Post-revascularization Rehabilitation to Improve Function in Veterans With PAD
Phase: NA
Conditions: Peripheral Arterial Disease, Intermittent Claudication
Sponsor: VA Office of Research and Development

 
 
 
 
Post-revascularization rehabilitation to improve function in Veterans with peripheral 
arterial disease (PAD) 
 
 
 
PI: Steven J. Prior, Ph.D. 
 
 
 
NCT 02607046 
 
 
 
Approval: March, 28, 2019 
 

Post-revascularization rehabilitation to improve function in Veterans with peripheral 
arterial disease (PAD) 
 
STUDY PROCEDURES: 
INTERVENTIONS 
1.  
Active Exercise Training: All participants who are in the exercise program will exercise 
for approximately 3 months, 3 times per week at the Baltimore VA Medical Center Annex, or the 
VA Medical Center. These exercise sessions will be supervised by exercise physiologists or 
trained staff. The aerobic exercise training program will include a warm up followed by 30-45 
minutes of cumulative walking on a treadmill or around a track. Individuals will initially begin 
walking for 10-15 minutes per exercise session (depending on tolerance) and will progress 
weekly until 30-45 minutes of cumulative walking has been achieved. For individuals who 
experience claudication pain, they will be asked to walk until the claudication pain reaches a 3 
on a 0-4 scale (0= no pain, 1 = onset of pain, 2 = moderate pain, 3 = intense pain, and 4 = 
maximal pain) after which they will rest. They will then be asked to walk again. This pattern of 
intermittent walking will be continued until the prescribed number of minutes of walking is met. 
Subjects will also be asked to walk at home on days they do not perform supervised exercise. 
Participants may also participate in strength training (ST) during the same session. This will 
consist of training of the knee extensors, knee flexors, plantar flexors and dorsiflexors. Subjects 
will perform approximately 1-3 sets of 4-15 repetitions for each exercise as tolerated. Training 
may be performed on Keiser K-300 air powered machines utilizing pneumatic resistance (Leg 
Extension Machine, Leg Curl Machine, Leg Press Machine) or with resistance bands or tubes. 
Each session of ST will take approximately 15-30 minutes. Blood pressure and heart rate will be 
assessed before and after each session. If the participant has type 2 diabetes and is on 
medications that may result in hypoglycemia, we will monitor blood glucose levels before and 
after exercise. 
 
2. Passive Exercise Training (NMES): Neuromuscular electrical stimulation (NMES) will be used 
to electrically induce contraction of the plantarflexors and dorsiflexors of both lower extremities. 
The protocol will employ an FDA cleared device for this purpose. NMES is routinely used in 
clinical care and has been used in other studies at UMB. Our specific protocol will require the 
application of NMES units on each lower extremity. Electrodes will be placed over the plantar 
and dorsiflexors of each leg. The stimulator’s parameters setting will be adjusted to elicit 
contraction while maintaining participant comfort. Stimulation will be provided for approximately 
15-30 minutes daily as tolerated by the participant. 
 
 
 
TESTING PROCEDURES: 
*Based on each subject’s schedule and availability, the Principal Investigator or clinical 
investigative team may choose not to perform every research procedure described below. If this 
occurs it will be noted in the participant research notes. Participants may also be asked to 
repeat one or more of the research tests should it be necessary due to a technical error in its 
performance and/or measurement, an inadequate sample is obtained for analysis, or there was 
an unforeseen problem with data collection. 
 
1. 
Blood Sampling: Blood plasma and/or serum will be used to measure cardio-metabolic 
and angiogenic factors (growth factors, inflammatory cytokines, cardio- metabolic risk factors, 
and markers of nutritional status). We may also measure endothelial progenitor cells, new 
hormones, inflammatory proteins and biomarkers as other technologies for measuring 
biomarkers of cardiovascular disease are identified. We will store plasma and serum and blood 

cells for analysis at a later time. These samples will be de-identified. Genetic testing will also be 
performed on blood samples. 
 
