Intermittent Pneumatic Compression + Exercise for Peripheral Arterial Disease

(INTERCEDE Trial)

Recruiting at 3 trial locations

Overseen By Kathryn Domanchuk, BS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Northwestern University

Disqualifiers: Amputation, Critical limb ischemia, Wheelchair, others

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

Compensation: Varies

Number of Visits: 6

Duration: 6 months

230 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to help people with lower extremity peripheral artery disease (PAD) walk longer distances. It combines home-based walking exercises with intermittent pneumatic compression, similar to a special leg massage. The study compares this combination to exercise alone and a placebo version of the compression therapy to determine its effectiveness. People with PAD who have difficulty walking due to their condition might be suitable for this trial. As an unphased trial, participants can contribute to innovative research that could enhance walking ability for those with PAD.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you started taking cilostazol within the last three months, you may need to wait until three months have passed to be eligible.

What prior data suggests that this intermittent pneumatic compression device is safe for people with peripheral arterial disease?

A previous study found that devices called intermittent pneumatic compression (IPC) are safe and effective for various medical uses. They reduce the risk of blood clots in the legs, which benefits less active individuals. This indicates that IPC is generally well-tolerated.

Research into exercise therapy for people with peripheral artery disease (PAD) has also shown positive results. Exercise therapy is a common treatment for PAD, offering proven benefits with minimal risks. One study reported very low rates of major heart-related issues during exercise sessions, indicating that exercise is generally safe for most people.

These findings suggest that using IPC along with exercise is likely safe for most participants. However, as with any treatment, individual responses can vary, so discussing any concerns with a healthcare provider before joining a trial is important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using intermittent pneumatic compression (IPC) combined with exercise for peripheral arterial disease (PAD) because it introduces a unique approach. Unlike typical treatments for PAD, which often involve medications like antiplatelets and statins or procedures such as angioplasty, IPC offers a non-invasive way to improve blood flow. The IPC device works by applying pressure to the legs, potentially enhancing circulation and supporting exercise therapy, which is crucial for managing PAD. Additionally, combining IPC with exercise could synergistically boost the benefits of physical activity, making it a promising complementary strategy for patients.

What evidence suggests that this trial's treatments could be effective for peripheral arterial disease?

Research has shown that intermittent pneumatic compression (IPC) can help individuals with peripheral arterial disease (PAD) walk more effectively. Studies have found that IPC boosts blood flow and eases PAD symptoms, such as pain during walking. In this trial, some participants will use IPC combined with exercise, which previous research found to be even more effective, allowing individuals to walk longer without discomfort. Another study demonstrated that IPC improved muscle function, making it easier for individuals to remain active. Overall, strong evidence supports that using IPC, especially with exercise, can enhance walking endurance in people with PAD. ^{6 7 8 9 10}

Who Is on the Research Team?

Mary McDermott, MD

Principal Investigator

Northwestern Universtiy

Are You a Good Fit for This Trial?

This trial is for individuals with Peripheral Artery Disease (PAD), confirmed by an ankle-brachial index (ABI) of ≤0.90, or other vascular/angiographic evidence. Exclusions include wheelchair users, BMI >45 kg/m2, significant visual impairment affecting walking, non-English speakers, recent amputees or clinical trial participants, certain cognitive impairments and severe medical conditions.

Inclusion Criteria

I have been diagnosed with PAD based on specific tests.

I have PAD, confirmed by an ABI test or other vascular or angiographic evidence.

Exclusion Criteria

I use a wheelchair for mobility.

You are already exercising regularly or have participated in exercise rehabilitation in the last three months.

Your Mini-Mental Status Examination (MMSE) score is less than 23, or you have dementia.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intermittent pneumatic compression and/or sham therapy, with or without exercise, for six months

6 months

Regular home-based sessions

Follow-up

Participants are monitored for changes in walking endurance and other health metrics after treatment

6 months

Follow-up assessments at 6 and 12 months

Long-term Follow-up

Participants are assessed for the persistence of treatment benefits and additional health outcomes

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Exercise
• Intermittent Pneumatic Compression

Trial Overview The INTERCEDE trial tests if intermittent pneumatic compression combined with walking exercise improves walking endurance in PAD patients over six months versus a sham device plus exercise. It also examines the lasting effects after treatment ends.

How Is the Trial Designed?

Group I: IPC + exercise Experimental Treatment 2 Interventions

Participants will be asked to wear the intermittent pneumatic compression device for up to three hours daily. They will be helped to engage in home-based walking exercise therapy.

Group II: IPC + "no exercise" control Experimental Treatment 2 Interventions

Participants will be asked to wear the intermittent pneumatic compression device for up to three hours daily. They will be asked to participate in an educational/informational intervention consisting of an attention control intervention

Group III: sham control + exercise Active Control 2 Interventions

Participants will be asked to wear a sham intermittent pneumatic compression device for up to three hours daily. The sham device inflates at the same frequency, but to a much lower systolic pressure, compared to the therapeutic pneumatic compression device. Participants in this group will be helped to engage in home-based walking exercise therapy.

Group IV: sham control + "no exercise" control Active Control 2 Interventions

Participants will be asked to wear a sham intermittent pneumatic compression device for up to three hours daily. The sham device inflates at the same frequency, but to a much lower systolic pressure, compared to the therapeutic pneumatic compression device. Participants will be asked to participate in an educational/informational intervention, designed as an attention control group.

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

Intermittent pneumatic foot compression (IPC(foot)) significantly increased popliteal artery blood flow in both normal individuals (by 111%) and patients with intermittent claudication (by 51%), indicating its potential efficacy in improving circulation.

The mechanism behind this increased blood flow appears to be the reduction of peripheral resistance, as evidenced by changes in pulsatility index and end diastolic velocity, suggesting that IPC(foot) could be beneficial for managing peripheral vascular disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of intermittent pneumatic foot compression on popliteal artery haemodynamics. Delis, KT., Labropoulos, N., Nicolaides, AN., et al.[2016]

Intermittent pneumatic compression (IPC) significantly enhances popliteal artery blood flow in both healthy individuals and patients with intermittent claudication, with the greatest increase observed when using simultaneous foot and calf compression (IPC(foot+calf)).

The study found that IPC(foot+calf) not only increased blood flow but also improved blood flow velocity and reduced pulsatility index, suggesting that peripheral vasodilation is the key mechanism behind this effect, highlighting its potential for treating peripheral vascular disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The acute effects of intermittent pneumatic foot versus calf versus simultaneous foot and calf compression on popliteal artery hemodynamics: a comparative study. Delis, KT., Nicolaides, AN., Labropoulos, N., et al.[2012]

The novel intermittent pneumatic compression (IPC) device (Gradient Pump) significantly increased foot oxygenation in patients with severe peripheral arterial disease (PAD), while the traditional sequential foot-calf device showed a decrease in oxygenation.

The Gradient Pump also led to significant improvements in haemodynamics, such as increased blood flow and velocity in the popliteal artery, and had higher patient compliance compared to the traditional device.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute oxygenation changes on ischemic foot of a novel intermittent pneumatic compression device and of an existing sequential device in severe peripheral arterial disease. Manfredini, F., Malagoni, AM., Felisatti, M., et al.[2021]

In a study of 37 patients with intermittent claudication, those using intermittent pneumatic foot compression (IPC(foot)) for 4.5 months saw a 146% increase in initial claudication distance and a 106% increase in absolute claudication distance, indicating significant improvement in walking ability.

IPC(foot) also led to substantial increases in ankle brachial indices and popliteal artery volume flow, suggesting enhanced blood flow and collateral circulation, with benefits persisting for at least 12 months after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving walking ability and ankle brachial pressure indices in symptomatic peripheral vascular disease with intermittent pneumatic foot compression: a prospective controlled study with one-year follow-up. Delis, KT., Nicolaides, AN., Wolfe, JH., et al.[2013]

Pediatric patients with congenital heart disease (CHD) demonstrated significantly lower flexibility compared to the general population, with a baseline sit-and-reach score of 24.3 cm versus the population norm, indicating a need for targeted interventions.

After a 60-day fitness program, flexibility in CHD patients improved to normal levels, suggesting that directed training can effectively enhance flexibility in this population, including those with a history of sternotomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Flexibility: A Hidden But Trainable Morbidity in Pediatric Patients with Congenital Heart Disease. Hansen, K., Curran, T., O'Neill, JA., et al.[2023]

In a study of 48 patients with adult congenital heart disease, peak oxygen consumption (pVO2) measured by smartwatches showed a strong correlation with pVO2 measured during cardiopulmonary exercise tests (CPET), indicating that smartwatches can effectively monitor exercise capacity in this population.

The changes in pVO2 over time were also well correlated between the smartwatch and CPET measurements, suggesting that smartwatches can reliably track improvements or declines in exercise capacity in patients with complex heart conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peak oxygen consumption by smartwatches compared with cardiopulmonary exercise test in complex congenital heart disease. Tran, T., Steiner, JM., Venkateswaran, A., et al.[2023]

A study involving 156 children aged 9-16 years with congenital heart disease showed significant seasonal variations in physical activity levels, with peaks in late spring and autumn and dips during winter and summer school holidays.

Using a commercial activity tracker (Fitbit), the study found that children consistently averaged below 12,000 steps per day throughout the year, highlighting the need for season-specific counseling to encourage physical activity in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Children with congenital heart disease exhibit seasonal variation in physical activity. Kuan, MTY., Voss, C., Lopez, J., et al.[2020]

Youth with congenital heart disease (CHD) often have reduced exercise capacity and lower quality of life, highlighting the need for effective exercise interventions, particularly home-based programs that can be monitored via telemedicine.

A new 12-week randomized crossover trial is being conducted to evaluate the effectiveness of a home-based high-intensity interval training program using a video game-linked cycle ergometer, which may provide better cardiorespiratory benefits compared to traditional moderate-intensity exercises.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploring the Promise of Telemedicine Exercise Interventions in Children and Adolescents With Congenital Heart Disease. Spence, C., Khoo, N., Mackie, A., et al.[2023]

The incremental shuttle walking test effectively stratifies mortality risk in patients with pulmonary arterial hypertension (PAH), with a significant reduction in 1-year mortality observed as walking distance increases, from 32% at ≤30 meters to 1% at ≥430 meters.

This study analyzed data from 1,847 PAH patients and established specific distance thresholds for risk categorization, which can be integrated into existing risk assessment tools, demonstrating the test's potential as a simple and effective alternative to traditional maximal exercise testing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maximal Exercise Testing Using the Incremental Shuttle Walking Test Can Be Used to Risk-Stratify Patients with Pulmonary Arterial Hypertension. Lewis, RA., Billings, CG., Hurdman, JA., et al.[2022]

Intermittent pneumatic compression (IPC) significantly enhances venous outflow in both healthy individuals and claudicants, with IPC targeting both the foot and calf (IPC(foot+calf)) showing the greatest improvement in blood flow.

Increasing the pressure from 120 mmHg to 180 mmHg in IPC applied to the foot only provided minimal additional benefits, indicating that the combination of foot and calf compression is the most effective method for improving leg inflow.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhancing venous outflow in the lower limb with intermittent pneumatic compression. A comparative haemodynamic analysis on the effect of foot vs. calf vs. foot and calf compression. Delis, KT., Slimani, G., Hafez, HM., et al.[2016]

The study involving 29 healthy volunteers demonstrated that using a portable intermittent pneumatic compression (IPC) device significantly increased tissue oxygenation (StO2), especially in a long-sitting position compared to chair-sitting, with a 12% higher StO2 level post-intervention.

The IPC device not only improved StO2 during the intervention but also maintained elevated levels for up to 15 minutes afterward, suggesting its potential effectiveness in enhancing tissue health and possibly reducing the risk of postoperative deep vein thrombosis (DVT) or inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Examination of a new mobile intermittent pneumatic compression device in healthy adults. Chohan, A., Abram, S., Parkes, A., et al.[2022]

Intermittent pneumatic compression (IPC) of both the foot and calf at pressures of 120-140 mmHg and a frequency of 3-4 impulses per minute significantly reduces venous pressure, which can enhance blood flow and improve walking ability in individuals with claudication.

The study found that a one-second delay between calf and foot compression was more effective than shorter delays, indicating that timing is crucial for maximizing the benefits of IPC in improving peripheral hemodynamics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimum intermittent pneumatic compression stimulus for lower-limb venous emptying. Delis, KT., Azizi, ZA., Stevens, RJ., et al.[2004]

Citations

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Intermittent pneumatic compression for the treatment of ... This study aimed to identify the role of intermittent pneumatic compression in treating peripheral arterial disease and to investigate the types of treatment ...

2. jvascsurg.org jvascsurg.org/article/S0741-5214(13)01694-7/fulltext

New insights into the physiologic basis for intermittent ... Summary of existing clinical trials examining the effects of intermittent pneumatic compression (IPC) treatment on peripheral arterial disease (PAD) outcomes.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03871075

Study Details | NCT03871075 | Intermittent Pneumatic ... The INTERCEDE randomized trial will establish whether six-months of intermittent pneumatic compression combined with walking exercise improves walking ...

4. magonlinelibrary.com magonlinelibrary.com/doi/full/10.12968/jowc.2023.32.Sup5.S25

Compression therapy in peripheral artery disease Several studies suggest that intermittent pneumatic compression (IPC) devices can be used to treat critical limb ischaemia in patients without surgical options.

5. sciencedirect.com sciencedirect.com/science/article/pii/S0741521413016947

New insights into the physiologic basis for intermittent ... Further, in a cohort of 171 CLI patients, Sultan et al reported a 94% limb salvage rate at a 3.5-year follow-up, and 63% of the patients were free from major ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3061490/

Exercise Rehabilitation in Peripheral Artery Disease Increased physical activity may translate to slower functional decline and potentially to reduced cardiovascular risk.,,. Limited controlled data are available ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10562863/

Exercise Therapy in the Management of Peripheral Arterial ... Uncontrolled PAD can lead to decreased QoL, debility, amputation, and death. Exercise therapy is a first-line treatment for PAD with proven benefit and minimal ...

8. ahajournals.org ahajournals.org/doi/10.1161/CIR.0000000000000623

Optimal Exercise Programs for Patients With Peripheral ... 6 months of unsupervised intermittent walking exercise was demonstrated to improve time walked to onset of pain and peak walking time (PWT).

9. jvascsurg.org jvascsurg.org/article/S0741-5214(14)01636-X/fulltext

Safety of supervised exercise therapy in patients with ... Focusing on the two major cardiac complications, an even lower event rate of one event in 41,362 patient-hours was calculated. These results are in line with a ...

10. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1062030322000516

Outcomes following supervised exercise and home-based ... A 12-week course of supervised exercise results in significantly greater walking distance outcomes (COD and PWD) than unmonitored home-based exercise.