Salivary Biomarkers for Concussion Recovery

Overseen By Haley Chizuk, MS, ATC

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: State University of New York at Buffalo

Must not be taking: ADHD, Depression, Anxiety medications

Disqualifiers: Neurological deficit, Cardiac risk, TBI, others

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

Compensation: Varies

Number of Visits: 4

Duration: 4 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests if exercise can help concussed adolescents recover by tracking changes in specific markers in their saliva. The study involves giving them specific exercise routines and measuring these markers to see if they indicate recovery.

Will I have to stop taking my current medications?

The trial excludes participants who are currently taking medications for ADHD, learning disorders, depression, anxiety, or other medications that can affect heart rate. If you are on these medications, you would not be eligible to participate.

Is aerobic exercise generally safe for humans?

High-intensity interval exercise (HIIE) can be safe for people with cardiovascular and metabolic diseases if they are clinically stable and have prior experience with moderate exercise, but it may have a higher risk of adverse responses compared to moderate exercise. Supervision and monitoring are recommended during and after exercise sessions. ^{1 2 3 4 5}

How does high volume and low volume aerobic exercise treatment differ from other treatments?

High volume and low volume aerobic exercise treatments are unique because they focus on varying the intensity and duration of exercise to improve cardiovascular health and fitness. Unlike traditional continuous exercise, these treatments can be more time-efficient and adaptable to different fitness levels, making them accessible for sedentary individuals. ^{6 7 8 9 10}

What data supports the effectiveness of the treatment High Volume Aerobic Exercise, Low Volume Aerobic Exercise?

Research shows that aerobic exercise, whether high or low volume, can improve fitness and heart health in patients with heart failure. Higher intensity aerobic exercise has been found to increase peak oxygen uptake, which is a key measure of cardiovascular fitness, more effectively than usual care. ^{11 12 13 14 15}

Who Is on the Research Team?

John Leddy, MD

Principal Investigator

University at Buffalo

Praveen Arany, DDS, PhD

Principal Investigator

University at Buffalo

Mohammad Nadir, MD, PhD

Principal Investigator

University at Buffalo

Barry Willer, PhD

Principal Investigator

University at Buffalo

Are You a Good Fit for This Trial?

Inclusion Criteria

Adolescent and adult athletes (age 13-18) diagnosed with SRC within 10 days of injury

Exclusion Criteria

You have had a serious brain injury in the past, which caused you to have a low score on the Glasgow Coma Scale.

You have signs of a specific brain or nerve problem.

Inability to exercise because of orthopedic or cervical spine injury

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Assessment

Participants undergo baseline assessments including the Buffalo Concussion Physical Exam and saliva collection

1 week

1 visit (in-person)

Treatment

Participants receive individualized exercise prescriptions based on the Buffalo Concussion Treadmill Test results

4 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for recovery and changes in salivary biomarkers

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• High Volume Aerobic Exercise
• Low Volume Aerobic Exercise

How Is the Trial Designed?

Group I: Concussed Participants Group 2 Experimental Treatment 1 Intervention

Low Volume Group

Group II: Concussed Participants Group 1 Experimental Treatment 1 Intervention

High Volume Group

Group III: Healthy controls Group 1 Active Control 1 Intervention

High Volume Group

Group IV: Healthy Controls Group 2 Active Control 1 Intervention

Low Volume Group

Who Is Running the Clinical Trial?

State University of New York at Buffalo

Lead Sponsor

Trials

279

Recruited

52,600+

National Center for Advancing Translational Sciences (NCATS)

Collaborator

Trials

394

Recruited

404,000+

Published Research Related to This Trial

High-intensity aerobic exercise training significantly improves peak oxygen consumption in heart failure patients, with a mean increase of 3.33 ml·kg(-1)·min(-1), which is a 23% improvement from baseline, compared to control groups.

No deaths were reported as directly attributable to exercise during the study, indicating that higher exercise intensity can be safely implemented in heart failure rehabilitation without increasing mortality risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcomes and cardiovascular responses to different exercise training intensities in patients with heart failure: a systematic review and meta-analysis. Ismail, H., McFarlane, JR., Nojoumian, AH., et al.[2022]

Aerobic interval training (AIT) significantly improved peak oxygen uptake in cardiac patients more than the usual care rehabilitation, with AIT participants showing an increase from 31.6 to 36.2 mL·kg(-1)·min(-1) compared to a smaller increase in the usual care group.

AIT was performed at a higher intensity (87.3% of peak heart rate) compared to the usual care group (78.7% of peak heart rate), suggesting that the increased intensity of AIT contributes to its greater effectiveness in enhancing exercise capacity and overall cardiovascular health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aerobic interval training increases peak oxygen uptake more than usual care exercise training in myocardial infarction patients: a randomized controlled study. Moholdt, T., Aamot, IL., Granøien, I., et al.[2022]

In a study of 28 heart failure patients, both low-volume time-based resistance exercise training (TRE) and aerobic moderate-intensity cycling (AMC) significantly improved exercise capacity and health-related quality of life after 6 weeks, with no differences between the two methods.

TRE required less time and energy expenditure compared to AMC, suggesting it could be a more time-efficient option for encouraging exercise adherence in patients with heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Effectiveness of Low-Volume Time-Efficient Resistance Training Versus Endurance Training in Patients With Heart Failure. Munch, GW., Rosenmeier, JB., Petersen, M., et al.[2019]

A systematic review of 11 studies involving 156 clinically stable patients with cardiometabolic diseases found that high-intensity interval exercise (HIIE) can lead to adverse responses in about 8% of individuals, indicating a higher risk compared to moderate-intensity exercise.

