Peripheral Arterial Disease
Conditions
Keywords
peripheral arterial disease, granulocyte macrophage colony stimulating factor, PAD, GM-CSF, sargramostim, leukine, treadmill exercise
Brief summary
The PROPEL study will test the hypothesis that GM-CSF combined with supervised treadmill exercise will significantly improve functional performance in patients with PAD more than GM-CSF alone or supervised treadmill exercise alone. In addition to identifying novel therapeutic options for patients with PAD, the current proposal is expected to identify mechanisms by which functional impairment is improved in patients with PAD.
Detailed description
Eight million men and women in the United States have lower extremity peripheral arterial disease (PAD). PAD is expected to be increasingly common as the population survives longer with chronic disease. Patients with PAD have greater functional impairment and faster functional decline compared to those without PAD. However, currently there are only two FDA approved medications for improving functional performance in patients with PAD. Furthermore, these FDA approved medications are only modestly beneficial for improving walking performance in patients with PAD. Preliminary evidence suggests that increasing circulating levels of CD34+ cells with granulocyte macrophage colony stimulating factor (GM-CSF) or other therapies may improve walking performance in patients with PAD. However, results of small clinical trials testing the ability of GM-CSF to improve walking performance in patients with PAD are mixed. The association of GM-CSF with improved walking performance in PAD is not definitively established. Preliminary data also suggest that lower extremity ischemia, induced during walking exercise, may increase circulating CD34+ cell levels, enhance homing of CD34+ cells to ischemic sites, and augment the ability of GMCSF to improve walking performance in PAD. However, it is currently unknown whether the combination of GM-CSF and supervised treadmill exercise significantly improve functional performance more than either therapy alone.
Interventions
BEHAVIORALSupervised Treadmill Exercise Therapy
Exercise intervention will be delivered three times weekly for 26 weeks. In the first week, participants will be asked to exercise 15 minutes per session (excluding rest periods). Walking exercise duration will be increased to 25 minutes minutes per session during week 2. Week 3 and 4 sessions will also be 25 minutes long, but the intensity will be increased either to produce leg symptoms or at a target rate of perceived exertion (RPE)of 12-14 on the Borg's 6-20 scale. For weeks 5-8, walking duration will be increased to 40 to 50 minutes while maintaining intensity. For weeks 9-26, exercise duration will continue to be 40 to 50 minutes but we will increase intensity up to a maximum of 4.0 miles per hour at 10% grade.
OTHERHealth education sessions (Control)
Participants randomized to the attention control group will attend weekly one-hour educational sessions at Northwestern University for six months. These educational 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, C-reactive protein, and hypertension. Sessions do not include information about exercise.
The dose of GM-CSF will be 250 ug/M\^2 subcutaneously three times weekly for two weeks.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Northwestern University
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
1. Participants with an ankle brachial index (ABI) ≤ 0.90 will be eligible for participation. 2. Participants with an ABI \> 0.90 but ≤ 1.00 who experience a 20% drop in ankle pressure after the heel-rise exercise will be eligible. 3. Participants with an ABI \> 0.90 who have medical record evidence of prior lower extremity revascularization and experience a 20% drop in ankle pressure after the heel-rise exercise will be eligible for inclusion. 4. Participants with an ABI \> 0.90 who have medical record evidence of a non-invasive vascular laboratory test result consistent with PAD. Note that a screen-positive test from Lifeline Screening is not sufficient for inclusion in the study.
Exclusion criteria
The following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Six-Minute Walk Performance at 12-week Follow-up | change from baseline to week 12 | 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 |
|---|---|---|
| Change in Maximal Treadmill Walking Time at 12-week Follow-up | change from baseline to week 12 | The Gardner graded treadmill exercise test is the standard, accepted treadmill protocol for measuring change in maximal treadmill walking time in response to interventions among PAD participants. In the Gardner exercise protocol, speed is maintained at 2.0 miles per hour (mph) and treadmill grade increases by 2.0% every two minutes. If patients cannot begin walking at 2.0 mph, treadmill speed is started at 0.50 mph and increased by 0.50 mph every 2 minutes until the participant reaches 2.0 mph, after which the treadmill grade is increased every two minutes. |
| Change in CD34_CD45lo at 12-week Follow-up | change from baseline to week 12 | Red blood cells are lysed twice with freshly prepared lysis buffer. Remaining cells are stained with LIVE/DEAD® Fixable Dead Cell Stains for 20 minutes at room temperature and Fc receptors are blocked by incubating with Fc receptor blocking reagent for 10 minutes at 4oC. Samples are then stained with the following antibody cocktail for 30 minutes at 4oC: CD34 VioBlue, CD133-APC , CD45 AlexaFluor 700, and CD31 (PECAM-1) APC-eFluor® 780. Stained samples are acquired using a BD LSRII and analyzed using Flowjo software. The outcome is the absolute change in the percentages of cells. |
| Change in Brachial Artery Flow-mediated Dilation (FMD) at 12-week Follow-up | change from baseline to week 12 | The brachial artery is imaged 5 to 9 cm above the antecubital fossa using a linear array vascular ultrasound transducer. Three video sequences are obtained. The first verifies the location and baseline hemodynamic state of the brachial artery. The second begins 20 seconds before cuff inflation and continues for 10 seconds after inflation. The third begins 15 seconds before cuff release and continues for 90 seconds after deflation. Brachial artery FMD is calculated as the percent change in brachial artery diameter at 60 seconds and at 90 seconds after the release of the cuff. |
| Change in CD34_CD45lo_CD31_ at 12-week Follow-up | change from baseline to week 12 | Red blood cells are lysed twice with freshly prepared lysis buffer. Remaining cells are stained with LIVE/DEAD® Fixable Dead Cell Stains for 20 minutes at room temperature and Fc receptors are blocked by incubating with Fc receptor blocking reagent for 10 minutes at 4oC. Samples are then stained with the following antibody cocktail for 30 minutes at 4oC: CD34 VioBlue, CD133-APC , CD45 AlexaFluor 700, and CD31 (PECAM-1) APC-eFluor® 780. Stained samples are acquired using a BD LSRII and analyzed using Flowjo software. The outcome is the absolute change in the percentages of cells. |
| Change in CD34_CD45lo_CD31_CD133_ at 12-week Follow-up | change from baseline to week 12 | Red blood cells are lysed twice with freshly prepared lysis buffer. Remaining cells are stained with LIVE/DEAD® Fixable Dead Cell Stains for 20 minutes at room temperature and Fc receptors are blocked by incubating with Fc receptor blocking reagent for 10 minutes at 4oC. Samples are then stained with the following antibody cocktail for 30 minutes at 4oC: CD34 VioBlue, CD133-APC , CD45 AlexaFluor 700, and CD31 (PECAM-1) APC-eFluor® 780. Stained samples are acquired using a BD LSRII and analyzed using Flowjo software. The outcome is the absolute change in the percentages of cells. |
| Change in CD34_CD45loCD133_ at 12-week Follow-up | change from baseline to week 12 | Red blood cells are lysed twice with freshly prepared lysis buffer. Remaining cells are stained with LIVE/DEAD® Fixable Dead Cell Stains for 20 minutes at room temperature and Fc receptors are blocked by incubating with Fc receptor blocking reagent for 10 minutes at 4oC. Samples are then stained with the following antibody cocktail for 30 minutes at 4oC: CD34 VioBlue, CD133-APC , CD45 AlexaFluor 700, and CD31 (PECAM-1) APC-eFluor® 780. Stained samples are acquired using a BD LSRII and analyzed using Flowjo software. The outcome is the absolute change in the percentages of cells. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| A: GM-CSF + Supervised Treadmill Exercise Therapy Supervised Treadmill Exercise Therapy: Exercise intervention will be delivered three times weekly for 26 weeks. In the first week, participants will be asked to exercise 15 minutes per session (excluding rest periods). Walking exercise duration will be increased to 25 minutes minutes per session during week 2. Week 3 and 4 sessions will also be 25 minutes long, but the intensity will be increased either to produce leg symptoms or at a target rate of perceived exertion (RPE)of 12-14 on the Borg's 6-20 scale. For weeks 5-8, walking duration will be increased to 40 to 50 minutes while maintaining intensity. For weeks 9-26, exercise duration will continue to be 40 to 50 minutes but we will increase intensity up to a maximum of 4.0 miles per hour at 10% grade.
granulocyte macrophage colony stimulating factor (GM-CSF): The dose of GM-CSF will be 250 ug/M\^2 subcutaneously three times weekly for two weeks. | 53 |
| B: GM-CSF + Attention Control Group Health education sessions (Control): Participants randomized to the attention control group will attend weekly one-hour educational sessions at Northwestern University for six months. These educational 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, C-reactive protein, and hypertension. Sessions do not include information about exercise.
granulocyte macrophage colony stimulating factor (GM-CSF): The dose of GM-CSF will be 250 ug/M\^2 subcutaneously three times weekly for two weeks. | 53 |
| C: Placebo + Supervised Exercise Therapy Supervised Treadmill Exercise Therapy: Exercise intervention will be delivered three times weekly for 26 weeks. In the first week, participants will be asked to exercise 15 minutes per session (excluding rest periods). Walking exercise duration will be increased to 25 minutes minutes per session during week 2. Week 3 and 4 sessions will also be 25 minutes long, but the intensity will be increased either to produce leg symptoms or at a target rate of perceived exertion (RPE)of 12-14 on the Borg's 6-20 scale. For weeks 5-8, walking duration will be increased to 40 to 50 minutes while maintaining intensity. For weeks 9-26, exercise duration will continue to be 40 to 50 minutes but we will increase intensity up to a maximum of 4.0 miles per hour at 10% grade. | 53 |
| D: Placebo + Attention Control Group Health education sessions (Control): Participants randomized to the attention control group will attend weekly one-hour educational sessions at Northwestern University for six months. These educational 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, C-reactive protein, and hypertension. Sessions do not include information about exercise. | 51 |
| Total | 210 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| 12-Week Follow-Up (Primary Endpoint) | Cancelled visit | 0 | 2 | 0 | 1 |
| 12-Week Follow-Up (Primary Endpoint) | Death | 1 | 0 | 0 | 0 |
| 12-Week Follow-Up (Primary Endpoint) | Lost to Follow-up | 0 | 0 | 0 | 2 |
| 26-Week Follow-Up | Death | 0 | 1 | 0 | 0 |
| 26-Week Follow-Up | Lost to Follow-up | 1 | 1 | 0 | 1 |
| 6-Week Follow-Up | Cancelled visit | 0 | 1 | 0 | 2 |
| 6-Week Follow-Up | Death | 1 | 0 | 0 | 0 |
| 6-Week Follow-Up | Lost to Follow-up | 2 | 1 | 3 | 2 |
Baseline characteristics
| Characteristic | B: GM-CSF + Attention Control Group | C: Placebo + Supervised Exercise Therapy | A: GM-CSF + Supervised Treadmill Exercise Therapy | D: Placebo + Attention Control Group | Total |
|---|---|---|---|---|---|
| Age, Continuous | 67.9 years STANDARD_DEVIATION 7.5 | 67.5 years STANDARD_DEVIATION 8.7 | 66.6 years STANDARD_DEVIATION 9.5 | 66.0 years STANDARD_DEVIATION 8.6 | 67.0 years STANDARD_DEVIATION 8.6 |
| Ankle-brachial index (ABI) | 0.71 ratio STANDARD_DEVIATION 0.17 | 0.69 ratio STANDARD_DEVIATION 0.19 | 0.70 ratio STANDARD_DEVIATION 0.2 | 0.69 ratio STANDARD_DEVIATION 0.19 | 0.70 ratio STANDARD_DEVIATION 0.19 |
| Body Mass Index (BMI) | 30.7 kg/m^2 STANDARD_DEVIATION 6.9 | 31.7 kg/m^2 STANDARD_DEVIATION 6 | 29.7 kg/m^2 STANDARD_DEVIATION 6.5 | 29.9 kg/m^2 STANDARD_DEVIATION 6.8 | 30.5 kg/m^2 STANDARD_DEVIATION 6.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 2 Participants | 3 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 51 Participants | 51 Participants | 51 Participants | 48 Participants | 201 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 35 Participants | 33 Participants | 35 Participants | 38 Participants | 141 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 16 Participants | 19 Participants | 18 Participants | 11 Participants | 64 Participants |
| Sex: Female, Male Female | 19 Participants | 23 Participants | 20 Participants | 20 Participants | 82 Participants |
| Sex: Female, Male Male | 34 Participants | 30 Participants | 33 Participants | 31 Participants | 128 Participants |
| Six-minute walk distance | 339.8 meters STANDARD_DEVIATION 101 | 338.7 meters STANDARD_DEVIATION 95.6 | 336.4 meters STANDARD_DEVIATION 109.5 | 339.1 meters STANDARD_DEVIATION 92 | 338.5 meters STANDARD_DEVIATION 99.1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 53 | 1 / 53 | 0 / 53 | 0 / 51 |
| other Total, other adverse events | 52 / 53 | 49 / 53 | 50 / 53 | 48 / 51 |
| serious Total, serious adverse events | 17 / 53 | 13 / 53 | 9 / 53 | 12 / 51 |
Outcome results
Primary
Change in Six-Minute Walk Performance at 12-week Follow-up
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 12
Population: Data were imputed for participants who were lost to follow-up or who canceled the visit. Variables used for imputation were age, ankle brachial index, body mass index, sex, race, smoking status, baseline outcome values, leg symptoms, and comorbidities. SAS procedure MI was used to obtain 20 imputed data sets.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| A: GM-CSF + Supervised Treadmill Exercise Therapy | Change in Six-Minute Walk Performance at 12-week Follow-up | 22.2 meters |
| B: GM-CSF + Attention Control Group | Change in Six-Minute Walk Performance at 12-week Follow-up | -6.4 meters |
| C: Placebo + Supervised Exercise Therapy | Change in Six-Minute Walk Performance at 12-week Follow-up | 28.5 meters |
| D: Placebo + Attention Control Group | Change in Six-Minute Walk Performance at 12-week Follow-up | -5.0 meters |
p-value: 0.05295% CI: [5.1, 52.3]t-test, 2 sided
p-value: 0.9195% CI: [-30.2, 17.6]t-test, 2 sided
p-value: 0.9195% CI: [-25.2, 22.4]t-test, 2 sided
p-value: 0.0295% CI: [9.4, 57.7]t-test, 2 sided
Secondary
Change in Brachial Artery Flow-mediated Dilation (FMD) at 12-week Follow-up
The brachial artery is imaged 5 to 9 cm above the antecubital fossa using a linear array vascular ultrasound transducer. Three video sequences are obtained. The first verifies the location and baseline hemodynamic state of the brachial artery. The second begins 20 seconds before cuff inflation and continues for 10 seconds after inflation. The third begins 15 seconds before cuff release and continues for 90 seconds after deflation. Brachial artery FMD is calculated as the percent change in brachial artery diameter at 60 seconds and at 90 seconds after the release of the cuff.
Time frame: change from baseline to week 12
Population: Data were imputed for participants who were lost to follow-up or who canceled the visit. Variables used for imputation were age, ankle brachial index, body mass index, sex, race, smoking status, baseline outcome values, leg symptoms, and comorbidities. SAS procedure MI was used to obtain 20 imputed data sets.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| A: GM-CSF + Supervised Treadmill Exercise Therapy | Change in Brachial Artery Flow-mediated Dilation (FMD) at 12-week Follow-up | -0.37 percent change |
| B: GM-CSF + Attention Control Group | Change in Brachial Artery Flow-mediated Dilation (FMD) at 12-week Follow-up | 0.10 percent change |
| C: Placebo + Supervised Exercise Therapy | Change in Brachial Artery Flow-mediated Dilation (FMD) at 12-week Follow-up | 0.14 percent change |
| D: Placebo + Attention Control Group | Change in Brachial Artery Flow-mediated Dilation (FMD) at 12-week Follow-up | -0.72 percent change |
p-value: 0.4995% CI: [-1.67, 0.44]Wilcoxon (Mann-Whitney)
p-value: 0.4995% CI: [-1.84, 0.51]Wilcoxon (Mann-Whitney)
p-value: 0.4995% CI: [-0.66, 1.38]Wilcoxon (Mann-Whitney)
p-value: 0.4995% CI: [-0.64, 1.59]Wilcoxon (Mann-Whitney)
Secondary
Change in CD34_CD45lo at 12-week Follow-up
Red blood cells are lysed twice with freshly prepared lysis buffer. Remaining cells are stained with LIVE/DEAD® Fixable Dead Cell Stains for 20 minutes at room temperature and Fc receptors are blocked by incubating with Fc receptor blocking reagent for 10 minutes at 4oC. Samples are then stained with the following antibody cocktail for 30 minutes at 4oC: CD34 VioBlue, CD133-APC , CD45 AlexaFluor 700, and CD31 (PECAM-1) APC-eFluor® 780. Stained samples are acquired using a BD LSRII and analyzed using Flowjo software. The outcome is the absolute change in the percentages of cells.
Time frame: change from baseline to week 12
Population: Note: It is pre-specified in the study protocol that investigators will determine whether a supervised treadmill exercise intervention alone (Group C) is associated with greater increases in CD34+ cells at 12-week follow-up, compared to Group D. Therefore, only group C and group D are included here.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| A: GM-CSF + Supervised Treadmill Exercise Therapy | Change in CD34_CD45lo at 12-week Follow-up | -0.002 percentage of cells |
| B: GM-CSF + Attention Control Group | Change in CD34_CD45lo at 12-week Follow-up | 0.004 percentage of cells |
p-value: 0.0995% CI: [-0.012, 0.001]t-test, 2 sided
Secondary
Change in CD34_CD45loCD133_ at 12-week Follow-up
Red blood cells are lysed twice with freshly prepared lysis buffer. Remaining cells are stained with LIVE/DEAD® Fixable Dead Cell Stains for 20 minutes at room temperature and Fc receptors are blocked by incubating with Fc receptor blocking reagent for 10 minutes at 4oC. Samples are then stained with the following antibody cocktail for 30 minutes at 4oC: CD34 VioBlue, CD133-APC , CD45 AlexaFluor 700, and CD31 (PECAM-1) APC-eFluor® 780. Stained samples are acquired using a BD LSRII and analyzed using Flowjo software. The outcome is the absolute change in the percentages of cells.
Time frame: change from baseline to week 12
Population: Note: It is pre-specified in the study protocol that investigators will determine whether a supervised treadmill exercise intervention alone (Group C) is associated with greater increases in CD34+ cells at 12-week follow-up, compared to Group D. Therefore, only group C and group D are included here.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| A: GM-CSF + Supervised Treadmill Exercise Therapy | Change in CD34_CD45loCD133_ at 12-week Follow-up | -0.002 percentage of cells |
| B: GM-CSF + Attention Control Group | Change in CD34_CD45loCD133_ at 12-week Follow-up | 0.004 percentage of cells |
p-value: 0.0395% CI: [-0.01, -0.001]t-test, 2 sided
Secondary
Change in CD34_CD45lo_CD31_ at 12-week Follow-up
Red blood cells are lysed twice with freshly prepared lysis buffer. Remaining cells are stained with LIVE/DEAD® Fixable Dead Cell Stains for 20 minutes at room temperature and Fc receptors are blocked by incubating with Fc receptor blocking reagent for 10 minutes at 4oC. Samples are then stained with the following antibody cocktail for 30 minutes at 4oC: CD34 VioBlue, CD133-APC , CD45 AlexaFluor 700, and CD31 (PECAM-1) APC-eFluor® 780. Stained samples are acquired using a BD LSRII and analyzed using Flowjo software. The outcome is the absolute change in the percentages of cells.
Time frame: change from baseline to week 12
Population: Note: It is pre-specified in the study protocol that investigators will determine whether a supervised treadmill exercise intervention alone (Group C) is associated with greater increases in CD34+ cells at 12-week follow-up, compared to Group D. Therefore, only group C and group D are included here.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| A: GM-CSF + Supervised Treadmill Exercise Therapy | Change in CD34_CD45lo_CD31_ at 12-week Follow-up | -0.003 percentage of cells |
| B: GM-CSF + Attention Control Group | Change in CD34_CD45lo_CD31_ at 12-week Follow-up | 0.002 percentage of cells |
p-value: 0.0995% CI: [-0.012, 0.001]t-test, 2 sided
Secondary
Change in CD34_CD45lo_CD31_CD133_ at 12-week Follow-up
Red blood cells are lysed twice with freshly prepared lysis buffer. Remaining cells are stained with LIVE/DEAD® Fixable Dead Cell Stains for 20 minutes at room temperature and Fc receptors are blocked by incubating with Fc receptor blocking reagent for 10 minutes at 4oC. Samples are then stained with the following antibody cocktail for 30 minutes at 4oC: CD34 VioBlue, CD133-APC , CD45 AlexaFluor 700, and CD31 (PECAM-1) APC-eFluor® 780. Stained samples are acquired using a BD LSRII and analyzed using Flowjo software. The outcome is the absolute change in the percentages of cells.
Time frame: change from baseline to week 12
Population: Note: It is pre-specified in the study protocol that investigators will determine whether a supervised treadmill exercise intervention alone (Group C) is associated with greater increases in CD34+ cells at 12-week follow-up, compared to Group D. Therefore, only group C and group D are included here.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| A: GM-CSF + Supervised Treadmill Exercise Therapy | Change in CD34_CD45lo_CD31_CD133_ at 12-week Follow-up | -0.003 percentage of cells |
| B: GM-CSF + Attention Control Group | Change in CD34_CD45lo_CD31_CD133_ at 12-week Follow-up | 0.001 percentage of cells |
p-value: 0.1795% CI: [-0.009, 0.002]t-test, 2 sided
Secondary
Change in Maximal Treadmill Walking Time at 12-week Follow-up
The Gardner graded treadmill exercise test is the standard, accepted treadmill protocol for measuring change in maximal treadmill walking time in response to interventions among PAD participants. In the Gardner exercise protocol, speed is maintained at 2.0 miles per hour (mph) and treadmill grade increases by 2.0% every two minutes. If patients cannot begin walking at 2.0 mph, treadmill speed is started at 0.50 mph and increased by 0.50 mph every 2 minutes until the participant reaches 2.0 mph, after which the treadmill grade is increased every two minutes.
Time frame: change from baseline to week 12
Population: Data were imputed for participants who were lost to follow-up or who canceled the visit. Variables used for imputation were age, ankle brachial index, body mass index, sex, race, smoking status, baseline outcome values, leg symptoms, and comorbidities. SAS procedure MI was used to obtain 20 imputed data sets.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| A: GM-CSF + Supervised Treadmill Exercise Therapy | Change in Maximal Treadmill Walking Time at 12-week Follow-up | 3.5 minutes |
| B: GM-CSF + Attention Control Group | Change in Maximal Treadmill Walking Time at 12-week Follow-up | -0.1 minutes |
| C: Placebo + Supervised Exercise Therapy | Change in Maximal Treadmill Walking Time at 12-week Follow-up | 4.2 minutes |
| D: Placebo + Attention Control Group | Change in Maximal Treadmill Walking Time at 12-week Follow-up | 0.5 minutes |
p-value: <0.0195% CI: [2.1, 5]t-test, 2 sided
p-value: 0.4495% CI: [-2.1, 0.8]t-test, 2 sided
p-value: 0.4495% CI: [-2.1, 0.9]t-test, 2 sided
p-value: <0.0195% CI: [2.2, 5.2]t-test, 2 sided