High-Dose Exercise for Concussion Recovery

(MEDIC Trial)

Recruiting in Palo Alto (17 mi)

+2 other locations

Overseen by David R Howell, PhD

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of Colorado, Denver

Disqualifiers: Neurological disorders, Exercise contraindications, others

No Placebo Group

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

Aerobic exercise has emerged as an effective treatment to reduce sport-related concussion symptom severity, yet existing work lacks rigor regarding the precise exercise volume and intensity required to elicit therapeutic effects, how exercise can alter concussion-related pathophysiology, and whether exercise can prevent the development of secondary sequelae. Our objective is to examine if a high dose exercise program (higher volume than currently prescribed at an individualized, safe intensity level) initiated within 14 days of concussion results in faster symptom resolution, altered physiological function, or reduced secondary sequalae. Findings from this research will lead to more rigorous and precise rehabilitation guidelines and improved understanding about how exercise affects neurophysiological function among adolescents with concussion.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment High Dose Exercise, Aerobic Exercise, High-Intensity Aerobic Exercise, Subsymptom Threshold Aerobic Exercise for concussion recovery?

Research suggests that aerobic exercise, when done below the level that worsens symptoms, can help speed up recovery from a concussion. Studies have shown that early controlled aerobic exercise is safe and may reduce the duration of symptoms, helping individuals return to normal activities faster. ^{1 2 3 4 5}

Is high-dose exercise safe for concussion recovery?

Research shows that controlled aerobic exercise is generally safe for concussion recovery, with no adverse effects reported in several studies. It may even help reduce symptoms and improve psychological well-being. ^{2 3 6 7 8}

How does high-dose exercise differ from other treatments for concussion recovery?

High-dose exercise for concussion recovery is unique because it involves aerobic exercise at a level just below the threshold that would trigger symptoms, which is different from the traditional approach of complete rest. This method aims to improve recovery by gradually reintroducing physical activity, potentially reducing symptoms and improving psychological well-being without adverse effects. ^{1 2 3 6 9}

Research Team

David R Howell, PhD

Principal Investigator

University of Colorado Denver | Anschutz

Eligibility Criteria

This trial is for teens aged 13-18 who have been diagnosed with a concussion by a sports medicine physician and are still experiencing symptoms (PCSS score >10). It's not suitable for those with pre-existing neurological disorders, exercise contraindications, or another concussion in the last 6 months.

Inclusion Criteria

I am between 13 and 18 years old.

Post-Concussion Symptom Scale (PCSS) score >10 to ensure participants are not recovered by enrollment

Concussion diagnosis by a sports medicine physician

Exclusion Criteria

Pre-existing neurological disorders

Exercise contraindications

Concussion <6 months before enrollment (excluding the current injury)

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Treatment

Participants are randomized to high dose aerobic exercise or standard-of-care, with exercise recommendations adjusted upon symptom resolution

8 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including serum biomarker and cerebrovascular function assessments

8 weeks

2 visits (in-person)

Treatment Details

Interventions

• High Dose Exercise (Behavioral Intervention)

Trial Overview The study tests if starting a high dose of aerobic exercise within two weeks after getting a concussion can speed up symptom recovery, change physiological functions, or prevent issues like depression and anxiety that sometimes follow concussions.

Participant Groups

Group I: High Dose Exercise Experimental Treatment 1 Intervention

The investigators will provide exercise dose recommendations for initial visit until symptom resolution, and revise upon symptom resolution (to use for the subsequent 8 weeks). These include intensity (target HR) and volume (frequency/duration). Intensity is calculated as 90% of the HR at the end of the exercise test. The volume recommendation is 150 mins/week (\~30 min/day; 5 days/week). The mode of exercise is another consideration. This will be left to participant preference, so that the investigators do not exclude potential participants due to lack of access to specific exercise equipment.

Group II: Standard-of-care Active Control 1 Intervention

Participants are instructed to perform activity in line with physician recommendations. This consists of a general recommendation (no specific HR/volume) or symptom limited physical activity.

