Clinical trial NCT03871075: Intermittent Pneumatic Compression With and Without Exercise to Improve Functioning in Peripheral Artery Disease
Official title: Intermittent Pneumatic Compression With and Without Exercise to Improve Functioning in Peripheral Artery Disease: The INTERCEDE TRIAL
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Peripheral Artery Disease
Keywords: peripheral arterial disease
Peripheral Artery Disease
PAD
exercise
Intermittent claudication
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2019-03-12
Enrollment: 230
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The INTERCEDE randomized trial will establish whether six-months of intermittent pneumatic compression combined with walking exercise improves walking endurance at six-month follow-up, compared to walking exercise + sham compression therapy, in people with lower extremity peripheral artery disease (PAD). The INTERCEDE trial will also determine whether intermittent pneumatic compression therapy improves walking endurance at 6-month follow-up, compared to a sham compression therapy. The trial will also determine whether benefits of intermittent pneumatic compression persist after intermittent pneumatic compression treatment is completed.

Detailed description: Walking exercise is first-line therapy for PAD. However, many PAD patients are unable or unwilling to exercise. Therefore, in people with PAD, the investigators will determine whether intermittent pneumatic compression augments the benefits of exercise and whether intermittent pneumatic compression alone improves walking performance compared to sham control. The investigators will conduct a randomized trial (2 x 2 factorial design) of 230 PAD participants randomized to one of four groups: Group A: intermittent pneumatic compression + exercise; Group B: intermittent pneumatic compression+ "no exercise" control; Group C: sham control + exercise; and Group D: sham control + "no exercise" control. The intermittent pneumatic compression and sham interventions will be delivered for six months. The primary outcome is change in six-minute walk distance at 6-month follow-up. In secondary aims, the investigators will determine whether the benefits of intermittent pneumatic compression persist even after intermittent pneumatic compression is discontinued and delineate mechanisms by which intermittent pneumatic compression affects walking performance, by measuring changes in MRI-measured calf muscle perfusion and physical activity. The investigators will determine whether intermittent pneumatic compression improves systemic endothelial function, by measuring changes in brachial artery flow-mediated dilation (FMD).

Eligibility criteria: Inclusion Criteria:

All participants will have PAD. PAD will be defined as follows: first, an ankle-brachial index (ABI) \< or = 0.90 at the baseline study visit is an inclusion criterion for PAD. Second, potential participants with an ABI \>0.90 who have vascular laboratory evidence of PAD. Vascular laboratory evidence consists of objective evidence of PAD, including toe brachial index (TBI) \< or = 0.70, Duplex measure showing 70% stenosis or greater, or ABI values \< 0.90. Abnormal waveforms or pulse volume recordings alone from a non-invasive vascular laboratory test will not be sufficient for enrollment. Third, potential participants with an ABI \>0.90 who have angiographic evidence of PAD consisting of a stenosis of 70% or greater in a lower extremity artery.

Exclusion Criteria:

1. Above- or below-knee amputation.
2. Critical limb ischemia or ABI \< 0.30 in the setting of ischemic symptoms at rest or physical examination findings consistent with critical limb ischemia. Some potential participants with symptoms or signs of critical limb ischemia may be excluded at the principal investigator's discretion if the ABI is 0.30 or higher.
3. Wheelchair-bound.
4. Current foot ulcer on bottom of foot.
5. Walking is primarily limited by a symptom other than PAD.
6. Failure to successfully complete the study run-in.
7. Major surgery, revascularization, or orthopedic surgery in the past 3 months or planned in the next 12 months.
8. Major medical illness including Parkinson's Disease, lung disease requiring oxygen, cancer requiring treatment in the previous two years, or life-threatening illness with a life expectancy of less than six months. Participants who only use oxygen at night will be potentially eligible. \[NOTE: potential participants treated for cancer in the past two years may still qualify if they have had treatment for early stage cancer in the past two years and the prognosis is excellent. Potential participants treated for basal cell or squamous cell skin cancer will not be excluded.\]
9. Already exercising at a level consistent with exercise intervention. Current or recent participation in exercise rehabilitation (within the past three months).
10. Recently diagnosed (within the past three months) with acute lower extremity deep venous thrombosis, pulmonary embolism, or severe heart failure (i.e. New York Heart Association (NYHA) Class III or IV).
11. Mini-Mental Status Examination (MMSE) score \<23 or dementia.
12. Participation in or completion of a clinical trial in the previous three months.
13. Non-English speaking.
14. Increase in angina in the past month, angina at rest, or abnormal baseline treadmill stress test. Potential participants may become eligible after an abnormal baseline treadmill stress test if they have evidence of an absence of coronary ischemia based on testing (such as a stress test with imaging or a coronary angiogram) from a test performed with their own physician and if they do not have symptoms of unstable angina. The evidence of absent coronary ischemia, based on an imaging stress test or coronary angiogram, must have been performed within the previous year.
15. Ongoing infection of the toes, foot, or lower extremity.
16. Potential participants who started on cilostazol within the last three months. They may be evaluated for eligibility once three months have passed since beginning cilostazol.
17. Significant peripheral edema, defined as 3+ or greater edema severity, as determined by the principal investigator.
18. BMI \>45 kg/M2
19. Significant visual impairment that interferes with walking.
20. In addition to the above criteria, investigator discretion will be used to determine if the trial is unsafe or not a good fit for the potential participant.

