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

35 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to detail the precise temporal changes in the APR that occur in response to exercise in order to determine the types of exercise that confer maximal reparative fibrinolysis. Published research and preliminary studies conducted in our lab suggest that different types of exercise will preferentially activate fibrinolysis over coagulation, thereby promoting improved global tissue health \[8\]. As such, measuring markers of the APR in healthy individuals 1) at rest, 2) walking (light intensity exercise), 3) running (moderate intensity exercise), and 4) following endurance running (a marathon) will allow us to establish a baseline for the temporal changes in the APR that avoid activation of the procoagulant survival phase while maximizing the repair phase. Specific aims 1. To measure the acute phase response fibrinolysis, plasminogen consumption, and inflammatory profiles of healthy individuals before and after graded exercise (at rest, light intensity, medium intensity) and after prolonged exercise at medium intensity as defined by changes in fibrinolysis, plasminogen consumption, and inflammatory response. 2. To track the APR through modulated exercise in order to determine the type of exercise that enhances physiologic benefit and limits harm.

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 data supports the effectiveness of the treatment Graded Exercise, Marathon participation for Acute Phase Response?

Research suggests that strenuous exercise, like marathon running, can trigger changes in the body similar to the acute-phase response, such as increased levels of certain proteins and immune system activity. This indicates that graded exercise might influence the acute-phase response, although the exact effects and benefits need further study. ^{1 2 3 4 5}

Is graded exercise generally safe for humans?

Research suggests that regular exercise can help stabilize the body's stress and inflammatory responses, which may be beneficial for certain conditions. However, exercise can also cause changes in the body, such as increased levels of certain proteins, which should be considered when evaluating safety. ^{1 6 7 8 9}

How does the treatment 'Graded Exercise, Marathon participation' differ from other treatments for the acute phase response?

This treatment is unique because it involves participating in marathon running, which is a form of graded exercise that can trigger an acute phase response similar to that seen in certain medical conditions. Unlike traditional drug treatments, this approach uses physical activity to induce physiological changes, such as increased levels of C-reactive protein and other markers, which are typically associated with the body's response to inflammation or injury. ^{1 3 7 9 10}

Research Team

Jonathan Schoenecker, MD, PhD

Principal Investigator

Vanderbilt Orthopaedics

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

References

1. England pubmed.ncbi.nlm.nih.gov

The acute phase response and exercise: court and field sports. [2019]

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

Effects of acute-phase response on nutritional status and clinical outcome of hospitalized patients. [2013]

3. England pubmed.ncbi.nlm.nih.gov

Strenuous exercise: analogous to the acute-phase response? [2021]

4. Czech Republic pubmed.ncbi.nlm.nih.gov

[Acute phase reaction in severe injuries]. [2009]

5. England pubmed.ncbi.nlm.nih.gov

The acute phase protein response in patients receiving subcutaneous IL-6. [2019]

6. Spain pubmed.ncbi.nlm.nih.gov

The "bioregulatory effect of exercise" on the innate/inflammatory responses. [2018]

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

Evaluation of exercise-induced changes in concentrations of C-reactive protein and serum biochemical values in sled dogs completing a long-distance endurance race. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Effects of physical training on febrile and acute-phase responses induced in rats by bacterial endotoxin or interleukin-1. [2019]

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

C reactive protein concentrations during long distance running. [2019]

10. England pubmed.ncbi.nlm.nih.gov

The effects of menstrual cycle phases on immune function and inflammation at rest and after acute exercise: A systematic review and meta-analysis. [2023]