High-Dose Exercise for Concussion Recovery

(MEDIC Trial)

Recruiting at 2 trial locations

Overseen By Kelsie Richardson, MS

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Colorado, Denver

Disqualifiers: Neurological disorders, Exercise contraindications, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 8 weeks

216 Participants Needed

What You Need to Know Before You Apply

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.

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. ^{1 2 3 4 5}

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 7}

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. ^{2 3 6 8 9}

Who Is on the Research Team?

David R Howell, PhD

Principal Investigator

University of Colorado Denver | Anschutz

Are You a Good Fit for This Trial?

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

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)

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

Interventions

• High Dose Exercise

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.

How Is the Trial Designed?

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 United States, Canada, European Union for the following indications:

Approved in United States as Aerobic Exercise for:

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

Approved in Canada as Aerobic Exercise for:

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

Approved in European Union 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+

Boston Children's Hospital

Collaborator

Trials

801

Recruited

5,584,000+

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

Collaborator

Trials

2,103

Recruited

2,760,000+

Spaulding Rehabilitation Hospital

Collaborator

Trials

143

Recruited

11,200+

Published Research Related to This Trial

Adherence to a personalized aerobic exercise prescription within the first week after a sport-related concussion (SRC) is linked to faster recovery, with adherent adolescents recovering in a median of 12 days compared to 21.5 days for non-adherents.

Interestingly, those who adhered to the exercise regimen were more symptomatic and had lower exercise tolerance at the start, indicating that initial exercise intolerance, rather than symptom severity, influences adherence to the exercise program.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adolescents with Sport-Related Concussion Who Adhere to Aerobic Exercise Prescriptions Recover Faster. Chizuk, HM., Willer, BS., Cunningham, A., et al.[2023]

Early controlled aerobic exercise following a concussion is safe and does not adversely affect recovery, based on a review of 5 studies including randomized controlled trials and retrospective studies.

Implementing early aerobic exercise may lead to quicker returns to school and a reduction in symptom duration, suggesting it can positively impact recovery despite not always decreasing symptom intensity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Controlled Exercise and Timing of Treatment Following Concussion: A Critically Appraised Topic. Hattrup, N., Gray, H., Krumholtz, M., et al.[2021]

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]

Recent guidelines recommend a brief period of 24-48 hours of rest after a concussion, followed by the introduction of light-to-moderate aerobic exercise, which is considered safe and does not delay recovery.

Current literature suggests that engaging in aerobic exercise below symptom-exacerbating levels may improve recovery time from concussion, highlighting the need for further research to optimize exercise protocols and explore potential sex differences in recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of aerobic exercise following concussion: a narrative review. Cordingley, DM., Cornish, SM.[2023]

Subsymptom threshold aerobic exercise has been shown to improve symptoms in patients with postconcussion syndrome, based on a systematic review of 12 studies, indicating it may be a beneficial treatment option.

The exercise protocols typically involved 20 minutes of activity at 80% of the heart rate that triggered symptoms, performed 5-6 days a week, and no adverse events were reported, suggesting this approach is safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of Subsymptom Threshold Aerobic Exercise for Persistent Concussion Symptoms in Patients With Postconcussion Syndrome: A Systematic Review. McIntyre, M., Kempenaar, A., Amiri, M., et al.[2021]

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]

Graded aerobic treadmill testing is a safe and well-tolerated method for evaluating pediatric patients with sports-related concussions, with 97.9% of tests providing valuable clinical information and no serious complications reported.

In patients diagnosed with physiological post-concussion disorder, 90.2% showed clinical improvement after tailored submaximal exercise treatment, and 80.5% successfully returned to sports, highlighting the efficacy of this approach in managing concussion recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Graded aerobic treadmill testing in pediatric sports-related concussion: safety, clinical use, and patient outcomes. Cordingley, D., Girardin, R., Reimer, K., 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]

Citations

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]