Post-acute Structured Exercise Following Sport Concussion

Concussion, Brain Clinical Trial

Official title:

Post-acute Structured Exercise Following Sport Concussion: a Randomized Controlled Study

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02969824
• Other study ID #: 33459
• Status: Terminated
• Phase: N/A
• Start date: February 16, 2017
• Est. completion date: September 1, 2020

Study information

• Verified date: December 2021
• Source: University of Toronto
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will investigate the effect of structured, standardized aerobic exercise (AE) compared to usual care on clinical recovery from sport-related concussion (SRC) within the post-acute phase of injury. Participants will be randomized into one of two groups: (1) Supervised Exercise Group: participants will complete a total of eight exercise sessions over the course of 11 days, starting at Day 3 post-injury (two sessions (first and mid-point) will be done in the lab, and the remained will be home-based sessions); (2) Usual Care Group: individuals will undergo a period of physical rest and standard care. For the purposes of this study, "rest" will be defined as the avoidance of any activities beyond those of daily living, including participation in sport and physical activity.

Description:

A number of physical, cognitive, somatic, and emotional symptoms commonly occur following sports-related concussion. The most recent Concussion in Sport Consensus Statement recommends an initial period of rest (24-48 hours), followed by more activity - gradual and progressive - while staying below their cognitive and physical symptom-exacerbation thresholds. While structured exercise is advised post-injury, the appropriate intensity, frequency, and duration of activity remains unclear. Furthermore, there is also evidence that too much physical activity may be related to worse outcomes, which necessitates the investigation on the appropriate prescription of exercise following concussion. Early work identified the potential benefit of exercise in those with persistent symptoms after concussion. However, it is important to recognize that exercise must be structured and tailored as it has been found that athletes engaging in high levels of activity post-injury were associated with greater symptom burden and poorer cognitive abilities. Collectively, these findings further support the potential benefit of personalized, prescribed exercise post-concussion. Additional evidence in support of sub-acute and acute exercise interventions following neurological insult exists for other conditions of the central nervous system, such as low back pain, whiplash, and stroke. For example, research suggests that bed rest may actually delay recovery from acute low back pain, and recommendations to resume regular activities as soon as possible following injury result in faster recovery times, less chronic disability, and fewer recurrent problems. While rest and collar restraint were previously the standard mode of treatment for whiplash, recent evidence suggests that early mobilization and exercise compared to more traditional rest strategies. In terms of stroke, it has been shown that mobilization within 24 hours of this type of injury can expedite recovery while also inducing the risk of complications. Therefore, the purpose of this study is to examine the effect of a structured, standardized, subacute AE intervention in adolescents after SRC, on time to recovery compared to usual care. This study will provide meaningful information regarding the utility of AE intervention after concussion. Findings from these works may inform future usual care procedures post-injury, potentially providing the first known treatment to improve recovery after concussion.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 50
• Est. completion date: September 1, 2020
• Est. primary completion date: July 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 13 Years to 25 Years

Eligibility

Inclusion Criteria:

• Diagnosed with SRC by a physician at the David L. MacIntosh Sport Medicine Clinic
• Minimum of 13 years of age and a maximum of 25 years of age
• Able to speak and understand English

Exclusion Criteria:

• Have had a previous concussion within two weeks of the presenting SRC
• Have any co-morbid injuries (i.e. musculoskeletal/soft-tissue injuries, vestibular disorders)
• Have a pre-existing heart condition
• Have any uncontrolled seizure disorders or a history of medical or neurological conditions that affects cognitive functioning

Related Conditions & MeSH terms

• Brain Concussion
• Concussion, Brain

Intervention

Behavioral:
• Supervised Aerobic Exercise
The AE protocol will consist of eight sessions that proceed in a stepwise fashion in terms of duration and intensity over 11 days. Exercise will be performed on the Velotron Pro stationary cycle ergometer (RacerMate Inc., WA, USA), which will be digitally connected to a heart rate monitor and programmed to monitor the wattage of the bike based on the participant's heart rate. Exercise duration (15min-20min) and intensity (60%-75% max HR) will increase over the intervention period. For the remotely supervised sessions, exercise intensities and heart rate will be monitored via FitBit.

Locations

Country	Name	City	State
Canada	David L. MacIntosh Sport Medicine Clinic	Toronto	Ontario
Canada	Goldring Centre for High Performance Sport	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
University of Toronto

Country where clinical trial is conducted

Canada, 

References & Publications (16)

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. — View Citation

Bernhardt J, Dewey H, Thrift A, Collier J, Donnan G. A very early rehabilitation trial for stroke (AVERT): phase II safety and feasibility. Stroke. 2008 Feb;39(2):390-6. doi: 10.1161/STROKEAHA.107.492363. Epub 2008 Jan 3. — View Citation

Carson JD, Lawrence DW, Kraft SA, Garel A, Snow CL, Chatterjee A, Libfeld P, MacKenzie HM, Thornton JS, Moineddin R, Frémont P. Premature return to play and return to learn after a sport-related concussion: physician's chart review. Can Fam Physician. 2014 Jun;60(6):e310, e312-5. — View Citation

Dahm KT, Brurberg KG, Jamtvedt G, Hagen KB. Advice to rest in bed versus advice to stay active for acute low-back pain and sciatica. Cochrane Database Syst Rev. 2010 Jun 16;(6):CD007612. doi: 10.1002/14651858.CD007612.pub2. Review. — View Citation

Dishman RK, Berthoud HR, Booth FW, Cotman CW, Edgerton VR, Fleshner MR, Gandevia SC, Gomez-Pinilla F, Greenwood BN, Hillman CH, Kramer AF, Levin BE, Moran TH, Russo-Neustadt AA, Salamone JD, Van Hoomissen JD, Wade CE, York DA, Zigmond MJ. Neurobiology of exercise. Obesity (Silver Spring). 2006 Mar;14(3):345-56. Review. — View Citation

Hagen KB, Jamtvedt G, Hilde G, Winnem MF. The updated cochrane review of bed rest for low back pain and sciatica. Spine (Phila Pa 1976). 2005 Mar 1;30(5):542-6. Review. — View Citation

Leddy JJ, Cox JL, Baker JG, Wack DS, Pendergast DR, Zivadinov R, Willer B. Exercise treatment for postconcussion syndrome: a pilot study of changes in functional magnetic resonance imaging activation, physiology, and symptoms. J Head Trauma Rehabil. 2013 Jul-Aug;28(4):241-9. doi: 10.1097/HTR.0b013e31826da964. — View Citation

Marzolini S, Tang A, McIlroy W, Oh PI, Brooks D. Outcomes in people after stroke attending an adapted cardiac rehabilitation exercise program: does time from stroke make a difference? J Stroke Cerebrovasc Dis. 2014 Jul;23(6):1648-56. doi: 10.1016/j.jstrokecerebrovasdis.2014.01.008. Epub 2014 Apr 5. — View Citation

McCrory P, Meeuwisse W, Aubry M, Cantu B, Dvorak J, Echemendia RJ, Engebretsen L, Johnston K, Kutcher JS, Raftery M, Sills A; Kathryn Schneider, PT, PhD, Charles H. Tator, MD, PHD, Benson BW, Davis GA, Ellenbogen RG, Guskiewicz KM, Herring SA, Iverson G, Jordan BD, Kissick J, McCrea M, McIntosh AS, Maddocks DL, Makdissi M, Purcell L, Putukian M, Turner M, Schneider K, Tator CH. Consensus statement on concussion in sport--the 4th International Conference on Concussion in Sport held in Zurich, November 2012. Clin J Sport Med. 2013 Mar;23(2):89-117. doi: 10.1097/JSM.0b013e31828b67cf. — View Citation

McCrory P, Meeuwisse W, Dvorák J, Aubry M, Bailes J, Broglio S, Cantu RC, Cassidy D, Echemendia RJ, Castellani RJ, Davis GA, Ellenbogen R, Emery C, Engebretsen L, Feddermann-Demont N, Giza CC, Guskiewicz KM, Herring S, Iverson GL, Johnston KM, Kissick J, Kutcher J, Leddy JJ, Maddocks D, Makdissi M, Manley GT, McCrea M, Meehan WP, Nagahiro S, Patricios J, Putukian M, Schneider KJ, Sills A, Tator CH, Turner M, Vos PE. Consensus statement on concussion in sport-the 5(th) international conference on concussion in sport held in Berlin, October 2016. Br J Sports Med. 2017 Jun;51(11):838-847. doi: 10.1136/bjsports-2017-097699. Epub 2017 Apr 26. — View Citation

Schnabel M, Ferrari R, Vassiliou T, Kaluza G. Randomised, controlled outcome study of active mobilisation compared with collar therapy for whiplash injury. Emerg Med J. 2004 May;21(3):306-10. — View Citation

