Precision Exercise Training for Sepsis

(PRECISE Trial)

Overseen By John Boyd, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of British Columbia

Must not be taking: Immunomodulatory drugs

Disqualifiers: Diabetes, Autoimmune diseases, Hypertension, others

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

Compensation: Varies

Number of Visits: 48

Duration: 12 weeks

32 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a 12-week exercise program, called Precision Exercise Training, can help sepsis survivors improve their exercise capacity. The program combines strength and aerobic exercises tailored to each participant's needs. Researchers will compare participants to a group receiving general lifestyle advice without the exercise program. The trial seeks individuals who have been recovering from sepsis for at least two months, have lower than normal fitness levels, and can commit to exercising three times a week for 12 weeks. As an unphased trial, this study offers participants a unique opportunity to contribute to innovative research that could enhance recovery strategies for sepsis survivors.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on daily immunomodulatory drugs, you cannot participate in the trial.

What prior data suggests that this precision exercise training is safe for sepsis survivors?

Research shows that exercise programs are generally safe and manageable. In past studies, similar exercise routines did not cause serious side effects, and participants handled the exercises well. Reports of harm or negative effects were minimal.

Exercise, including activities that build strength and improve heart health, offers many benefits. It supports heart health, increases muscle strength, and enhances overall well-being. These benefits are well-documented, and exercise is often part of health recovery plans.

This trial aims to provide personalized exercise plans for people recovering from sepsis, seeking to determine if these plans enhance exercise effectiveness. Since exercise is generally safe when done correctly and with guidance, it is unlikely to cause harm. However, participants should carefully follow instructions to avoid injury. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about precision exercise training for sepsis because it offers a novel approach to recovery that differs from traditional treatments like antibiotics and supportive care. This intervention tailors physical exercise specifically to individual patients, potentially enhancing their recovery by improving physical function and overall health. Unlike standard treatments that primarily address the infection and its symptoms, precision exercise training focuses on personalized rehabilitation, which could lead to better long-term outcomes and quality of life for sepsis survivors.

What evidence suggests that precision exercise training is effective for improving exercise tolerance in sepsis survivors?

Research has shown that exercise can benefit sepsis survivors. One study found that a personalized exercise plan improved their exercise capacity and strengthened their immune system. Another study demonstrated that combining cardio and strength exercises enhanced overall physical health in individuals recovering from serious illnesses like sepsis. In this trial, participants in the exercise intervention arm will undergo a 12-week tailored exercise program, which may help sepsis survivors become stronger and more physically fit. ^{1 2 3 5 6}

Who Is on the Research Team?

Graeme Koelwyn, PhD

Principal Investigator

University of British Columbia

Are You a Good Fit for This Trial?

This trial is for sepsis survivors over 19 years old with reduced cardiorespiratory fitness, who can commit to a 12-week exercise program. They must have had symptoms like fast breathing, confusion, or low blood pressure. It's not for those on oxygen therapy, recent heart events, uncontrolled conditions like diabetes or hypertension, pregnant women, or those unable to consent.

Inclusion Criteria

Signed informed consent

My heart and lung fitness is below 80% of what's expected for my age and sex.

≥60 days prior to study enrollment, known or suspected infection that includes at least two of the following clinical criteria that together constitute a new bedside clinical score termed quickSOFA (qSOFA): respiratory rate >22breaths/min, altered mentation, or systolic blood pressure <100mmHg

Exclusion Criteria

Desaturation during exercise SpO2<85%

Known pregnancy/ intending to get pregnant within 28 days of enrolling in the study or breastfeeding

Cardiovascular contraindication or musculoskeletal limitations to exercise as assessed during the cardiopulmonary exercise test

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants complete 12-weeks of precision exercise training consisting of individualized, nonlinear periodized strength and aerobic exercise training

12 weeks

36 sessions (in-person)

Attention Control

Participants in the control group receive usual care procedures and general lifestyle advice 1x per week

12 weeks

12 contacts (virtual)

Follow-up

Participants are monitored for changes in clinical biomarkers and health-related quality of life

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Precision Exercise Training

Trial Overview Researchers are testing if a personalized 12-week exercise program helps improve the ability of sepsis survivors to tolerate physical activity compared to usual care and lifestyle advice. Participants will do strength and aerobic exercises three times weekly and their progress will be measured against an attention control group.

How Is the Trial Designed?