It is recommended that patients with cardiometabolic diseases who wish to engage in HIIE should be clinically stable, have prior experience with moderate-intensity exercise, and exercise under supervision to ensure safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What Doesn't Kill You Makes You Fitter: A Systematic Review of High-Intensity Interval Exercise for Patients with Cardiovascular and Metabolic Diseases. Levinger, I., Shaw, CS., Stepto, NK., et al.[2022]

In a randomized controlled trial involving 209 elderly participants (average age 80), a home-based exercise program was found to be generally safe, with 151 adverse events reported, affecting 47% of participants.

Despite the program's safety, 14% of the adverse events were serious, highlighting that high levels of pre-existing morbidity in this population can pose challenges to maintaining consistent exercise participation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in mobility-limited and chronically ill elderly adults participating in an exercise intervention study supported by general practitioner practices. Hinrichs, T., Bücker, B., Wilm, S., et al.[2015]

Researchers in resistance training studies often lack clear guidance and motivation for thorough adverse event (AE) reporting, which can lead to inconsistent practices.

There is a need for exercise-specific guidelines for AE reporting, as current standards are perceived as not applicable to exercise trials, highlighting the importance of tailored strategies to improve reporting consistency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Researchers' perspectives on adverse event reporting in resistance training trials: a qualitative study. El-Kotob, R., Pagcanlungan, JR., Craven, BC., et al.[2022]

In a 1.5-year study involving 274 male veterans with cardiovascular disease risk factors, only one serious adverse event (atrial fibrillation) occurred, indicating that a progressive walking program can be safely recommended for high-risk individuals.

While minor musculoskeletal issues were common, over half of the reported adverse events were unrelated to the exercise program, highlighting the need for strategies to help individuals with chronic illnesses safely resume physical activity after any health setbacks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events among high-risk participants in a home-based walking study: a descriptive study. Goodrich, DE., Larkin, AR., Lowery, JC., et al.[2022]

In a review of 113 randomized controlled trials involving 5909 participants with knee osteoarthritis, only 44.2% reported adverse events (AEs), indicating potential underreporting of exercise-related harm, which was found in 6.0% of participants with clear AE statements.

The study highlighted improvements in reporting AEs and dropouts (DOs) after the implementation of the CONSORT-2010 guidelines, but emphasized the need for clearer definitions and reporting standards to ensure the safety and efficacy of therapeutic exercise interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reporting of Harm in Randomized Controlled Trials of Therapeutic Exercise for Knee Osteoarthritis: A Systematic Review. von Heideken, J., Chowdhry, S., Borg, J., et al.[2023]

This pilot study involving 34 sedentary individuals demonstrated that low-volume high-intensity interval training (HIIT) protocols, performed just 2 times a week for 8 weeks, are feasible and well-tolerated in a community setting, with no adverse events reported.

Both 2×4-minute and 5×1-minute HIIT protocols significantly improved cardiovascular fitness (VO2max) by 20% and 27%, respectively, while requiring 60% less time than traditional moderate-intensity continuous training, highlighting their effectiveness for health promotion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of low-volume high-intensity interval training in a community setting: a pilot study. Reljic, D., Wittmann, F., Fischer, JE.[2018]

Citations

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

Clinical outcomes and cardiovascular responses to different exercise training intensities in patients with heart failure: a systematic review and meta-analysis. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Exercise training program characteristics and magnitude of change in functional capacity of heart failure patients. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

The effect of resistance training on clinical outcomes in heart failure: A systematic review and meta-analysis. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Aerobic interval training increases peak oxygen uptake more than usual care exercise training in myocardial infarction patients: a randomized controlled study. [2022]

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

Comparative Effectiveness of Low-Volume Time-Efficient Resistance Training Versus Endurance Training in Patients With Heart Failure. [2019]

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

What Doesn't Kill You Makes You Fitter: A Systematic Review of High-Intensity Interval Exercise for Patients with Cardiovascular and Metabolic Diseases. [2022]

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

Adverse events in mobility-limited and chronically ill elderly adults participating in an exercise intervention study supported by general practitioner practices. [2015]

8. Canada pubmed.ncbi.nlm.nih.gov

Researchers' perspectives on adverse event reporting in resistance training trials: a qualitative study. [2022]

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

Adverse events among high-risk participants in a home-based walking study: a descriptive study. [2022]

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

Reporting of Harm in Randomized Controlled Trials of Therapeutic Exercise for Knee Osteoarthritis: A Systematic Review. [2023]

11. Germany pubmed.ncbi.nlm.nih.gov

Low-volume, high-intensity, aerobic interval exercise for sedentary adults: VO₂max, cardiac mass, and heart rate recovery. [2021]

12. Germany pubmed.ncbi.nlm.nih.gov

Effects of low-volume high-intensity interval training in a community setting: a pilot study. [2018]

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

Effects of a low-volume aerobic-type interval exercise on VO2max and cardiac mass. [2022]

14. Germany pubmed.ncbi.nlm.nih.gov

Effect of preceding resistance exercise on metabolism during subsequent aerobic session. [2021]

15. Germany pubmed.ncbi.nlm.nih.gov

Effectiveness of low-intensity endurance training. [2013]