Silverberg ND, Iverson GL. Is rest after concussion "the best medicine?": recommendations for activity resumption following concussion in athletes, civilians, and military service members. J Head Trauma Rehabil. 2013 Jul-Aug;28(4):250-9. doi: 10.1097/HTR.0b013e31825ad658. Review. — View Citation

Teasell RW, McClure JA, Walton D, Pretty J, Salter K, Meyer M, Sequeira K, Death B. A research synthesis of therapeutic interventions for whiplash-associated disorder (WAD): part 4 - noninvasive interventions for chronic WAD. Pain Res Manag. 2010 Sep-Oct;15(5):313-22. Review. — View Citation

Thomas DG, Apps JN, Hoffmann RG, McCrea M, Hammeke T. Benefits of strict rest after acute concussion: a randomized controlled trial. Pediatrics. 2015 Feb;135(2):213-23. doi: 10.1542/peds.2014-0966. Epub 2015 Jan 5. — View Citation

Waddell G, Feder G, Lewis M. Systematic reviews of bed rest and advice to stay active for acute low back pain. Br J Gen Pract. 1997 Oct;47(423):647-52. Review. — View Citation

Williams RM, Puetz TW, Giza CC, Broglio SP. Concussion recovery time among high school and collegiate athletes: a systematic review and meta-analysis. Sports Med. 2015 Jun;45(6):893-903. doi: 10.1007/s40279-015-0325-8. Review. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical recovery - Days to Medical Clearance	Number of days from the time of injury until a concussed athlete is cleared to return to play by a sport-medicine physician.	Up to 1-year post-injury
Secondary	Change in Symptoms	Concussion-related symptoms will be assessed using the Post-Concussion Symptom Scale (PCSS) of the Sport Concussion Assessment Tool-3 (SCAT3). The symptom score is comprised of a 22-item post-concussion symptom scale using a seven-point Likert scale rating. Total symptoms is the total number of symptoms with a non-zero score and symptom severity is obtained by summing the rated symptom score for each symptom.	28 Days: assessed at Days 7, 14, 21, 28, and 90 post-injury
Secondary	Change in Heart Rate Variability (HRV)	Heart Rate Variability (HRV) will be assessed using the Polar heart rate V800 sports watch and corresponding chest strap heart monitor (Polar ®, QC, Canada). HRV will be assessed for 5 minutes in the supine position, followed by a 1-minute accommodation period, a final five-minute HRV assessment in the upright-seated position will be performed. HRV measurements to be analyzed HRV was assessed using both time domain and frequency domain measures, in accordance with recommendations of the Task Force of the European Society Cardiology and North American Society of Pacing and Electrophysiology.	28 Days: assessed at Days 7, 14, 21, 28, and 90 post-injury
Secondary	Change in Blood Pressure Variability (BPV)	Blood Pressure Variability (BPV) will be measured using the Finapres MIDI figure cuff device concurrently with HRV. Systolic BP and diastolic BP values will be acquired throughout the acquisition period.	28 days: assessed at Days 7, 14, 21, 28, and 90 post-injury
Secondary	Change in Peripheral Blood Biomarkers	Peripheral blood samples (approximately 20 mL) will be drawn from participants by a trained phlebotomist. High sensitivity multiplexed immunoassay will be employed to quantitate 30 inflammatory cytokines and chemokines, and 11 central nervous-injury specific biomarkers. Individual biomarker values will be excluded if they were above or below the manufacturers' recommended level of quantitation for each analyte, or displayed a coefficient of variance >25% between duplicates. Because multiple 96-well plates will analyzed, inter-plate variance will also be accounted for; therefore, plates will only be included in the statistical analysis if the inter-plate variance was <20%, calculated from internal control samples acquired on each plate. Raw values of biomarker analyte will be used in all analyses.	28 Days: assessed at Days 7, 14, 21, 28, and 90 post-injury
Secondary	Change in Cognition	C3 Logix (iPad platform, Cleveland, OH, USA), will be employed to measure reaction time, information processing speed, visual acuity, and postural stability. This assessment will take approximately 10-15 minutes to complete. For each of subtest, the percent correct (accuracy) and reaction time (ms) will be analyzed.	28 Days: assessed at Days 7, 14, 21, 28, and 90 post-injury
Secondary	Salivary MicroRNA and DNA Collection	A research team member will collect a very small amount of saliva (approximately 1mL) using a swab for MicroRNA analysis, and 2ml of liquid saliva for DNA analysis. This process normally takes approximately 3 minutes.	28 Days: assessed at Days 7, 14, 21, 28, and 90 post-injury