Exercise and Weight Loss to Improve Mobility Function in Veterans With PAD
Phase: NA
Conditions: Peripheral Arterial Disease
Sponsor: VA Office of Research and Development

Exercise and Weight Loss to Improve Mobility Function in Veterans With PAD 
NCT02607033 
Version 4/12/2023 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Principal Investigator: Odessa Addison, PT, DPT, PhD 
Sponsor or funding source: Department of Veterans Affairs 
 
Peripheral artery disease (PAD) affects an estimated 12 -15 million adults in the US and an 
estimated 20% of older Veterans. Those with PAD ambulate with slow gait and experience 
decreased leg strength, dysmobility, reduced quality of life, serious morbidity, and often 
premature death. It is estimated that over 60% of individuals with PAD are overweight or obese. 
While PAD itself worsens mobility, obesity adds a further functional burden to older adults with 
PAD. Individuals diagnosed with PAD, who are also obese typically claudicate 40% more 
quickly than non-obese individuals and take 20% longer to recover after claudication. Studies of 
older obese adults without PAD have demonstrated that the combination of exercise and weight 
loss is more effective at improving physical function and body composition than exercise alone. 
While these findings likely translate to older adults with PAD, this hypothesis has yet to be 
tested.  
This study is designed to determine whether weight loss and exercise (WL+EX) versus exercise 
( EX ) alone will improve mobility function (walking ability) to a greater extent than exercise 
alone, and determine the mechanisms underlying changes in mobility function. The 
investigators hypothesize that a combined intervention of weight loss and exercise (aerobic and 
restive) will result in greater improvements in mobility function through improved muscle 
perfusion and reduced muscle fat infiltration than exercise alone in obese Veterans with PAD. 
The aims of the study are as follows: 
 
Aim 1: To compare the effects of WL+EX vs EX on mobility function in obese Veterans with 
PAD. The primary outcome will be claudication onset time during a standardized treadmill test. 
Aim 2: To determine the intrinsic perfusion and muscle mechanism underlying changes in 
mobility function brought about by the interventions. The primary mechanistic outcome will be 
muscle perfusion.  
Experimental Design: 
Overview: This study is designed to determine whether WL+EX will improve mobility function to 
a greater extent than EX alone and determine the mechanisms underlying changes in mobility 
function. We will study men and postmenopausal women with PAD. Participants will be 
randomized to WL+EX or EX alone.  All individuals will be studied at baseline and after 6 
months of intervention.  
Eligibility criteria include:  
Inclusion Criteria:  
-BMI >25 kg/m2 
-ABI <.90 
-Able to participate in a supervised exercise program at the Baltimore VA  
-No current plan for surgical revascularization 
-Claudication or leg symptoms when walking 
 
 

Exclusion Criteria:  
-Unstable angina or a recent heart attack    
-Active cancer 
-Diagnosis of dementia on medical record.  
-Current foot or leg ulcers 
-Already exercise 2x/week or more by self-report  
 
Study Procedures:  
 
The experimental design of this study involves 5 phases completed over 6-7 months 
(Table 1). Phase 1 involves screening and enrollment. Phase 2 involves baseline testing.  
Volunteers then will be randomly assigned to EX + WL or Ex (control) (phase 3). Phase 4 
consists of 6 months of supervised exercise training. Phase 5 consist of post intervention final 
research testing.   
 
Table 1: Research Design  
 
Time Duration 
Research Activity  
Phase 1 
1-3 weeks 
Screening & Enrollment 
Phase 2 
1-3 weeks  
Baseline Testing  
Phase 3 
1 day 
Randomization 
Phase 4 
6 months 
EX + WL or EX  
Phase 5 
1-3 weeks 
Post Intervention testing  
 
Subject Screening and Enrollment (Phase 1): 
Based on our prior studies, a substantial proportion of potential participants will not qualify for 
the study (screen failures). Therefore, after written informed consent and HIPAA authorization is 
obtained, a history and physical exam will be performed to determine the presence of PAD and 
any contraindications to study participation. As part of this screening process individuals will 
complete 1) a six-minute walk test with ankle and brachial blood pressures taken before and 
after the test; and 2) a history and physical exam. If a subject has recently (within the past 3 
months) had a history and physical examination as part of another research study already linked 
to this study, we will use the results of the history and physical exam from the prior study to 
reduce participant burden. 
 
Baseline Testing (Phase 2):   
There may be certain circumstances in which the Principal Investigator or clinical investigative 
team may choose not to perform some of the research procedures described below. If this 
occurs, it will be noted in the participant research notes. Participants may also be requested 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. 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 if they can endure the pain 
(at which time the test will end). Heart rate and ECG are monitored continuously; arm and ankle 
blood pressure are monitored intermittently throughout the protocol using either auscultation or 
Doppler ultrasound. 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.).  
 
2. Strength Testing: A) Muscular strength (e.g., leg extension, leg press, and/or leg flexion) will 
be measured by 1-repetition maximum (1RM) testing on Keiser K-300 air powered machines, a 
Biodex strength testing system, or using hand-held strength testing devices. 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 may perform multiple trials (typically ~3-7) with a brief 
rest period between trials. B) Plantar and dorsiflexion will be measured using a hand-held 
dynamometer or a 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. 
 
3. 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, and the 6-minute walk. We will also administer questionnaires 
(attached) including the Walking Impairment Questionnaire (WIQ).  
 
4. 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. We will also measure body circumferences with a tape measure. 
 
 
Randomization (Phase 3): Participant are randomly assigned to either EX + WL or EX as 
described below.  
 
Interventions (Phase 4):  
Individuals will be randomly assigned to six months of supervised exercise in one of the 
interventions below  
 
1. Active Exercise Training: All participants who are in the exercise program will exercise for 
approximately 6 months, 3 times per week at VA exercise facilities. These exercise sessions will 
be supervised by exercise physiologists or trained staff. The aerobic exercise training program 
will include a warmup followed by 30-45 minutes of cumulative walking on a treadmill, around a 
track, or around their home if home exercise program is utilized. 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 or educate patient to do so if they are exercising at home. 
 
2. Active Exercise + Weight Loss: Participants with BMI>25kg/m2 may be assigned to a weight 
loss group. This group will also receive active exercise as described above for 6 months. These 
participants will be counseled to lose body weight to assess the additive effect of weight loss on 
study outcomes. These participants will be encouraged to attend weekly weight loss classes 
where they will receive instructions on how to implement a heart-healthy weight loss diet (250-
350 kcal reduction per day). If they are unable to participate in person, this may be done over 
the phone. During these sessions, participants will learn how to adjust their eating habits, record 
and weigh what they eat, read food labels to eat low calorie high nutritional value foods low in 
saturated fat and cholesterol and sugar, develop proper eating behavior at the dinner table, and 
by following the recommendations for the America Heart Association and including 
approximately 1g of high-quality protein per kilogram of body weight per day. Participants may 
be asked to use The ASA24 system (https://asa24.nci.nih.gov/) to collect 24-hour food recalls 
during baseline testing and the intervention to self-monitor progress and document adherence. 
National Cancer Institute (NCI) investigators created the free, web-based Automated Self-
Administered 24-hour Recall (ASA24) system to administered 24-hour recalls. The ASA24 
system consists of a Respondent Website, used to collect data from participants, and a 
Researcher Website for managing study logistics and access nutrient and food group data files. 
The coordinator or study dietician will log into the VA computer and access the website and 
subject specific food logs. These subjects may be asked to continue the intervention until at 
least 5-10% weight loss is achieved. 
 
Post Intervention testing (Phase 5): After six-months of the intervention, testing will be 
repeated as described in Phase 2.  
 
Statistical Analysis Plan:  
 
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 (EX + WL) and the active control (EX). 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.  
 
 
 
 
 
 
 
 
 
 
 
 
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