Peripheral Artery Disease
Conditions
Keywords
peripheral arterial disease, peripheral artery disease, PAD, exercise
Brief summary
This proposed study will determine whether a home-based exercise intervention that avoids continuous supervision and exercise-related ischemic pain improves walking performance at 52-week follow-up in people with PAD, compared to an attention control group and compared to a high intensity exercise intervention. In our secondary aims, we will determine whether high intensity exercise improves six-minute walk distance as compared to the attention control group. In secondary aims, we will also determine whether low intensity exercise and high intensity home-based exercise, respectively, improve patient reported outcomes, physical activity, and treadmill walking performance compared to attention control. Our intervention directly addresses two aspects of current practice guidelines that are major barriers to exercise for patients with PAD: 1) the recommendation for supervised exercise and 2) the recommendation for high intensity ischemic-pain inducing walking exercise.
Detailed description
We will randomize 305 PAD participants to one of three parallel arms: Group 1: Low-intensity, self-paced walking exercise; Group 2: Standard high intensity, ischemic pain-inducing walking exercise; Group 3: Non-exercising attention control group. The low and high intensity exercise groups will attend center-based exercise sessions once per week for four weeks followed by transition to an entirely home-based exercise program for an additional 48 weeks (52 weeks total). Coaches will contact participants weekly by telephone after the first four weeks of the intervention. The low and high intensity exercise interventions will use identical self-regulatory and support strategies. However, the low intensity exercise group will be instructed to exercise with minimal to no ischemic leg discomfort and the high intensity group will be instructed to exercise to maximal ischemic leg pain. These two distinct exercise prescriptions will be reinforced during 48 weeks of home-based exercise, using a well-validated behavioral coaching model that can be delivered by telephone once weekly. Our primary outcome is change in six-minute walk distance at 52-week follow-up. If our hypotheses are correct, millions of people with PAD will benefit from this alternative exercise regimen which will be accessible to most of the 8 million people in the U.S. who suffer from PAD.
Interventions
BEHAVIORALExercise
Participants in one of the exercise intervention groups will attend once weekly sessions at the medical center for the first four weeks of the study (Weeks 1-4, Phase I). During weeks 5-52 (Phase II), they will receive weekly telephone calls from a study coach.
OTHERAttention control
Our attention control group controls for the possibility that regular contact with the study team may improve outcomes in participants randomized to the intervention. Participants randomized to the control group will attend weekly one-hour educational sessions at Northwestern University for the first four weeks of the intervention (Phase I). These sessions are on topics of interest to the typical PAD patient and are led by physicians and other health care workers. Topics include Medicare Part D, nutritional supplements, and cancer screening. During Phase II (weeks 5-52), the attention control group will receive weekly telephone calls, lasting 5-15 minutes, with information on a health-related topic.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Northwestern University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Individuals collecting the outcome assessment will not be aware of group assignment.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
All participants will have PAD. PAD will be defined as follows. First, an ABI \< or = 0.90 at the baseline study visit is a well-accepted standard for the diagnosis of PAD and will be an inclusion criterion. Second, people with an ABI of \>0.90 and \< or = 1.00 who experience a 20% ankle systolic pressure drop after the heel-rise test will also be included. Third, potential participants with an ABI \> 0.90 who have vascular lab evidence of PAD or angiographic evidence of PAD who have ischemic symptoms during the six-minute walk and/or treadmill exercise stress test will be eligible. In addition to meeting a criterion for PAD, all participants must be symptomatic, defined by one of the following criteria:; a) ischemic leg symptoms (primarily assessed with the San Diego Claudication Questionnaire); b) report ischemic leg symptoms at the end of the six-minute walk; c) report ischemic leg symptoms at the end of the baseline treadmill stress test; d) walking impairment questionnaire results, e) interview with the potential participant about the presence and nature of leg symptoms during walking activity.
Exclusion criteria
1. Above or below knee amputation, critical limb ischemia, wheelchair confinement, or foot ulcer. 2. Individuals whose walking is limited by a condition other than PAD. 3. \> Class II NYHA heart failure or angina. Increase in angina, angina at rest, or abnormal baseline treadmill stress test. 4. Major surgery including lower extremity revascularization or orthopedic surgery during the prior three months or anticipated in the next twelve months. 5. Major medical illness including renal disease requiring dialysis, lung disease requiring oxygen other than at night, or cancer (other than non-melanoma skin cancer) requiring treatment in the prior three years. Potential participants may still qualify if they have had treatment for early stage cancer in the previous three years and the prognosis is excellent. 6. Mini-mental status examination score \<23, dementia, or psychiatric illness including severe depression or anxiety. Investigator discretion may be used to allow some people with an MMSE below 23 to participate if the investigator determines there is another reason for their lower score, including lack of sufficient familiarity with the English language or lack of sufficient education to achieve a score of 23 or higher. 7. Currently walking regularly for exercise at a level comparable to the amount of exercise prescribed in the intervention. 8. Current or recent (within 3 months) participation in another clinical trial or cardiac rehabilitation. For a clinical trial of a stem cell or gene therapy intervention, potential participants will be potentially eligible immediately after the final study visit for the clinical trial, so long as long as at least six months has passed since the participant received their final treatment in the stem cell or gene therapy intervention. For a clinical trial involving open-label therapy in which the treatment is not related to functional performance and will not change during the LITE Trial, participants may still qualify for the LITE Trial based on investigator discretion. 9. Individuals with PAD who have a history of lower extremity revascularization and have a normal ABI. 10. Individuals who are not able to walk for exercise at a sufficiently slow pace to avoid ischemic leg symptoms.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Six-minute Walk Distance | change from baseline to week 52 | In the six-minute walk, participants walk back and forth along a 100-ft hallway for six minutes after standardized instructions to complete as many laps as possible. Distance covered in six minutes is recorded. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximal Treadmill Walking Time | change from baseline to week 52 | In the treadmill walking test, participants walk on either a gardner or modified gardner protocol until they stop the test. Time walked is recorded |
| Physical Activity Levels | Change from baseline to week 52 | ActiGraph measured physical activity |
| Walking Impairment Questionnaire (WIQ) Distance and Speed Score. | change from baseline to week 52 | The WIQ is a well validated questionnaire that measures patient-reported walking limitations in distance and speed. |
| Health-related Quality of Life Measure | change from baseline to week 52 | The SF-36 physical functioning score will be used to measure quality of life. |
| Adherence to Intervention | from baseline to week 52 | Adherence is defined as the proportion achieving at least 80% of the prescribed exercise frequency and duration during the final month of the intervention. |
| Change in Muscle Biopsy Measures of Mitochondrial Oxidative Metabolism and Oxidative Stress. | change from baseline to week 52 | Muscle tissue will be collected at baseline and follow up to measures Change in muscle biopsy measures of mitochondrial oxidative metabolism and oxidative stress. |
| Six-minute Walk Distance | change from baseline to week 26 | In the six-minute walk, participants walk back and forth along a 100-ft hallway for six minutes after standardized instructions to complete as many laps as possible. Distance covered in six minutes is recorded. |
Other
| Measure | Time frame | Description |
|---|---|---|
| WIQ Distance and Speed Score | 26 week follow-up | The WIQ is a well validated questionnaire that measures patient-reported walking limitations in distance and speed. |
| Health Related Quality of Life | 26 weeks | SF-36 physical functioning score. |
| Adherence to Assigned Intervention | 26 weeks. | Adherence is defined as the proportion achieving at least 80% of the prescribed exercise frequency and duration during the final month of the intervention. |
| Physical Activity Levels Over Seven Days | 26 week follow-up. | ActiGraph |
| Qualitative Assessment | At 52 week follow up | We will use qualitative methods to explore participants' perceptions of the exercise interventions in the high and low-intensity exercise groups, respectively. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1 Low-intensity, self-paced walking exercise. Home based exercise.
Exercise: Participants in one of the exercise intervention groups will attend once weekly sessions at the medical center for the first four weeks of the study (Weeks 1-4, Phase I). During weeks 5-52 (Phase II), they will receive weekly telephone calls from a study coach. | 116 |
| Group 2 Standard high intensity, ischemic pain-inducing walking exercise. Home based exercise.
Exercise: Participants in one of the exercise intervention groups will attend once weekly sessions at the medical center for the first four weeks of the study (Weeks 1-4, Phase I). During weeks 5-52 (Phase II), they will receive weekly telephone calls from a study coach. | 124 |
| Group 3 Non-exercising attention control group. Contact with staff at same frequency as exercise groups, but staff deliver information on health not related to exercise.
