Early Sub-threshold Exercise Treatment for Concussion

October 16, 2020 updated by: John J. Leddy MD, State University of New York at Buffalo

Guided Aerobic Exercise Therapy to Improve Recovery From Acute Concussion: A Randomized Controlled Trial

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

13 years to 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Aerobic Exercise
Sub-threshold aerobic exercise.
Behavioral: Aerobic Exercise
Progressive sub-threshold aerobic exercise
Placebo Comparator: Stretching
Stretching program that will not raise heart rate.
Behavioral: Stretching
Gentle progressive upper and lower extremity stretching program
Placebo Comparator: Rest
Relative rest. Avoid all structured exercise.
Behavioral: Rest
No structured exercise.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Time to recovery
Time Frame: up to 2 days
Time to baseline level of symptoms on Post Concussion Symptom Inventory (PCSI) for 2 days in a row
up to 2 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Autonomic function
Time Frame: Within one week of injury and at 1 month after injury
Autonomic function as assessed by the Cold Pressor Test (CPT)
Within one week of injury and at 1 month after injury
Delayed recovery
Time Frame: 1 and 4 months after concussion
Persistence of increased symptoms on the PCSI at 1 and at 4 months after concussion
1 and 4 months after concussion
Cerebral Blood Flow (CBF)
Time Frame: Within one week of injury and at 1 month after injury
CBF by Arterial Spin Labelling MRI
Within one week of injury and at 1 month after injury

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
State University of New York at Buffalo

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Children's Hospital of Philadelphia
Harvard University
The Mind Research Network

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 15, 2018

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 15, 2020

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 15, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 5, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 25, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 26, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 20, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 16, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 1 R01 NS106260-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings