Clinical trial NCT06003855: Oxygen-guided Supervised Exercise Therapy
Official title: Oxygen-guided Supervised Exercise Therapy in Peripheral Artery Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Peripheral Artery Disease
Keywords: peripheral arterial disease
atherosclerosis
arterial occlusive disease
gait
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
Collaborators: name: University of Nebraska
First posted: 2023-08-22
Enrollment: 12
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Two groups will complete 12 weeks (36 sessions) of supervised exercise therapy. One group will complete the standard of care and the other group will complete the muscle oxygen guided supervised exercise therapy. Subjects will be randomly assigned to one of the two groups.
Primary purpose: BASIC_SCIENCE

Brief summary: Peripheral artery disease (PAD) is a cardiovascular disease manifesting from systemic atherosclerosis, which blocks the leg arteries and results in insufficient blood flow to the lower extremities. Limb ischemia from PAD is the most common disorder treated within the vascular surgery service at the Omaha Veterans' Affairs Medical Center. PAD also accounts for one-third of the operations performed in the VA Medical Centers nationwide. This project aims to establish the feasibility and acceptability of a muscle oxygen-guided supervised exercise program for patients with PAD. The investigators will determine the potential benefits of using this intervention over standard supervised exercise therapy. This modified intervention may enable patients to increase overall physical activity without the negative impacts on muscle structure and function. Increasing physical activity will decrease cardiovascular morbidity and mortality. If proven beneficial, the findings will lead to an improved exercise program that directly benefits veterans nationwide.

Detailed description: The long-term goal of this research is to improve mobility, functional independence, and quality of life in patients with peripheral artery disease (PAD) by developing conservative interventions. PAD is a manifestation of atherosclerosis, which produces blockages in the leg arteries, and results in insufficient blood flow to the legs. PAD results in significant gait deficits and an overall sedentary lifestyle. The investigators' prior work showed that the biochemical (oxidative stress and mitochondrial dysfunction) and histological (myofiber degeneration and fibrosis) characteristics of PAD muscles are altered compared to controls. These myopathic changes are due to cycles of ischemia and reperfusion, and they correlate to functional limitations (walking distance and calf muscle strength). Limb ischemia from PAD is the most common disorder treated within the vascular surgery service of the Omaha Veterans Affairs Medical Center. The most effective treatment for increasing the distances that patients with PAD can walk is supervised exercise therapy (SET). However, SET uses pain onset to guide exercise intensity and rest cycles. These repeated bouts of ischemia/reperfusion could cause further pathological damage to muscle myofibers and oxidative processes. Such adverse effects of ischemia may explain why not all patients improve with SET. Preventing cycles of ischemia-reperfusion during SET can improve walking performance without further muscle biochemistry damage in patients with PAD. The investigators propose using hemodynamic responses to modulate exercise intensity and prevent ischemia during SET. Muscle oxygen-guided supervised exercise therapy (M-SET) can prevent ischemia onset and thus preserve muscle mass and function during exercise therapy in patients with PAD. The aims are:

Aim 1: To determine the exercise outcomes of an M-SET versus a standard SET session in patients with PAD. Aim 2: To determine the acute effect of M-SET versus standard SET on oxidative stress and inflammation in patients with PAD. Aim 3: To determine the effect of 12 weeks of M-SET versus standard SET on exercise outcomes, muscle biochemistry, and subject-reported preference in patients with PAD.

The investigators will measure exercise outcomes during one session each of M-SET (using StO2 on the calf to modulate exercise) and SET, in 12 patients with PAD using a cross-over design. Exercise outcomes will be assessed by the total distance patients walked during the session, metabolic cost, metabolic equivalents of the task, physical activity enjoyment, and rate of perceived exertion. In Aim 2, oxidative stress will be measured using peripheral blood mononuclear cells before and after each exercise session (SET and M-SET) in all patients. During the standard SET session, subjects will walk until claudication pain becomes severe and the participant needs to stop. Then subjects will rest until claudication pain subsides. Afterward, subjects will walk again, repeating the cycle for up to 50 minutes. M-SET will use an StO2 threshold that is 15% lower level than baseline StO2 levels. Subjects will stop walking once they reach the threshold and rest until StO2 levels return to baseline. Then, subjects will begin walking again, repeating this cycle for 50 total minutes (including walking and rest). Patients from Aims 1 and 2 will be randomly assigned to either a 12-week M-SET or standard SET (6 per group) program. Training will be performed three times weekly as described above. Subjects will be evaluated before and after the intervention to capture initial and absolute walking distances and 7-day physical activity. Muscle biochemistry will be quantified using mitochondrial function, mitochondrial oxidative dynamics, and reactive oxygen species production before and after training. Results will support a full clinical trial and rehabilitation recommendations.

Eligibility criteria: Inclusion Criteria:

At entry into the study, all subjects must:

* Be able to give written, informed consent
* Have documented lower extremity arterial occlusive disease based on ankle/brachial index measurements and/or arterial imaging
* Demonstrate positive history of chronic claudication
* Have a stable blood pressure regimen, stable lipid regimen, stable diabetes regimen and risk factor control for 6 weeks

Exclusion Criteria:

Any potential subjects will be excluded if they have:

* Rest pain or tissue loss due to PAD (Fontaine stage III and IV)
* Acute lower extremity ischemic event secondary to thromboembolic disease or acute trauma
* Walking capacity limited by conditions other than claudication including leg (joint/musculoskeletal, neurologic) and systemic (heart, lung disease) pathology

Primary outcomes:
measure: Distance walked
timeFrame: Before and after 12 week exercise program
measure: Energy expenditure
timeFrame: Before and after 12 weeks after the exercise program
measure: Reactive oxygen species
timeFrame: Before exercise, immediately after exercise, 30 minutes after exercise, and 1 hour after exercise
measure: Protein expression of ROS-related enzymes
timeFrame: Before exercise, immediately after exercise, 30 minutes after exercise, and 1 hour after exercise
measure: Markers of systemic inflammation
timeFrame: Before exercise, immediately after exercise, 30 minutes after exercise, and 1 hour after exercise
measure: Initial and absolute walking distances
timeFrame: Before and after 12 week supervised exercise program
measure: Comprehensive mitochondrial respiratory complex function
timeFrame: Before and after 12 week supervised exercise program
measure: Mitochondrial dynamics
timeFrame: Before and after 12 week supervised exercise program
measure: Mitochondrial reactive oxygen species production
timeFrame: Before and after 12 week supervised exercise program
Secondary outcomes:
measure: Metabolic equivalents of task
timeFrame: Immediate
measure: Physical activity enjoyment scale
timeFrame: Immediate
measure: Rating of perceived exertion
timeFrame: Immediate
measure: Physical activity average steps/day
timeFrame: Before and after 12 week supervised exercise program
measure: Muscle strength
timeFrame: Before and after 12 week supervised exercise program
measure: Acceptability
timeFrame: Before and after 12 week supervised exercise program
measure: Maximum cadence/day
timeFrame: Before and after 12 week supervised exercise program
measure: Muscle endurance
timeFrame: Before and after 12 weeks supervised exercise program.
Other outcomes:
Locations:
city: Omaha
country: United States
facility: Omaha VA Nebraska-Western Iowa Health Care System, Omaha, NE
state: Nebraska
Study officials:
affiliation: Omaha VA Nebraska-Western Iowa Health Care System, Omaha, NE
name: Iraklis I Pipinos, MD
role: PRINCIPAL_INVESTIGATOR
References: