Clinical trial NCT02959216: Aerobic Exercise for Concussion
Official title: Sub-Symptom Aerobic Exercise Therapy to Improve Recovery From Acute Sport-Related Concussion: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Mild Traumatic Brain Injury
Acute Brain Injury
Brain Concussion
Keywords: Aerobic Exercise
Lead sponsor: Children's Hospital of Philadelphia
Sponsor class: OTHER
Collaborators: name: University at Buffalo
name: Boston Children's Hospital
First posted: 2016-11-09
Enrollment: 125
Sex: ALL
Minimum age (years): 13
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The use of aerobic exercise treatment in the chronic phase of concussion recovery is well-described in the literature but there are limited existing data on the effect of exercise treatment in the acute phase after sport-related concussion (SRC). This study will compare the outcomes of adolescents with a recent SRC who are randomized to sub-threshold aerobic exercise versus those randomized to placebo stretching to evaluate the effect of aerobic exercise in the acute recovery phase.

Detailed description: Historically, concussion has been described as a cognitive injury and patients have been advised not to engage in any cognitive or physical exertion while symptomatic. More recently, however, concussion has been described as a physiological injury affecting both the heart and autonomic nervous system, and patients suffering from prolonged concussion-related symptoms and deficits have been encouraged to begin aerobic exercise as part of their concussion care. While intensive exercise too soon after concussion has been associated with delayed recovery and used to justify prolonged periods of rest, recent studies have shown that controlled, sub-symptom threshold aerobic exercise may aid recovery by improving autonomic balance and cerebral blood flow auto-regulation after concussion. This study will randomly assign pediatric patients with concussion to a treatment group in which they will complete sub-symptom threshold aerobic exercise or to a placebo group in which they will complete a standardized stretching protocol. All participants will have routine visits that consist of a physical examination and exercise test until the intervention ends at recovery or 1-month post-randomization.

Eligibility criteria: Inclusion Criteria (Case Subjects):

* Sports-related concussion (organized or recreational).
* Physician-diagnosed concussion within the last 10 days.
* Symptom score difference ≥3 on the Post-Concussion Symptom Inventory (PCSI) Current versus PCSI Pre-Injury.
* Parental/guardian permission (informed consent) and child assent.

Inclusion Criteria (Control Subjects):

* No known recent concussion within the past year or still causing active symptoms.
* Parental/guardian permission (informed consent) and child assent.

Exclusion Criteria (Case and Control Subjects):

* Subjects with moderate or severe traumatic brain injury as indicated by a score \<13 on Glasgow Coma Scale (GCS), presence of lesion on CT/MRI, and/or focal neurologic deficit consistent with an intracerebral lesion.
* History of more than 3 diagnosed concussions.
* Subjects that sustained an injury involving loss of consciousness for 30+ minutes or post-traumatic amnesia for 24+ hours.
* Inability to exercise because of lower-extremity orthopedic injury, significant vestibular or visual dysfunction, or increased cardiac risk.
* Pre-existing comorbidities, such as chronic pain, cardiac, neurological, or autoimmune conditions, that prevent participation in active testing and/or rehabilitation.
* Currently taking medications that can affect autonomic function.
* Active substance abuse/dependence.
* Unwillingness to exercise or unable to access place to safely exercise.
* Parental/guardian permission (informed consent) not obtainable or not provided
* Cannot understand English.

Exclusion Criteria (Case Subjects Only):

* Additional head injury during the intervention.
* Parents/ guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.

Primary outcomes:
measure: Time to recovery
timeFrame: 3 to 28 days
Secondary outcomes:
measure: Persistence of post-concussive symptoms
timeFrame: 29 to 112 days
Other outcomes:
Locations:
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Buffalo
country: United States
facility: University at Buffalo
state: New York
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: University at Buffalo
name: John Leddy, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital of Philadelphia
name: Christina Master, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Boston Children's Hospital
name: Rebekah Mannix, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Leddy JJ, Willer B. Use of graded exercise testing in concussion and return-to-activity management. Curr Sports Med Rep. 2013 Nov-Dec;12(6):370-6. doi: 10.1249/JSR.0000000000000008.
citation: Leddy J, Hinds A, Sirica D, Willer B. The Role of Controlled Exercise in Concussion Management. PM R. 2016 Mar;8(3 Suppl):S91-S100. doi: 10.1016/j.pmrj.2015.10.017.
citation: Leddy JJ, Kozlowski K, Donnelly JP, Pendergast DR, Epstein LH, Willer B. A preliminary study of subsymptom threshold exercise training for refractory post-concussion syndrome. Clin J Sport Med. 2010 Jan;20(1):21-7. doi: 10.1097/JSM.0b013e3181c6c22c.
citation: Leddy JJ, Hinds AL, Miecznikowski J, Darling S, Matuszak J, Baker JG, Picano J, Willer B. Safety and Prognostic Utility of Provocative Exercise Testing in Acutely Concussed Adolescents: A Randomized Trial. Clin J Sport Med. 2018 Jan;28(1):13-20. doi: 10.1097/JSM.0000000000000431.
citation: Chizuk HM, Willer BS, Cunningham A, Bezherano I, Storey E, Master C, Mannix R, Wiebe DJ, Grady MF, Meehan WP, Leddy JJ, Haider MN. Adolescents with Sport-Related Concussion Who Adhere to Aerobic Exercise Prescriptions Recover Faster. Med Sci Sports Exerc. 2022 Sep 1;54(9):1410-1416. doi: 10.1249/MSS.0000000000002952. Epub 2022 Apr 28.
citation: Leddy JJ, Master CL, Mannix R, Wiebe DJ, Grady MF, Meehan WP, Storey EP, Vernau BT, Brown NJ, Hunt D, Mohammed F, Mallon A, Rownd K, Arbogast KB, Cunningham A, Haider MN, Mayer AR, Willer BS. Early targeted heart rate aerobic exercise versus placebo stretching for sport-related concussion in adolescents: a randomised controlled trial. Lancet Child Adolesc Health. 2021 Nov;5(11):792-799. doi: 10.1016/S2352-4642(21)00267-4. Epub 2021 Oct 1.