Attention control: Our attention control group controls for the possibility that regular contact with the study team may improve outcomes in participants randomized to the intervention. Participants randomized to the control group will attend weekly one-hour educational sessions at Northwestern University for the first four weeks of the intervention (Phase I). These sessions are on topics of interest to the typical PAD patient and are led by physicians and other health care workers. Topics include Medicare Part D, nutritional supplements, and cancer screening. During Phase II (weeks 5-52), the attention control group will receive weekly telephone calls, lasting 5-15 minutes, with information on a health-related topic. | 65 |
| Total | 305 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 2 | 2 | 2 |
| Overall Study | Withdrawal by Subject | 18 | 16 | 15 |
Baseline characteristics
| Characteristic | Group 2 | Total | Group 3 | Group 1 |
|---|---|---|---|---|
| Age, Continuous | 68.8 years STANDARD_DEVIATION 8.7 | 69.3 years STANDARD_DEVIATION 9.5 | 69.5 years STANDARD_DEVIATION 10.1 | 69.8 years STANDARD_DEVIATION 10.1 |
| Ankle-brachial index | 0.67 ratio STANDARD_DEVIATION 0.15 | 0.66 ratio STANDARD_DEVIATION 0.16 | 0.67 ratio STANDARD_DEVIATION 0.15 | 0.66 ratio STANDARD_DEVIATION 0.17 |
| Body mass index | 31.1 kg/m^2 STANDARD_DEVIATION 7.3 | 30.7 kg/m^2 STANDARD_DEVIATION 7.1 | 30.8 kg/m^2 STANDARD_DEVIATION 7.3 | 30.3 kg/m^2 STANDARD_DEVIATION 6.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 6 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 81 Participants | 181 Participants | 35 Participants | 65 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 3 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 41 Participants | 114 Participants | 28 Participants | 45 Participants |
| Region of Enrollment United States | 124 participants | 305 participants | 65 participants | 116 participants |
| Sex: Female, Male Female | 60 Participants | 146 Participants | 32 Participants | 54 Participants |
| Sex: Female, Male Male | 64 Participants | 159 Participants | 33 Participants | 62 Participants |
| Six-min walk distance | 329 meters STANDARD_DEVIATION 101 | 328 meters STANDARD_DEVIATION 97 | 328 meters STANDARD_DEVIATION 87 | 326 meters STANDARD_DEVIATION 99 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 116 | 2 / 124 | 2 / 65 |
| other Total, other adverse events | 34 / 116 | 42 / 124 | 29 / 65 |
| serious Total, serious adverse events | 43 / 116 | 40 / 124 | 19 / 65 |
Outcome results
Primary
Six-minute Walk Distance
In the six-minute walk, participants walk back and forth along a 100-ft hallway for six minutes after standardized instructions to complete as many laps as possible. Distance covered in six minutes is recorded.
Time frame: change from baseline to week 52
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Group 1 | Six-minute Walk Distance | -6.4 meters |
| Group 2 | Six-minute Walk Distance | 34.5 meters |
| Group 3 | Six-minute Walk Distance | -15.1 meters |
Secondary
Adherence to Intervention
Adherence is defined as the proportion achieving at least 80% of the prescribed exercise frequency and duration during the final month of the intervention.
Time frame: from baseline to week 52
Secondary
Change in Muscle Biopsy Measures of Mitochondrial Oxidative Metabolism and Oxidative Stress.
Muscle tissue will be collected at baseline and follow up to measures Change in muscle biopsy measures of mitochondrial oxidative metabolism and oxidative stress.
Time frame: change from baseline to week 52
Secondary
Health-related Quality of Life Measure
The SF-36 physical functioning score will be used to measure quality of life.
Time frame: change from baseline to week 52
Secondary
Maximal Treadmill Walking Time
In the treadmill walking test, participants walk on either a gardner or modified gardner protocol until they stop the test. Time walked is recorded
Time frame: change from baseline to week 52
Secondary
Physical Activity Levels
ActiGraph measured physical activity
Time frame: Change from baseline to week 52
Secondary
Six-minute Walk Distance
In the six-minute walk, participants walk back and forth along a 100-ft hallway for six minutes after standardized instructions to complete as many laps as possible. Distance covered in six minutes is recorded.
Time frame: change from baseline to week 26
Secondary
Walking Impairment Questionnaire (WIQ) Distance and Speed Score.
The WIQ is a well validated questionnaire that measures patient-reported walking limitations in distance and speed.
Time frame: change from baseline to week 52
Other Pre-specified
Adherence to Assigned Intervention
Adherence is defined as the proportion achieving at least 80% of the prescribed exercise frequency and duration during the final month of the intervention.
Time frame: 26 weeks.
Other Pre-specified
Health Related Quality of Life
SF-36 physical functioning score.
Time frame: 26 weeks
Other Pre-specified
Physical Activity Levels Over Seven Days
ActiGraph
Time frame: 26 week follow-up.
Other Pre-specified
Qualitative Assessment
We will use qualitative methods to explore participants' perceptions of the exercise interventions in the high and low-intensity exercise groups, respectively.
Time frame: At 52 week follow up
Other Pre-specified
WIQ Distance and Speed Score
The WIQ is a well validated questionnaire that measures patient-reported walking limitations in distance and speed.
Time frame: 26 week follow-up