Passive Stretching for Peripheral Arterial Disease

Overseen By Jacob T Caldwell, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Wisconsin, La Crosse

Disqualifiers: Heart failure, Kidney disease, Crohn's, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: 12 weeks

64 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how passive stretching of the calf muscles can improve leg pain and walking ability in people with peripheral artery disease (PAD). PAD often causes pain during walking due to reduced blood flow, partly because of low nitric oxide levels. The study will examine how stretching affects inflammation and heart health, and whether combining it with dietary nitrate (such as nitrate-rich beetroot juice) can provide additional benefits. Suitable candidates for this trial have had PAD for at least three months, experience leg pain when walking, and have an ankle-brachial index of 0.90 or less, indicating reduced blood flow to the legs. Participants should not have engaged in regular exercise or undergone cardiovascular rehab in the past three months. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that gently stretching the calf muscles can be safe and helpful for people with peripheral artery disease (PAD). Earlier studies found that stretching improved blood flow and walking ability without causing serious side effects. Participants in these studies handled the stretching well, suggesting it is a safe option.

No major problems were reported, indicating that this treatment is safe. Additionally, stretching can help blood vessels become stronger during exercise, enhancing its safety.

This treatment is already in an advanced trial phase, indicating confidence in its safety. Overall, gentle stretching appears to be a well-tolerated and promising approach for PAD. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about passive stretching as a treatment for Peripheral Arterial Disease (PAD) because it offers a non-invasive way to improve blood flow and reduce inflammation. Unlike traditional treatments for PAD, which often include medications or surgical interventions to improve circulation, passive stretching targets the calf muscles directly. This method may enhance functional walking capacity by promoting muscle flexibility and circulation without the need for drugs or surgery. This makes it an appealing option for those looking for gentler, side-effect-free alternatives.

What evidence suggests that passive stretching and dietary nitrate could be effective for peripheral artery disease?

Research shows that gently stretching the calf muscles can increase blood flow and help people with peripheral artery disease (PAD) walk better. In this trial, participants will undergo passive stretching of the calf muscles to assess its effects on inflammation and functional walking capacity. Studies have found that this type of stretching improves the health of blood vessels. In older adults with stable PAD symptoms, passive stretching led to better walking ability. This treatment raises levels of nitric oxide, a substance that helps blood vessels relax and improves circulation. Overall, passive stretching seems promising for enhancing physical function in people with PAD. ^{1 2 3 4 6}

Who Is on the Research Team?

Jacob T Caldwell, Ph.D.

Principal Investigator

Assistant Professor

Are You a Good Fit for This Trial?

This trial is for individuals with Peripheral Arterial Disease (PAD), which causes leg pain and difficulty walking due to poor blood flow. Participants should be interested in exploring non-drug treatments like stretching and dietary changes to improve their condition.

Inclusion Criteria

Ankle-brachial index of 0.90 or less

My health condition has been stable for at least 3 months.

Exclusion Criteria

Beet allergy

I have kidney disease.

I have Crohn's disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo passive stretching of the calf muscles 5 days per week for 12 weeks, combined with dietary nitrate to enhance walking capacity

12 weeks

5 visits per week (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of functional capacity, inflammatory markers, and vascular function

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dietary Nitrate
• Passive Stretching

Trial Overview The study tests if passive calf muscle stretching, possibly combined with dietary nitrate supplements, can increase nitric oxide levels, reduce inflammation, and enhance walking ability in PAD patients over a period of 12 weeks.

How Is the Trial Designed?

Group I: Inflammation Experimental Treatment 2 Interventions

Blood and muscle biopsy samples pre/post passive stretching to assess local and systemic inflammation

Group II: Functional Walking capacity Experimental Treatment 2 Interventions

Passive stretching of the calf muscles 5 days per week for 12-weeks

Who Is Running the Clinical Trial?

University of Wisconsin, La Crosse

Lead Sponsor

Trials

5

Recruited

150+

Published Research Related to This Trial

A 90-minute session of passive leg movement in young healthy males significantly increased blood flow by 2.8 times without raising oxygen uptake, indicating that enhanced blood flow alone can stimulate physiological responses.

This passive movement led to a notable increase in vascular endothelial growth factor (VEGF) levels and endothelial nitric oxide synthase (eNOS) mRNA, suggesting that passive stretch and increased blood flow may promote capillary growth in muscle tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Passive leg movement enhances interstitial VEGF protein, endothelial cell proliferation, and eNOS mRNA content in human skeletal muscle. Hellsten, Y., Rufener, N., Nielsen, JJ., et al.[2020]

In a study involving eight male participants, passive stretching increased the range of motion (ROM) of the gastrocnemius medialis muscle by 4.6 degrees (17%) and significantly reduced the passive stiffness of the muscle-tendon unit (MTU) by 47%.

The increase in MTU elongation after conditioning stretches was primarily due to changes at the myotendinous junction, indicating that the connective tissue properties may be altered by passive stretching, rather than changes in tendon properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The acute effect of stretching on the passive stiffness of the human gastrocnemius muscle tendon unit. Morse, CI., Degens, H., Seynnes, OR., et al.[2022]

In a study involving eight patients with esophageal cancer, unilateral passive stretching of the gastrocnemius muscle before and after surgery was shown to affect blood volume in the non-stretched (contralateral) muscle, indicating a potential systemic effect of localized stretching.

The results suggest that while the stretched muscle experienced changes in blood volume during stretching, the contralateral muscle exhibited an inversely synchronized response, highlighting the need for further investigation into the underlying mechanisms of this phenomenon.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Change in Contralateral Muscle Blood Volume During Passive Unilateral Muscle Stretching Before and After Surgery. Kutsuzawa, T., Matsumoto, H., Kurita, D., et al.[2021]

A single bout of one-legged passive calf stretching in nine healthy young men led to an increase in shear rate in the posterior tibial artery during the relaxation period, suggesting improved blood flow dynamics.

The stretching caused a temporary decrease in arterial diameter during the stretch but did not affect shear rate or mean blood velocity until the relaxation phase, indicating that the hemodynamic response may help reduce arterial stiffness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute effect of passive one-legged intermittent static stretching on regional blood flow in young men. Yamato, Y., Higaki, Y., Fujie, S., et al.[2021]

Stretching the cat gastrocnemius muscle by 10-30% of its initial length increased its passive strength but decreased blood flow, which was more influenced by the level of passive tension than the amount of stretch.

After stretching, a postelongation hyperemia (increased blood flow) occurred, resembling the response seen after artery occlusion, but this response was significantly weaker than the increase in blood flow observed after muscle contractions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Changes in blood flow after longitudinal stretching of the cat m. gastrocnemius]. Matchanov, AT., Levtov, VA., Orlov, VV.[2014]

In a study involving 13 patients with peripheral arterial disease (PAD), daily passive calf muscle stretching for 4 weeks significantly improved endothelial function and walking ability, as measured by flow-mediated dilation (FMD) and the 6-minute walk test (6MWT).

The results showed that after stretching, FMD increased from 3.7% to 5.1% and walking distance improved from 182 meters to 304 meters, indicating that stretching can enhance blood flow and mobility in PAD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daily Passive Muscle Stretching Improves Flow-Mediated Dilation of Popliteal Artery and 6-minute Walk Test in Elderly Patients with Stable Symptomatic Peripheral Artery Disease. Hotta, K., Batchelor, WB., Graven, J., et al.[2020]

After 12 weeks of passive stretching training, participants showed significant improvements in vascular function and reduced arterial stiffness in both treated (femoral and popliteal) and untreated (brachial) arteries, indicating enhanced blood flow control mechanisms.

The benefits of passive stretching on vascular function were mostly temporary, as improvements related to central mechanisms returned to baseline within 6 weeks after training stopped, while local improvements persisted longer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence for improved systemic and local vascular function after long-term passive static stretching training of the musculoskeletal system. Bisconti, AV., Cè, E., Longo, S., et al.[2021]

Passive stretching for durations of 2, 4, or 8 minutes temporarily improved the range of motion (ROM) of the plantarflexors, with increases of 8% to 14% immediately after stretching, but these improvements returned to baseline within 10 minutes.

Isometric peak torque (PT) decreased slightly immediately after stretching but returned to baseline levels within 10 minutes, suggesting that while passive stretching may have short-term effects on muscle performance, it does not have a lasting detrimental impact.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Do practical durations of stretching alter muscle strength? A dose-response study. Ryan, ED., Beck, TW., Herda, TJ., et al.[2009]

An eight-week calf muscle stretching program significantly improved dorsiflexion range of motion and passive properties of the calf muscles in older women, indicating enhanced muscle flexibility and elasticity.

Participants in the stretching group also demonstrated improved performance in agility and walking speed, suggesting that the stretching program positively impacted their functional mobility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of an eight-week stretching program on the passive-elastic properties and function of the calf muscles of older women. Gajdosik, RL., Vander Linden, DW., McNair, PJ., et al.[2022]

Both prolonged static and cyclic calf stretching significantly reduced ankle joint stiffness in individuals with ischemic stroke, with a 35% decrease after static stretching and a 30% decrease after cyclic stretching.

Static stretching resulted in greater torque relaxation (53% more) compared to cyclic stretching, but neither stretching method improved walking speed in the participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of prolonged static and cyclic stretching on ankle joint stiffness, torque relaxation, and gait in people with stroke. Bressel, E., McNair, PJ.[2016]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6698217/

Daily Passive Muscle Stretching Improves Flow-Mediated ... Conclusions: Passive calf muscle stretching enhanced vascular endothelial function and improved walking function in elderly patients with stable symptomatic PAD ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S155383891930301X

Daily Passive Muscle Stretching Improves Flow-Mediated ... Conclusions. Passive calf muscle stretching enhanced vascular endothelial function and improved walking function in elderly patients with stable symptomatic PAD ...

3. withpower.com withpower.com/trial/phase-2-peripheral-arterial-disease-4-2024-da75d

Passive Stretching for Peripheral Arterial Disease Research shows that daily passive stretching of calf muscles can improve blood flow and walking ability in patients with peripheral arterial disease.

4. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06041880/passive-calf-stretching-therapy-in-peripheral-artery-disease

Passive Calf Stretching Therapy in Peripheral Artery Disease The goal of this clinical trial is to assess the effects of passive calf muscle stretching in patients diagnosed with peripheral artery ...

5. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0259444

Acute effects of the different relaxation periods during passive ... These findings suggest that the relaxation periods of intermittent static stretching that cause a high transient increase in shear rate (via reperfusion)

6. uwlax.edu uwlax.edu/currents/stretching-cardiovascular-research/

Stretching cardiovascular research - Currents A recent UWL study found that passive stretching before a workout can allow your blood vessels to be more resilient to the stress of exercise.