Group I: Exercise Intervention Experimental Treatment 1 Intervention

Patients will participate in a 12-week (36 sessions) precision exercise training intervention

Group II: Attention Control Active Control 1 Intervention

Patients will not receive exercise training but will be contacted 1x per week via phone to document self-reported physical activity and general wellbeing.

Who Is Running the Clinical Trial?

University of British Columbia

Lead Sponsor

Trials

1,506

Recruited

2,528,000+

St. Paul's Hospital, Canada

Collaborator

Trials

48

Recruited

13,200+

Providence Health & Services

Collaborator

Trials

131

Recruited

827,000+

Vancouver Coastal Health Research Institute

Collaborator

Trials

30

Recruited

5,600+

Simon Fraser University

Collaborator

Trials

59

Recruited

12,500+

Published Research Related to This Trial

Aerobic exercise training significantly protects against sepsis-associated acute kidney injury (AKI) by enhancing the expression of R-spondin 3 (RSPO3), which helps maintain kidney function and integrity during sepsis.

The study found that exercise or RSPO3 administration reduced inflammation and endothelial damage in the kidneys, while knocking out RSPO3 worsened kidney injury, highlighting its crucial role in protecting against LPS-induced renal complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased R-spondin 3 contributes to aerobic exercise-induced protection against renal vascular endothelial hyperpermeability and acute kidney injury. Xu, QF., Zhang, H., Zhao, Y., et al.[2023]

In a 12-week randomized controlled trial with 119 healthy young adults, aerobic exercise training did not lead to expected decreases in inflammatory markers TNF-α and IL-6, despite participants showing a 15% increase in aerobic capacity.

Interestingly, the study found that exercise initially increased levels of TNF-α and IL-6 in response to certain lipopolysaccharide levels, suggesting that aerobic training may provoke a temporary proinflammatory response rather than an anti-inflammatory effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aerobic Exercise Training and Inducible Inflammation: Results of a Randomized Controlled Trial in Healthy, Young Adults. Sloan, RP., Shapiro, PA., McKinley, PS., et al.[2023]

In a study involving 34 middle-aged obese men, both nonlinear resistance training (NRT) and aerobic interval training (AIT) significantly improved aerobic capacity compared to a sedentary control group, with AIT showing superior results in maximal oxygen uptake.

While both training types effectively reduced insulin resistance, AIT demonstrated better anti-inflammatory effects, as indicated by a significant increase in the IL-10:TNF-α ratio compared to the control group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of nonlinear resistance and aerobic interval training on cytokines and insulin resistance in sedentary men who are obese. Nikseresht, M., Agha-Alinejad, H., Azarbayjani, MA., et al.[2022]

Survivors of severe sepsis and septic shock showed significant physical inactivity during hospitalization, spending 90% of their time lying or sitting, which improved to 58% three months after discharge but still remained lower than healthy individuals.

Muscle strength and exercise capacity in these patients were only about 54% of predicted values at discharge, improving to 70% after three months, indicating a slow recovery process influenced negatively by factors like systemic corticosteroid use and longer hospital stays.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physical activity, muscle strength, and exercise capacity 3 months after severe sepsis and septic shock. Borges, RC., Carvalho, CR., Colombo, AS., et al.[2022]

Mice that engaged in low-intensity exercise during the acute phase of sepsis showed higher survival rates compared to sedentary mice, indicating that exercise may have a protective effect during sepsis.

Exercise increased fatty acid oxidation and levels of PGC-1α, a protein associated with energy metabolism, suggesting that physical activity helps mobilize energy sources and may improve outcomes in sepsis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-intensity exercise in the acute phase of lipopolysaccharide-induced sepsis improves lipid metabolism and survival in mice by stimulating PGC-1α expression. Irahara, T., Sato, N., Inoue, K., et al.[2018]

Individualizing exercise prescriptions is crucial for maximizing safety and effectiveness, as it helps reduce risks of injury and cardiac emergencies during exercise.

The effectiveness of exercise programs should be measured by improvements in aerobic power, muscular strength, and overall health, but patient responses can vary significantly, necessitating adjustments based on individual reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise prescription: principles and current limitations. Shephard, RJ.[2021]

Resistance training (RT) is effective in increasing adiponectin levels and decreasing leptin and C-reactive protein levels, particularly in overweight and obese individuals, as shown in a systematic review of 17 studies.