High Dose Exercise is already approved in Canada for the following indications:

Approved in Canada as Aerobic Exercise for:

• Sport-related concussion recovery
• Reduction of concussion symptom severity

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

Aviva Abosch

University of Colorado, Denver

Chief Medical Officer since 2019

MD

Uday B. Kompella

University of Colorado, Denver

Chief Executive Officer since 2015

PhD in Pharmaceutical Sciences

Boston Children's Hospital

Collaborator

Trials

801

Recruited

5,584,000+

Dr. Kevin B. Churchwell

Boston Children's Hospital

Chief Executive Officer since 2021

MD from Vanderbilt Medical School

Dr. Sarah Pitts

Boston Children's Hospital

Chief Medical Officer since 2019

MD from Harvard Medical School

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

Dr. Diana W. Bianchi

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Chief Executive Officer since 2016

MD from Stanford University

Dr. Alison Cernich

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Chief Medical Officer since 2020

PhD in Clinical Psychology from University of Maryland

Spaulding Rehabilitation Hospital

Collaborator

Trials

143

Recruited

11,200+

Greg Jackson

Spaulding Rehabilitation Hospital

Interim President and Chief Operating Officer

Bachelor's degree in Psychology and Master's in Rehabilitation Counseling from Arkansas State University

Cheri Blauwet

Spaulding Rehabilitation Hospital

Chief Medical Officer

MD

Findings from Research

Aerobic exercise is increasingly recognized as a beneficial rehabilitation technique for individuals recovering from concussions, as it can help reduce symptoms and improve overall function.

The review highlights that while exercise is promising, the optimal parameters for recovery—such as frequency, duration, and intensity—are still not well defined, indicating a need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of Aerobic Exercise in Reducing Persistent Sport-related Concussion Symptoms. Howell, DR., Taylor, JA., Tan, CO., et al.[2020]

A study involving 12 patients with post-concussion syndrome showed that subsymptom threshold exercise training is safe and leads to significant improvements in exercise capacity and reduction of PCS symptoms over 2 to 3 weeks.

Participants were able to exercise longer and at higher heart rates without exacerbating symptoms, with athletes recovering faster than nonathletes, indicating that controlled exercise can be an effective treatment for PCS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A preliminary study of subsymptom threshold exercise training for refractory post-concussion syndrome. Leddy, JJ., Kozlowski, K., Donnelly, JP., et al.[2022]

In a study of 65 adolescent athletes with sport-related concussions, a dynamic supervised exercise challenge (DSEC) was more effective at uncovering concussion symptoms than a basic aerobic supervised exercise challenge (ASEC), with 37% of previously asymptomatic patients developing symptoms during the DSEC.

The findings suggest that incorporating dynamic exercises into concussion assessments can enhance symptom detection, which is crucial for guiding safe return-to-play decisions in young athletes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Symptom Provocation During Aerobic and Dynamic Supervised Exercise Challenges in Adolescents With Sport-Related Concussion. Popovich, M., Sas, A., Almeida, AA., et al.[2022]

In a study involving 75 amateur athletes (45 females and 30 males), light aerobic exercise after a concussion led to increased reports of balance problems and somatic symptoms for both genders, indicating that some symptoms may temporarily worsen post-exercise.

Women experienced significant reductions in emotional symptoms like irritability and sadness after aerobic exercise, while men did not show significant changes in headache or emotional symptoms, highlighting important sex differences in symptom response post-concussion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sex differences in self-reported symptoms after aerobic exercise in non-injured athletes: implications for concussion management programmes. Gaetz, MB., Iverson, GL.[2009]

References

1. United States pubmed.ncbi.nlm.nih.gov

Adolescents with Sport-Related Concussion Who Adhere to Aerobic Exercise Prescriptions Recover Faster. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Early Controlled Exercise and Timing of Treatment Following Concussion: A Critically Appraised Topic. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

The Role of Aerobic Exercise in Reducing Persistent Sport-related Concussion Symptoms. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

A preliminary study of subsymptom threshold exercise training for refractory post-concussion syndrome. [2022]

5. Canada pubmed.ncbi.nlm.nih.gov

Efficacy of aerobic exercise following concussion: a narrative review. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

The Role of Subsymptom Threshold Aerobic Exercise for Persistent Concussion Symptoms in Patients With Postconcussion Syndrome: A Systematic Review. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Symptom Provocation During Aerobic and Dynamic Supervised Exercise Challenges in Adolescents With Sport-Related Concussion. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Graded aerobic treadmill testing in pediatric sports-related concussion: safety, clinical use, and patient outcomes. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Sex differences in self-reported symptoms after aerobic exercise in non-injured athletes: implications for concussion management programmes. [2009]