Primary outcomes:
measure: Six-minute walk distance (intermittent pneumatic compression therapy + exercise v. exercise only)
timeFrame: Baseline to 6-month follow-up
measure: Six-minute walk distance (intermittent pneumatic compression therapy alone (without exercise) vs. sham alone (without exercise)
timeFrame: Baseline to 6-month follow-up
Secondary outcomes:
measure: Six-minute walk distance (intermittent pneumatic compression therapy + exercise v. exercise only)
timeFrame: Baseline to 12-month follow-up
measure: Six-minute walk distance (IPC only v. sham only)
timeFrame: Baseline to 12-month follow-up
measure: Calf muscle perfusion (intermittent pneumatic compression therapy + exercise v. exercise only)
timeFrame: Baseline to 6-month follow-up
measure: Brachial artery FMD (intermittent pneumatic compression therapy + exercise v. exercise only)
timeFrame: Baseline to 6-month follow-up
measure: Physical Activity measured by Actigraph activity monitor (intermittent pneumatic compression therapy + exercise v. exercise only)
timeFrame: Baseline to 6-month follow-up
measure: Calf muscle perfusion (intermittent pneumatic compression therapy + exercise v. exercise only)
timeFrame: Baseline to 12-month follow-up
measure: Brachial artery FMD (intermittent pneumatic compression therapy + exercise v. exercise only)
timeFrame: Baseline to 12-month follow-up
measure: Physical Activity measured by Actigraph activity monitor (intermittent pneumatic compression therapy + exercise v. exercise only)
timeFrame: Baseline to 12-month follow-up
measure: Calf muscle perfusion (intermittent pneumatic compression therapy only v. sham only)
timeFrame: Baseline to 6-month follow-up
measure: Brachial artery FMD (intermittent pneumatic compression therapy only v. sham only)
timeFrame: Baseline to 6-month follow-up
measure: Physical Activity measured by Actigraph activity monitor (intermittent pneumatic compression therapy only v. sham only)
timeFrame: Baseline to 6-month follow-up
measure: Calf muscle perfusion (intermittent pneumatic compression therapy only v. sham only)
timeFrame: Baseline to 12-month follow-up
measure: Brachial artery FMD (intermittent pneumatic compression therapy only v. sham only)
timeFrame: Baseline to 12-month follow-up
measure: Physical Activity measured by Actigraph activity monitor (intermittent pneumatic compression therapy only v. sham only)
timeFrame: Baseline to 12-month follow-up
Other outcomes:
measure: Mitochondrial biogenesis (intermittent pneumatic compression therapy + exercise v. exercise only)
timeFrame: Baseline to 6-month follow-up
measure: Mitochondrial activity (intermittent pneumatic compression therapy + exercise v. exercise only)
timeFrame: Baseline to 6-month follow-up
measure: Vascular endothelial growth factor abundance (intermittent pneumatic compression therapy + exercise v. exercise only)
timeFrame: Baseline to 6-month follow-up
measure: Anti-oxidant enzyme activity (intermittent pneumatic compression therapy + exercise v. exercise only)
timeFrame: Baseline to 6-month follow-up
measure: Immunohistochemistry-measured mitochondrial activity (intermittent pneumatic compression therapy + exercise v. exercise only)
timeFrame: Baseline to 6-month follow-up
measure: Autophagy (intermittent pneumatic compression therapy + exercise v. exercise only)
timeFrame: Baseline to 6-month follow-up
measure: Capillary density (intermittent pneumatic compression therapy + exercise v. exercise only)
timeFrame: Baseline to 6-month follow-up
measure: Satellite cell content (intermittent pneumatic compression therapy + exercise v. exercise only)
timeFrame: Baseline to 6-month follow-up
measure: Mitochondrial biogenesis (intermittent pneumatic compression therapy only v. sham only)
timeFrame: Baseline to 6-month follow-up
measure: Mitochondrial activity (intermittent pneumatic compression therapy only v. sham only)
timeFrame: Baseline to 6-month follow-up
measure: Vascular endothelial growth factor abundance (intermittent pneumatic compression therapy only v. sham only)
timeFrame: Baseline to 6-month follow-up
measure: Anti-oxidant enzyme activity (intermittent pneumatic compression therapy only v. sham only)
timeFrame: Baseline to 6-month follow-up
measure: Immunohistochemistry-measured mitochondrial activity (intermittent pneumatic compression therapy only v. sham only)
timeFrame: Baseline to 6-month follow-up
measure: Autophagy (intermittent pneumatic compression therapy only v. sham only)
timeFrame: Baseline to 6-month follow-up
measure: Capillary density (intermittent pneumatic compression therapy only v. sham only)
timeFrame: Baseline to 6-month follow-up
measure: Satellite cell content (intermittent pneumatic compression therapy only v. sham only)
timeFrame: Baseline to 6-month follow-up
Locations:
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Detroit
country: United States
facility: Henry Ford Health
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
Study officials:
affiliation: Northwestern Universtiy
name: Mary McDermott, MD
role: PRINCIPAL_INVESTIGATOR
References: