PHQ-9), Epworth Sleepiness Scale(ESS) and Quality of Life After Brain Injury(QOLIBRI), Rivermead Post Concussion Symptoms Questionnaire (RPQ), Modified Godin Leisure-Time Exercise Questionnaire(GLTQ), Rapid Assessment Disuse Index (RADI) and Postconcusion Syndrome Checklist (PCSC). Pre- and post-intervention blood samples will be collected from all participants. Participants will be asked to perform a tactile assessment pre- and post-intervention. Sleep will be monitored using wrist-based actigraphy and a sleep diary for 3-6 days/nights prior to the intervention start and for five days following completion of the exercise protocol. Pre and post magnetic resonance spectroscopy (MRS) will also be completed. Participants will be randomized to a structured aerobic exercise protocol (AEP) or stretching protocol, followed by aerobic exercise protocol(SP+AEP) with a random number generator. Both groups will undergo exercise testing using the Buffalo Concussion Treadmill Test to determine exercise prescription. Upon completion of SP, participants will continue on to the AEP and complete it in full. Following the exercise protocols, all questionnaires will be completed post-intervention. At 3 and 9 weeks following protocol completion, online follow surveys will be completed to assess symptom burden (RPQ, QOLIBRI, HIT-6, ESS, FSS) along with questions regarding current exercise.

Being tested
Aerobic Exercise Protocol, Stretching Protocol
Medical subject headings
Brain Injuries, Traumatic, Brain Concussion, Post-Concussion Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Aerobic Exercise ProtocolBehavioural

    Participants randomized to AEP will be asked to exercise 30 minutes per day or until symptom exacerbation, 5 days per week either at home, outdoors or at a fitness facility of choice. The assigned exercise prescription target will be 70-80% of the maximum HR achieved during the treadmill test. HR monitors will be provided to monitor exercise intensity.

  • Stretching ProtocolBehavioural

    Participants will follow a stretching protocol for 30 minutes a day, 5 days a week. Individuals in the SP group will be given a booklet explaining a low-impact breathing and stretching program developed at the University of Buffalo. All stretches will explained and demonstrated by a member of the study team prior to commencement of the program. Stretches focus on lower extremity muscles. During the protocol HR should be low as to not exceed 50% of age predicted max. A HR monitor will be worn during stretching.

Study groups in NCT03895450
Study groupRoleWhat they receive
Aerobic Exercise Protocol (AEP)ExperimentalSymptom threshold will be determined at baseline and repeated every 3 weeks using the Buffalo Concussion Treadmill Test. Briefly, there will be an initial 4min warm up at 1.7mph. The protocol will start with treadmill speed se to 3.3 mph and 0.0% incline. Each subsequent minute, the incline will increase by 1.0% to a max of 15%. At 15% grade, if the participant is still able to continue, treadmill speed will increase by 0.4mph each minute. Heart rate (HR) and rating of perceived excretion (RPE Borg scale) will be measured every minute. The test will be terminated upon symptom exacerbation at which time HR and RPE will be recorded. Every 3 weeks the symptom threshold test will be repeated for all participants and exercise prescription will be adjusted accordingly.
Receives: Behavioral: Aerobic Exercise Protocol
Stretching Protocol (SP)Placebo comparatorThe exercise testing for the stretching protocol to determine exercise prescription will be the same as described above.
Receives: Behavioral: Aerobic Exercise Protocol; Behavioral: Stretching Protocol

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in symptom burden

    Rivermead Post-concussion Symptoms Questionnaire (RPQ): an instrument developed to assess the frequency and severity of 16 common post-concussion symptoms. On this paper and pencil tool, patients rate the extent to which their symptoms (compared to their pre-injury levels) have become more problematic over the past 24 hours using a rating scale from 0-4 (0=not experienced, 1=no more of a problem, 2=mild problem, 3=moderate problem, 4=severe problem). A total symptom score is calculated out of 64.

    Measured: Repeated measure: Pre-intervention, after 6-weeks of SP/AEP, after 12-weeks of AEP, 3-weeks post-AEP, 9-weeks post-AEP

Secondary outcomes (10)

  1. Change in sleep duration

    Wrist actigraphy confirmed by a sleep diary. An actigraph (MotionWatch8 [CamNTech]) watch will be worn on the non-dominant wrist during nighttime hours. Actigraphy results will be confirmed by a sleep diary completed in the morning.

    Measured: Repeated measure: Pre-intervention, after 6-weeks of SP/AEP, after 12-weeks of AEP

  2. Change in daytime sleepiness

    Epworth Sleepiness Scale (ESS): measure of daytime sleepiness. This scale rates the chance of dozing off on a scale of 0-3 (0= would never doze, 1= slight chance of dozing, 2= moderate chance of dozing, 3=high chance of dozing) in 8 different situations.

    Measured: Repeated measure: Pre-intervention, after 6-weeks of SP/AEP, after 12-weeks of AEP, 3-weeks post-AEP, 9-weeks post-AEP

  3. Change in blood derived neurotrophic factor (BDNF)

    BDNF: serum BDNF, a neurotropic factor involved in neuronal repair after injury, will be analyzed for change in serum concentration

    Measured: Repeated measure: Pre-intervention, after 6-weeks of SP/AEP, after 12-weeks of AEP

  4. Change in cytokine profile

    Cytokine profile: serum levels of multiple cytokines will be used to characterise chronic inflammatory changes

    Measured: Repeated measure: Pre-intervention, after 6-weeks of SP/AEP, after 12-weeks of AEP

  5. Change in telomere length (TL)

    Telomeres are non-coding sequences of DNA that are found at the end of linear eukaryotic chromosomes thought to play a role in DNA strand repair. TL length will be analyzed using whole blood collected across time points.

    Measured: Repeated measure: Pre-intervention, after 6-weeks of SP/AEP, after 12-weeks of AEP

  6. Change in fatigue

    Fatigue Severity Scale (FSS): 9 instrument questionnaire. Each item is rated on a 7 point likert scale (1= Strongly disagree, 7=strongly agree). Total score is calculated by adding the score from each item producing a total out of 63. A final item asks to "Please mark "X" on a number line which describes your global fatigue with 0 being worst and 10 being normal."

    Measured: Repeated measure: Pre-intervention, after 6-weeks of SP/AEP, after 12-weeks of AEP, 3-weeks post-AEP, 9-weeks post-AEP

  7. Change in anxiety

    Generalized Anxiety Disorder (GAD-7): a 7-item tool where each item is rated on frequency over a 2 week period based on a 0-3 scale (0=not at all, 1=several days, 2=more than half the days, 3=nearly every day). The total score ranges from 0 to 21, with scores indicating severity of anxiety (ie. 0-5= mild, 6-10= moderate, 11-15= moderately severe, 16-21= very severe).

    Measured: Repeated measure: Pre-intervention, after 6-weeks of SP/AEP, after 12-weeks of AEP

  8. Change in function related to headaches

    Headache Impact Test (HIT-6): a global measure of headache impact. Addresses the 6 categories of headache impact including social, ADL, and cognitive functioning, vitality, psychological distress, and severity of headache pain. Each question is scored on a 5 point scale (never, rarely, sometimes, very often, always). Total score can range from 36-78, with higher total score indicating greater impact.

    Measured: Repeated measure: Pre-intervention, after 6-weeks of SP/AEP, after 12-weeks of AEP, 3-weeks post-AEP, 9-weeks post-AEP

  9. Change in depression

    Patient Health Questionnaire-9 (PHQ-9): 9 item tool to assess the presence and severity of depressive symptoms. Each item is rated based on the frequency of occurrence in the past 2 weeks and is graded ona 0-3 scale (0=not at all, 1=several days, 2= more than half of the days, 3= nearly every day). A stand-alone question asks to rate how difficult problems have made completing tasks at home, doing work, and getting along with people. This is graded on a 4-point scale from not difficult at all to extremely difficult. Total score is calculated out of 27, with the value indicating severity of depression (ie. 0-4= none to mild, 5-9= mild, 10-14= moderate, 15-19= moderately severe, and 20-27= very severe).

    Measured: Repeated measure: Pre-intervention, after 6-weeks of SP/AEP, after 12-weeks of AEP

  10. MRS quantification of GABA/Glutathione

    Changes in GABA, glutathione and glutamate in the dorsolateral perefrontal cortex between AEP and SP group at 6 months

    Measured: Repeated measure: Pre-intervention, after 6-weeks of SP/AEP, after 12-week of AEP

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Mar 2019
  2. Study start24 May 2019
  3. Primary completion20 Feb 2023
  4. Study completion20 Feb 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
Single blind
Who is masked
Investigator
Enrolment
52 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03895450
Sponsor's protocol ID
REB18-1329
Status last verified
Oct 2023
First submitted
11 Feb 2019
Last updated
23 Oct 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Korley FK, Kelen GD, Jones CM, Diaz-Arrastia R. Emergency Department Evaluation of Traumatic Brain Injury in the United States, 2009-2010. J Head Trauma Rehabil. 2016 Nov/Dec;31(6):379-387. doi: 10.1097/HTR.0000000000000187.

    PubMed 26360006

  • Cassidy JD, Carroll LJ, Peloso PM, Borg J, von Holst H, Holm L, Kraus J, Coronado VG; WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury. Incidence, risk factors and prevention of mild traumatic brain injury: results of the WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury. J Rehabil Med. 2004 Feb;(43 Suppl):28-60. doi: 10.1080/16501960410023732.

    PubMed 15083870

  • Coenen M, Cabello M, Umlauf S, Ayuso-Mateos JL, Anczewska M, Tourunen J, Leonardi M, Cieza A; PARADISE Consortium. Psychosocial difficulties from the perspective of persons with neuropsychiatric disorders. Disabil Rehabil. 2016;38(12):1134-45. doi: 10.3109/09638288.2015.1074729. Epub 2015 Aug 18.

    PubMed 26289372

  • Olesen J, Leonardi M. The burden of brain diseases in Europe. Eur J Neurol. 2003 Sep;10(5):471-7. doi: 10.1046/j.1468-1331.2003.00682.x.

    PubMed 12940825

  • Humphreys I, Wood RL, Phillips CJ, Macey S. The costs of traumatic brain injury: a literature review. Clinicoecon Outcomes Res. 2013 Jun 26;5:281-7. doi: 10.2147/CEOR.S44625. Print 2013.

    PubMed 23836998

  • Lange RT, Brickell TA, Kennedy JE, Bailie JM, Sills C, Asmussen S, Amador R, Dilay A, Ivins B, French LM. Factors influencing postconcussion and posttraumatic stress symptom reporting following military-related concurrent polytrauma and traumatic brain injury. Arch Clin Neuropsychol. 2014 Jun;29(4):329-47. doi: 10.1093/arclin/acu013. Epub 2014 Apr 9.

    PubMed 24723461

  • Waljas M, Iverson GL, Lange RT, Liimatainen S, Hartikainen KM, Dastidar P, Soimakallio S, Ohman J. Return to work following mild traumatic brain injury. J Head Trauma Rehabil. 2014 Sep-Oct;29(5):443-50. doi: 10.1097/HTR.0000000000000002.

    PubMed 24263178

  • Lange RT, Iverson GL, Rose A. Depression strongly influences postconcussion symptom reporting following mild traumatic brain injury. J Head Trauma Rehabil. 2011 Mar-Apr;26(2):127-37. doi: 10.1097/HTR.0b013e3181e4622a.

    PubMed 20631632

  • Mychasiuk R, Hehar H, Ma I, Candy S, Esser MJ. Reducing the time interval between concussion and voluntary exercise restores motor impairment, short-term memory, and alterations to gene expression. Eur J Neurosci. 2016 Oct;44(7):2407-2417. doi: 10.1111/ejn.13360. Epub 2016 Aug 31.

    PubMed 27521273

  • Hearing CM, Chang WC, Szuhany KL, Deckersbach T, Nierenberg AA, Sylvia LG. Physical Exercise for Treatment of Mood Disorders: A Critical Review. Curr Behav Neurosci Rep. 2016 Dec;3(4):350-359. doi: 10.1007/s40473-016-0089-y. Epub 2016 Oct 14.

    PubMed 28503402

  • Stroth S, Hille K, Spitzer M, Reinhardt R. Aerobic endurance exercise benefits memory and affect in young adults. Neuropsychol Rehabil. 2009 Apr;19(2):223-43. doi: 10.1080/09602010802091183. Epub 2008 Jun 1.

    PubMed 18609015

  • Geneen LJ, Moore RA, Clarke C, Martin D, Colvin LA, Smith BH. Physical activity and exercise for chronic pain in adults: an overview of Cochrane Reviews. Cochrane Database Syst Rev. 2017 Apr 24;4(4):CD011279. doi: 10.1002/14651858.CD011279.pub3.

    PubMed 28436583

  • Larun L, Brurberg KG, Odgaard-Jensen J, Price JR. Exercise therapy for chronic fatigue syndrome. Cochrane Database Syst Rev. 2017 Apr 25;4(4):CD003200. doi: 10.1002/14651858.CD003200.pub7.

    PubMed 28444695

  • Gurley JM, Hujsak BD, Kelly JL. Vestibular rehabilitation following mild traumatic brain injury. NeuroRehabilitation. 2013;32(3):519-28. doi: 10.3233/NRE-130874.

    PubMed 23648606

  • Zhang QW, Deng XX, Sun X, Xu JX, Sun FY. Exercise promotes axon regeneration of newborn striatonigral and corticonigral projection neurons in rats after ischemic stroke. PLoS One. 2013 Nov 19;8(11):e80139. doi: 10.1371/journal.pone.0080139. eCollection 2013.

    PubMed 24260348

Questions about this trial

What is this clinical trial studying?

A study testing Aerobic Exercise Protocol and Stretching Protocol in people with Brain Injuries, Traumatic and Concussion, Brain, run by University of Calgary at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in symptom burden (time frame: Repeated measure: Pre-intervention, after 6-weeks of SP/AEP, after 12-weeks of AEP, 3-weeks post-AEP, 9-weeks post-AEP). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03895450, which also lists 41 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Oct 2023.

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