Women may respond more positively to RT in terms of adiponectin, leptin, and C-reactive protein levels, and longer training durations (16 weeks or more) and higher intensities (over 80% of one repetition maximum) enhance these effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of resistance training on cytokines. de Salles, BF., Simão, R., Fleck, SJ., et al.[2018]

Inadequate exercise significantly increases the risk of sepsis mortality, with a 2.24-fold higher risk for sepsis as an underlying cause and a 2.11-fold higher risk when sepsis is a contributing factor, based on a study of 155,484 participants over an average of 11.6 years.

The risk associated with inadequate exercise is particularly pronounced in individuals with diabetes, showing a 4.78-fold increase in sepsis mortality risk, highlighting the importance of regular physical activity for this vulnerable group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inadequate exercise as a risk factor for sepsis mortality. Williams, PT.[2021]

Early exercise rehabilitation combined with standard sepsis treatment showed potential benefits for functional recovery in patients with severe sepsis, particularly at hospital discharge.

In patients with higher severity scores (APACHE II ≥10), those who received the rehabilitation intervention demonstrated significantly greater improvements in physical function, as measured by the Modified Barthel Index and Functional Independence Measure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Early Exercise Rehabilitation on Functional Recovery in Patients with Severe Sepsis. Ahn, JY., Song, JE., Ann, HW., et al.[2019]

Exercise training significantly lowers baseline arterial pressure, heart rate, and levels of harmful substances like methyl guanidine in rats, suggesting a protective effect against stress.

In response to endotoxin-induced sepsis, exercise-trained rats showed reduced inflammation and less severe damage to the heart, liver, and lungs compared to sedentary controls, indicating that exercise may help mitigate organ injury during septic conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise training attenuates septic responses in conscious rats. Chen, HI., Hsieh, SY., Yang, FL., et al.[2013]

In a study of 516 sepsis patients admitted to the ICU, those with low skeletal muscle mass who received ICU-rehabilitation had significantly lower in-hospital and 6-month mortality rates compared to those who did not receive rehabilitation (26.0% vs. 39.8% and 38.6% vs. 51.5%, respectively).

ICU-rehabilitation was found to be independently associated with a 34% reduction in 1-year mortality for patients with low skeletal muscle mass, highlighting the importance of early rehabilitation in this vulnerable group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ICU rehabilitation is associated with reduced long-term mortality from sepsis in patients with low skeletal muscle mass: a case control study. Kim, T., Huh, S., Kim, SY., et al.[2022]

Dynamic strength training, especially at high intensities (≥70% of one-repetition maximum), significantly enhances muscle strength and power output in patients with cardiovascular disease, which can improve their overall prognosis.

High-intensity strength training is associated with fewer increases in blood pressure and cardiac output compared to low-intensity training, suggesting it may be a safer option for the cardiovascular system while still being effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dynamic strength training intensity in cardiovascular rehabilitation: is it time to reconsider clinical practice? A systematic review. Hansen, D., Abreu, A., Doherty, P., et al.[2020]

Three weeks of moderate exercise training significantly improved survival rates in rats subjected to sepsis, indicating that fitness may be a modifiable risk factor for surgical outcomes.

The exercise training reduced inflammation and oxidative stress in the liver, restoring important antioxidant pathways, which suggests that exercise may enhance the body's immune response during systemic infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Moderate exercise-induced dynamics on key sepsis-associated signaling pathways in the liver. Osuru, HP., Ikeda, K., Atluri, N., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05784740

Precision Exercise to Improve Outcomes in Sepsis The goal of this interventional clinical research study is to assess the efficacy of a 12-week precision exercise training intervention to improve exercise ...

2. withpower.com withpower.com/trial/phase-toxemia-2-2023-1d2d3

Precision Exercise Training for Sepsis (PRECISE Trial) This trial tests a personalized exercise program for sepsis survivors to see if it improves their ability to exercise and boosts their immune system.

3. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05784740/precision-exercise-to-improve-outcomes-in-sepsis

Precision Exercise to Improve Outcomes in Sepsis The goal of this interventional clinical research study is to assess the efficacy of a 12-week precision exercise training intervention to improve exercise ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6647016/

Exercise Training Mitigates Multisystem Deconditioning ... This study investigated the safety and effectiveness of a new integrated aerobic and resistance exercise training prescription (SPRINT) using two different ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06922981

Periodized Resistance and Aerobic Training in Non ... The aim of the study is to compare the effectiveness of two forms of periodized exercise training programs (resistance and aerobic ) using ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9277456/

Roles and Molecular Mechanisms of Physical Exercise in ... In this review, we discuss the effects of physical exercise on multiple organ functions and the short- and long-time outcomes of sepsis.