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Early Sub-threshold Exercise Treatment for Concussion

Not Applicable
Withdrawn
Conditions
Concussion, Mild
Interventions
Behavioral: Stretching
Behavioral: Rest
Behavioral: Aerobic Exercise
Registration Number
NCT03569709
Lead Sponsor
State University of New York at Buffalo
Brief Summary

Each year millions of Americans suffer concussions as a result of accidents in sports, at work or through military service. Adolescents take the longest to recover from the effects of concussion yet no therapy exists to help speed their recovery. This project aims to see if a program of early guided aerobic exercise can safely speed recovery from concussion in adolescents and investigates some reasons for why this type of therapy could be effective.

Detailed Description

Most children with concussion recover spontaneously within 2-4 weeks of injury but approximately 30% experience prolonged post-concussive symptoms (PPCS), impacting quality of life. There are no evidence-based therapies for acute pediatric concussion. Instead, current consensus-based-recommendations include physical and cognitive rest as the mainstays of treatment despite evidence to the contrary that excessive rest prolongs recovery and that early (first week) activity reduces PPCS incidence. The investigators were the first to demonstrate that a systematic evaluation of exercise tolerance using the Buffalo Concussion Treadmill Test (BCTT) to prescribe a guided exercise prescription in those with PPCS safely sped recovery. The investigators have preliminary data that exercise may speed recovery if administered within the first week after sport-related concussion (SRC). Concussion is associated with adverse effects on the autonomic nervous system (ANS) and control of cerebral blood flow (CBF). The investigators have shown that sub-threshold aerobic exercise reduces symptoms in PPCS in association with normalization of ANS function and CBF control, providing a potential mechanism of action as well as target engagement for this non-pharmacological therapy. An important translational aspect is that the BCTT would be for clinicians a clinical proxy of concussion physiology that would help make the difficult return-to-activity/play decision more objective and physiologically-based. The investigators' long-term goals are to develop therapies that safely speed recovery from concussion, return youth back to their typical activities, actively prevent PPCS, and develop practical physiological tools for clinicians. The overall objective of this application is to determine if early guided aerobic exercise speeds recovery from SRC. The investigators specifically test underlying mechanisms of action for faster recovery by measuring ANS function (the cold pressor test, CPT) and CBF (by Arterial Spin Labeling, ASL). Age- and sex-matched healthy controls will be recruited to quantify physiological CBF differences and serve as a normative control group. The investigators will examine these questions in a randomized, multisite controlled trial in adolescents aged 13-18y with acute SRC by pursuing the following two specific aims: (1) determine if guided aerobic exercise/education speeds recovery after acute concussion in adolescents compared with (a) rest/education with a gradual return to activities, (i.e., current recommendation) and (b) a progressive stretching program/education (attention placebo); and (2) as secondary aims the investigators will quantify the effects of each intervention in Aim 1 on CBF and on autonomic function (CPT), which serve as relevant and objective physiological measures of autonomic regulation of CBF following concussion. This project will provide critical evidence to support the role of guided aerobic exercise for the active treatment of acute concussion and for a physiological mechanism(s) for its effect, which would lead to a paradigm shift from the current passive approach to treatment. The translational aspect of the project is unique and would have immediate impact to help clinicians determine recovery based on physiology rather than symptoms. A controlled active approach to concussion treatment may also substantially reduce the incidence of PPCS in children.

Recruitment & Eligibility

Status
WITHDRAWN
Sex
All
Target Recruitment
Not specified
Inclusion Criteria
  • 13-18 years; any race, ethnicity, or sex.
  • Concussion sustained 2-7 days prior to first clinical visit.
  • Symptom score (new symptoms) >3 on the Post-Concussion Symptom Inventory Scale.
  • Glasgow Coma Scale (GCS) of 13-15 (if available in medical record), an alteration in mental status, loss of consciousness (if present) of less than 30 minutes, and post-traumatic amnesia (if present) limited to <24 hours.
  • Low risk for cardiac disease and willing to exercise.
  • Medications, except for βeta- and calcium-blockers, are acceptable.
Exclusion Criteria
  • GCS score <13 at time of injury.
  • Lesion on CT/MRI (via review of emergency department records) and/or focal neurologic deficit consistent with an intracerebral lesion (e.g., unilateral weakness, dilated pupil).
  • Inability to exercise because of orthopedic injury, significant vestibular dysfunction, visual abnormality, or increased cardiac risk.
  • Neurosurgical intervention, general anesthesia and previously diagnosed neurological or psychiatric diseases.
  • Additional head injury after study enrollment.
  • Active substance abuse/dependence.
  • Non-fluency in English.
  • βeta- and calcium blocker use.
  • Autism, metal braces or other metal that would interfere with ASL.
  • Unwilling to exercise.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
StretchingStretchingStretching program that will not raise heart rate.
RestRestRelative rest. Avoid all structured exercise.
Aerobic ExerciseAerobic ExerciseSub-threshold aerobic exercise.
Primary Outcome Measures
NameTimeMethod
Time to recoveryup to 2 days

Time to baseline level of symptoms on Post Concussion Symptom Inventory (PCSI) for 2 days in a row

Secondary Outcome Measures
NameTimeMethod
Autonomic functionWithin one week of injury and at 1 month after injury

Autonomic function as assessed by the Cold Pressor Test (CPT)

Cerebral Blood Flow (CBF)Within one week of injury and at 1 month after injury

CBF by Arterial Spin Labelling MRI

Delayed recovery1 and 4 months after concussion

Persistence of increased symptoms on the PCSI at 1 and at 4 months after concussion

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