Graded Exercise for Acute Phase Response

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Vanderbilt University Medical Center

Must not be taking: Anticoagulants, NSAIDs

Disqualifiers: Pre-existing conditions, Pregnancy, Smoking, others

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

Compensation: Varies

Number of Visits: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how different types of exercise affect the body's healing process. Researchers are examining how activities such as walking, running, or participating in a marathon (graded exercise) can promote tissue repair without excessive clotting. The goal is to identify the best type of exercise that aids healing while minimizing harm. This study targets healthy individuals who exercise regularly and are interested in basic exercises like walking and running or are already training for a marathon. As an unphased trial, it offers participants the chance to contribute to groundbreaking research on exercise and healing.

Will I have to stop taking my current medications?

If you are taking any anticoagulant medication or NSAID, you must stop using them at least 10 days before participating in the trial.

What prior data suggests that this exercise protocol is safe?

Research has shown that graded exercise can influence the body's response to stress or injury. This type of exercise might help balance certain immune cells and reduce inflammation. Studies indicate it is generally well-tolerated.

Regarding marathon running, studies have found that it can increase certain signs of inflammation in the body. This means the body shows signs of inflammation after such intense exercise. However, these reactions are normal and expected after running long distances. No clear evidence of serious harm from these changes exists, but they are important to be aware of.

Overall, the treatments involve different levels of exercise intensity, which are usually safe for healthy people. If there are any concerns, consulting a healthcare professional before joining a study is advisable. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how different exercise methods, including marathon participation and graded exercise, affect the body's acute phase response. Unlike traditional treatments that might rely on medication to manage inflammation and coagulation, this study seeks to understand how physical activity can naturally influence these processes. By examining both everyday activities like walking and more intense efforts like marathon running, the trial could reveal new, non-pharmacological ways to promote recovery and health after exercise. This could lead to more personalized and effective strategies for managing inflammation and blood clotting in active individuals.

What evidence suggests that this trial's exercises could be effective for improving global tissue health?

Research has shown that gradually increasing exercise, as participants may experience in the Graded Exercise arm, can positively affect inflammation. Studies have found significant reductions in markers like IL-6 and CRP, which indicate inflammation. This suggests that gradually increasing exercise might help manage inflammation and improve tissue health.

In the Marathon Participation arm, participants will run a marathon, which studies have shown can cause a noticeable increase in inflammation, including higher levels of markers like IL-6 and CRP. Although this might sound concerning, the body's response to this stress can provide insights into managing inflammation. This trial studies both types of exercise for their potential to balance inflammation and improve overall health. ^{1 2 3 5 6}

Who Is on the Research Team?

Jonathan Schoenecker, MD, PhD

Principal Investigator

Vanderbilt Orthopaedics

Are You a Good Fit for This Trial?

This trial is for healthy individuals aged 18-29 or 18-49, with a BMI of 18.5 to 30, who exercise regularly and are training for a marathon. It's not suitable for those on anticoagulants or NSAIDs recently, recent hospital patients, smokers/drug users, pregnant women, or anyone with acute health issues like infections.

Inclusion Criteria

You are planning to participate in a marathon.

The first group will do a 20-minute exercise that gradually increases in intensity.

Your body mass index (BMI) falls within a healthy range of 18.5 to 30.0.

Exclusion Criteria

You are pregnant.

You have used blood thinners or pain relievers like aspirin, ibuprofen, or naproxen within the last 10 days.

Recent inpatient admission within the last six months

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Graded Exercise

Participants engage in graded exercise sessions including rest, walking, and running to measure acute phase response changes

3 sessions of 20 minutes each

3 visits (in-person)

Marathon Participation

Participants complete a marathon with blood samples taken before, immediately after, and 1-2 days post-marathon to assess APR changes

1 day

1 visit (in-person) with follow-up blood draws

Follow-up

Participants are monitored for changes in coagulation, fibrinolysis, and inflammation post-exercise

2 days post-marathon

2 follow-up visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Graded Exercise
• Marathon participation

Trial Overview The study tests how different intensities of exercise affect the body's acute phase response (APR), which involves inflammation and blood clotting processes. Participants will engage in varying exercises from walking to running a marathon to see which promotes better tissue repair without triggering harmful coagulation.

How Is the Trial Designed?

Group I: Marathon Participation Experimental Treatment 1 Intervention

On the day of the marathon prior to start, the participant will be seated for 10 minutes prior to measuring their baseline heart rate. A 4.5 mL blood sample will be collected prior to initiation of exercise. Immediately after completion of the marathon, a 4.5 mL blood draw will be completed. Additional 4.5 mL blood draws will be taken at 1 and 2 days post-marathon to measure to length of time required to return to baseline coagulation, fibrinolysis, and inflammation following the prolonged, intense exercise.

Group II: Graded Exercise Experimental Treatment 1 Intervention

Volunteers will participate in 3 study visits. The study visits will consist either of 20 minutes of walking, 20 minutes of running or 20 minutes of sitting. At the beginning of each study visit, prior to any exercise, a 4.5mL blood sample will be collected. The participant will then complete either 20 minutes of walking, running or sitting and will then have a 4.5mL blood draw taken from a new site.

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12436102/

Effects of graded exercise rehabilitation on inflammatory ... Our results align with these established findings: both groups showed significant post-treatment reductions in serum IL-6, IL-8, TNF-α, and CRP ...

2. withpower.com withpower.com/trial/phase-acute-phase-reaction-10-2017-c96f7

Graded Exercise for Acute Phase Response This indicates that graded exercise might influence the acute-phase response, although the exact effects and benefits need further study.

3. frontiersin.org frontiersin.org/journals/medicine/articles/10.3389/fmed.2025.1620577/epub

Effects of graded exercise rehabilitation on inflammatory ... Our results demonstrate that graded exercise rehabilitation significantly increased CD3+, CD4+ percentages and CD4+/CD8+ ratios while reducing ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5568573/

Comparison of Graded Exercise and Graded Exposure ... Physical therapy supplemented with graded exercise or graded exposure resulted in equivalent clinical outcomes for pain intensity and disability.

5. sciencedirect.com sciencedirect.com/science/article/pii/S209525462400019X

The anti-inflammatory effects of exercise on autoimmune ... This review concluded that regular exercise programs reduced chronic inflammation and that single bouts of recommended amounts of moderate-to-vigorous exercise ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4715751/

The Acute Phase Inflammatory Response to Maximal ... Our results suggest maximal exercise may not be associated with any greater escalation of endothelial activation or inflammation in SCA and provide preliminary ...