2. 
Treadmill Exercise Test: The tests described below will be supervised by staff clinicians 
with the assistance of CPR-trained study team members. Subjects will walk on a treadmill at 
approximately 2mph and grade is increased every 2 minutes until the subject cannot continue. 
Subjects will wear a mask with a mouthpiece that will collect expired air for measurement of 
ventilated gasses. Subjects are instructed to report the onset of claudication pain and then to 
walk as long as they can endure the pain (at which time the test will end). Heart rate and ECG 
are monitored continuously; arm and ankle blood pressure is monitored intermittently throughout 
the protocol using either auscultation or Doppler ultrasound. Cardiac output (PhysioFlow 
Enduro) and calf muscle oxygen saturation (Oxiplex TS near-infrared spectroscopy) may also 
be non-invasively measured during the test. Exercise tests may be stopped if the subjects 
indicate they are unable to continue or they experience any of the following: chest pain, 
dizziness, faintness, fatigue, pallor, cyanosis, cardiac arrhythmias or decompensation, or severe 
hyper-or hypotension (American College of Sports Medicine 2006.Guidelines for Exercise 
Testing and Prescription 7th ed.). Subjects may be asked to repeat this test while wearing a 
NMES unit. During Phase 3 & 5 this test will be performed twice. Once to establish any 
improvements in how long the patient can walk they will be asked to walk as long as possible. 
The second test will be submaximal and will be terminated when the patient reaches the same 
time and grade completed in a previous research testing phase. The submaximal test will be 
supervised by a CPR-trained exercise physiologist. 
 
3. 
Strength Testing: A) Muscular strength (leg extension, leg press, and/or leg flextion) will 
be measured by 1-repetition maximum (1RM) testing on Keiser K-300 air powered machines or 
a Biodex strength testing system. Participants will complete a brief, low-intensity warm-up prior 
to the test. Participants will be asked to perform exercises against a gradually increasing 
resistance after each successful exercise repetition until the maximal load is obtained. They will 
be perform multiple trials (typically ~3-7) with ~ 1 minute of rest between trials. B) Plantar and 
dorsiflexion will be measured using a hand-held dynamometer or with the Biodex strength 
testing system. Participants will be properly stabilized to ensure minimal movement artifacts. 
Additionally, verbal encouragement will be provided during task to encourage maximal volitional 
contraction. 
 
5. 
Functional Tests and Questionnaires: The physical performance tests include the 
Modified Physical Performance Test [standing balance, chair rise, book lift, put on and remove 
jacket, pick up a penny, turn 360 degrees, 50-foot walk, stair ascent/descent, self-selected gait 
speed (8-foot walk)], grip strength, balance, and the 6-minute walk. We will also administer 
questionnaires (attached) including the Walking Impairment Questionnaire (WIQ), SF-36, the 
Life Space Questionnaire, and the Vascular Quality of Life (VascuQoL). Participants may be 
asked to repeat these tests while participating in the intervention so that we may assess interim 
efficacy. 
 
6. 
Body Composition: Total and regional fat mass, lean tissue mass, % body fat, bone 
mineral content, and bone density will be determined by dual-energy x-ray absorptiometry 
(DXA). Computed tomography scans of the abdomen and leg are done to quantify regional fat 
and muscle distribution. The DXA and CT scans are performed by radiology technicians. [*DXA 
and CT scans will only be performed during post-revascularization testing (Phase 3) and 3-
month testing (Phase 5).] We will also measure body circumferences with a tape measure. 
  

7. 
Ultrasound Testing: This test may be performed before and after exercise. Doppler 
ultrasound non-invasively visualizes anatomic structures and determines intra- arterial blood 
flow. The test may be performed at the Vascular Laboratory at the University of Maryland 
Medical Center. Subjects will be positioned on a cushioned table and gel will be applied to their 
skin. An ultrasound transducer will be moved over the areas of the body being imaged. 
Contrast-enhanced ultrasonography will be employed to improve visualization. This involves the 
administration of stabilized microbubbles, an ultrasound contrast agent via a peripheral 
intravenous line. Participants will undergo the ultrasound testing before and after a walking on a 
treadmill for approximately 10 minutes. 
 
STATISTICAL ANALYSIS: 
We will use exploratory data analyses to review our data looking for extreme values which will 
be checked for transcription or other errors. Because our outcome measures will be measured 
multiple times, our intent is to use repeated measures ANOVA to compare outcome measures 
among treatment and control. However, as this is a pilot study designed to demonstrate proof of 
concept and to generate data with which to make accurate power calculations, we may initially 
analyze within-group changes using paired t-tests and among-group differences with 
independent samples t-tests.