Treating Persistent Post-concussion Symptoms With Exercise

NCT03895450 | Completed DMC

• 1 other identifier: REB18-1329
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

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

Outcome Measures

Primary Outcomes (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.

  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)

• Change in sleep duration

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

• Change in daytime sleepiness

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

• Change in blood derived neurotrophic factor (BDNF)

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

• Change in cytokine profile

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

• Change in telomere length (TL)

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

Study Arms (2)

Aerobic Exercise Protocol (AEP)

EXPERIMENTAL

Symptom 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.

Behavioral: Aerobic Exercise Protocol

Stretching Protocol (SP)

PLACEBO COMPARATOR

The exercise testing for the stretching protocol to determine exercise prescription will be the same as described above.

Behavioral: Aerobic Exercise Protocol; Behavioral: Stretching Protocol

Interventions

Aerobic Exercise Protocol BEHAVIORAL

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.

Aerobic Exercise Protocol (AEP); Stretching Protocol (SP)

Stretching Protocol BEHAVIORAL

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.

Stretching Protocol (SP)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Calgary: lead
• Hotchkiss Brain Institute, University of Calgary: collaborator

Study Sites (1)

University Of Calgary

Calgary, Alberta, T2N 4Z6, Canada

Location

Related Publications (41)

• 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.

  PMID: 26360006 BACKGROUND

• 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.

  PMID: 15083870 BACKGROUND

• 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.

  PMID: 26289372 BACKGROUND

• 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.

  PMID: 12940825 BACKGROUND

• 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.

  PMID: 23836998 BACKGROUND

• 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.

  PMID: 24723461 BACKGROUND

• 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.

  PMID: 24263178 BACKGROUND

• 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.

  PMID: 20631632 BACKGROUND

• 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.

  PMID: 27521273 BACKGROUND

• 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.

  PMID: 28503402 BACKGROUND

• 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.

  PMID: 18609015 BACKGROUND

• 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.

  PMID: 28436583 BACKGROUND

• 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.

  PMID: 28444695 BACKGROUND

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

  PMID: 23648606 BACKGROUND

• 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.

  PMID: 24260348 BACKGROUND

• Piao CS, Stoica BA, Wu J, Sabirzhanov B, Zhao Z, Cabatbat R, Loane DJ, Faden AI. Late exercise reduces neuroinflammation and cognitive dysfunction after traumatic brain injury. Neurobiol Dis. 2013 Jun;54:252-63. doi: 10.1016/j.nbd.2012.12.017. Epub 2013 Jan 8.

  PMID: 23313314 BACKGROUND

• Molteni R, Zheng JQ, Ying Z, Gomez-Pinilla F, Twiss JL. Voluntary exercise increases axonal regeneration from sensory neurons. Proc Natl Acad Sci U S A. 2004 Jun 1;101(22):8473-8. doi: 10.1073/pnas.0401443101. Epub 2004 May 24.

  PMID: 15159540 BACKGROUND

• Cotman CW, Berchtold NC, Christie LA. Exercise builds brain health: key roles of growth factor cascades and inflammation. Trends Neurosci. 2007 Sep;30(9):464-72. doi: 10.1016/j.tins.2007.06.011. Epub 2007 Aug 31.

  PMID: 17765329 BACKGROUND

• Griesbach GS, Hovda DA, Gomez-Pinilla F. Exercise-induced improvement in cognitive performance after traumatic brain injury in rats is dependent on BDNF activation. Brain Res. 2009 Sep 8;1288:105-15. doi: 10.1016/j.brainres.2009.06.045. Epub 2009 Jun 23.

  PMID: 19555673 BACKGROUND

• Fogelman D, Zafonte R. Exercise to enhance neurocognitive function after traumatic brain injury. PM R. 2012 Nov;4(11):908-13. doi: 10.1016/j.pmrj.2012.09.028.

  PMID: 23174558 BACKGROUND

• Wogensen E, Mala H, Mogensen J. The Effects of Exercise on Cognitive Recovery after Acquired Brain Injury in Animal Models: A Systematic Review. Neural Plast. 2015;2015:830871. doi: 10.1155/2015/830871. Epub 2015 Oct 5.

  PMID: 26509085 BACKGROUND

• Martinsen S, Flodin P, Berrebi J, Lofgren M, Bileviciute-Ljungar I, Mannerkorpi K, Ingvar M, Fransson P, Kosek E. The role of long-term physical exercise on performance and brain activation during the Stroop colour word task in fibromyalgia patients. Clin Physiol Funct Imaging. 2018 May;38(3):508-516. doi: 10.1111/cpf.12449. Epub 2017 Jun 18.

  PMID: 28627125 BACKGROUND

• Edwards T, Pilutti LA. The effect of exercise training in adults with multiple sclerosis with severe mobility disability: A systematic review and future research directions. Mult Scler Relat Disord. 2017 Aug;16:31-39. doi: 10.1016/j.msard.2017.06.003. Epub 2017 Jun 12.

  PMID: 28755682 BACKGROUND

• Clark PJ, Brzezinska WJ, Thomas MW, Ryzhenko NA, Toshkov SA, Rhodes JS. Intact neurogenesis is required for benefits of exercise on spatial memory but not motor performance or contextual fear conditioning in C57BL/6J mice. Neuroscience. 2008 Sep 9;155(4):1048-58. doi: 10.1016/j.neuroscience.2008.06.051. Epub 2008 Jul 1.

  PMID: 18664375 BACKGROUND

• Erickson KI, Voss MW, Prakash RS, Basak C, Szabo A, Chaddock L, Kim JS, Heo S, Alves H, White SM, Wojcicki TR, Mailey E, Vieira VJ, Martin SA, Pence BD, Woods JA, McAuley E, Kramer AF. Exercise training increases size of hippocampus and improves memory. Proc Natl Acad Sci U S A. 2011 Feb 15;108(7):3017-22. doi: 10.1073/pnas.1015950108. Epub 2011 Jan 31.

  PMID: 21282661 BACKGROUND

• Biedermann SV, Fuss J, Steinle J, Auer MK, Dormann C, Falfan-Melgoza C, Ende G, Gass P, Weber-Fahr W. The hippocampus and exercise: histological correlates of MR-detected volume changes. Brain Struct Funct. 2016 Apr;221(3):1353-63. doi: 10.1007/s00429-014-0976-5. Epub 2014 Dec 31.

  PMID: 25550000 BACKGROUND

• Chaddock L, Erickson KI, Prakash RS, Kim JS, Voss MW, Vanpatter M, Pontifex MB, Raine LB, Konkel A, Hillman CH, Cohen NJ, Kramer AF. A neuroimaging investigation of the association between aerobic fitness, hippocampal volume, and memory performance in preadolescent children. Brain Res. 2010 Oct 28;1358:172-83. doi: 10.1016/j.brainres.2010.08.049. Epub 2010 Aug 22.

  PMID: 20735996 BACKGROUND

• Hehar H, Mychasiuk R. The use of telomere length as a predictive biomarker for injury prognosis in juvenile rats following a concussion/mild traumatic brain injury. Neurobiol Dis. 2016 Mar;87:11-8. doi: 10.1016/j.nbd.2015.12.007. Epub 2015 Dec 17.

  PMID: 26709201 BACKGROUND

• Leddy J, Baker JG, Haider MN, Hinds A, Willer B. A Physiological Approach to Prolonged Recovery From Sport-Related Concussion. J Athl Train. 2017 Mar;52(3):299-308. doi: 10.4085/1062-6050-51.11.08.

  PMID: 28387557 BACKGROUND

• Leckie RL, Oberlin LE, Voss MW, Prakash RS, Szabo-Reed A, Chaddock-Heyman L, Phillips SM, Gothe NP, Mailey E, Vieira-Potter VJ, Martin SA, Pence BD, Lin M, Parasuraman R, Greenwood PM, Fryxell KJ, Woods JA, McAuley E, Kramer AF, Erickson KI. BDNF mediates improvements in executive function following a 1-year exercise intervention. Front Hum Neurosci. 2014 Dec 11;8:985. doi: 10.3389/fnhum.2014.00985. eCollection 2014.

  PMID: 25566019 BACKGROUND

• Merritt VC, Arnett PA. Apolipoprotein E (APOE) ϵ4 Allele Is Associated with Increased Symptom Reporting Following Sports Concussion. J Int Neuropsychol Soc. 2016 Jan;22(1):89-94. doi: 10.1017/S1355617715001022. Epub 2015 Oct 20.

  PMID: 26483005 BACKGROUND

• Merritt VC, Rabinowitz AR, Arnett PA. The Influence of the Apolipoprotein E (APOE) Gene on Subacute Post-Concussion Neurocognitive Performance in College Athletes. Arch Clin Neuropsychol. 2018 Feb 1;33(1):36-46. doi: 10.1093/arclin/acx051.

  PMID: 28541413 BACKGROUND

• von Steinbuechel N, Covic A, Polinder S, Kohlmann T, Cepulyte U, Poinstingl H, Backhaus J, Bakx W, Bullinger M, Christensen AL, Formisano R, Gibbons H, Hofer S, Koskinen S, Maas A, Neugebauer E, Powell J, Sarajuuri J, Sasse N, Schmidt S, Muhlan H, von Wild K, Zitnay G, Truelle JL. Assessment of Health-Related Quality of Life after TBI: Comparison of a Disease-Specific (QOLIBRI) with a Generic (SF-36) Instrument. Behav Neurol. 2016;2016:7928014. doi: 10.1155/2016/7928014. Epub 2016 Feb 1.

  PMID: 27022207 BACKGROUND

• Esselman PC, Uomoto JM. Classification of the spectrum of mild traumatic brain injury. Brain Inj. 1995 May-Jun;9(4):417-24. doi: 10.3109/02699059509005782.

  PMID: 7640688 BACKGROUND

• Ades PA, Grunvald MH. Cardiopulmonary exercise testing before and after conditioning in older coronary patients. Am Heart J. 1990 Sep;120(3):585-9. doi: 10.1016/0002-8703(90)90015-p.

  PMID: 2389695 BACKGROUND

• Baker JG, Freitas MS, Leddy JJ, Kozlowski KF, Willer BS. Return to full functioning after graded exercise assessment and progressive exercise treatment of postconcussion syndrome. Rehabil Res Pract. 2012;2012:705309. doi: 10.1155/2012/705309. Epub 2012 Jan 16.

  PMID: 22292122 BACKGROUND

• Leddy JJ, Sandhu H, Sodhi V, Baker JG, Willer B. Rehabilitation of Concussion and Post-concussion Syndrome. Sports Health. 2012 Mar;4(2):147-54. doi: 10.1177/1941738111433673.

  PMID: 23016082 BACKGROUND

• Polak P, Leddy JJ, Dwyer MG, Willer B, Zivadinov R. Diffusion tensor imaging alterations in patients with postconcussion syndrome undergoing exercise treatment: a pilot longitudinal study. J Head Trauma Rehabil. 2015 Mar-Apr;30(2):E32-42. doi: 10.1097/HTR.0000000000000037.

  PMID: 24721808 BACKGROUND

• Donnelly KZ, Linnea K, Grant DA, Lichtenstein J. The feasibility and impact of a yoga pilot programme on the quality-of-life of adults with acquired brain injury. Brain Inj. 2017;31(2):208-214. doi: 10.1080/02699052.2016.1225988. Epub 2016 Dec 12.

  PMID: 27936953 BACKGROUND

• Mercier LJ, McIntosh SJ, Boucher C, Joyce JM, Batycky J, Galarneau JM, Esser MJ, Schneider KJ, Dukelow SP, Harris AD, Debert CT. Effect of Aerobic Exercise on Symptom Burden and Quality of Life in Adults With Persisting Post-concussive Symptoms: The ACTBI Randomized Controlled Trial. Arch Phys Med Rehabil. 2025 Feb;106(2):195-205. doi: 10.1016/j.apmr.2024.10.002. Epub 2024 Oct 18.

  PMID: 39427780 DERIVED

• Mercier LJ, Fung TS, Harris AD, Dukelow SP, Debert CT. Improving symptom burden in adults with persistent post-concussive symptoms: a randomized aerobic exercise trial protocol. BMC Neurol. 2020 Feb 5;20(1):46. doi: 10.1186/s12883-020-1622-x.

  PMID: 32024486 DERIVED

MeSH Terms

Conditions

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

Condition Hierarchy (Ancestors)

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

Study Officials

• Chantel T Debert, MD MSc FRCPC

  University of Calgary

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: Allocation will be concealed through the use of sequentially numbered, opaque envelopes.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2019
• First Posted: March 29, 2019
• Study Start: May 24, 2019
• Primary Completion: February 20, 2023
• Study Completion: February 20, 2023
• Last Updated: October 23, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)