Peripheral Arterial DiseasePROPELNCT01408901

Treadmill Exercise and GM-CSF Study to Improving Functioning in Peripheral Artery Disease (PAD)

A study testing Supervised Treadmill Exercise Therapy and granulocyte macrophage colony stimulating factor (GM-CSF) in people with Peripheral Arterial Disease, run by Northwestern University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Any age
Conditions the study is for: Peripheral Arterial Disease
What is being tested?: Supervised Treadmill Exercise Therapy and granulocyte macrophage colony stimulating factor (GM-CSF)
Type of treatment: Injection or infusion, Lifestyle or therapy programme
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 210 participants
Where: 1 siteUnited States
Study dates: Sep 2011to 15 Aug 2017
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Any age
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

Participants with an ankle brachial index (ABI) ≤ 0.90 will be eligible for participation.
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.
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.
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.

Who cannot join

The following exclusion criteria will be initially assessed by telephone:
Below or above-knee amputation.
Wheelchair confinement.
Use of a walking aid other than a cane (i.e. people using walkers).
Non-English speaking.
Significant hearing impairment.

Show all 36Show fewer

Significant visual impairment.
Diagnosis of Parkinson's disease.
Inability to return to the medical center at the required visit frequency (three times per week).
> Class II New York Heart Association heart failure or angina (symptoms at rest or with minimal exertion).
Any increase in angina pectoris symptoms during the previous 6 months or angina at rest.
Foot ulcer. (Participants with a foot ulcer will be excluded by telephone and/or during a baseline study visit).
Lower extremity revascularization in the last three months or major orthopedic surgery during the previous three months.
Myocardial infarction, stroke, or coronary artery bypass grafting during the previous 3 months.
Major medical illnesses including end stage renal disease requiring dialysis and chronic lung disease requiring oxygen, since these individuals may not be able to adhere to study requirements. Participants who only use oxygen at night may still qualify.
Potential participants who have received G-CSF, GM-CSF, or erythropoietin within the past year will be excluded because these interventions may influence study outcomes independently of the interventions.
Pre-menopausal women will be excluded because cyclic estrogen changes can influence progenitor cell levels.
Potential participants with diabetes and documented proliferative retinopathy will be excluded because GM-CSF may exacerbate this condition.
Potential participants with a history of myeloid malignancy will be excluded because GM-CSF may exacerbate these conditions.
Potential participants who have been treated for late stage cancer during the past three years, since GM-CSF may theoretically activate quiescent cancer cells.
Planned lower extremity revascularization within the next 6 months.
Current participation in another clinical trial. If a participant recently completed a clinical trial, at least three months must have passed before they can be considered for the PROPEL Trial. However, for a clinical trial of stem cell or gene therapy intervention, potential participants will be potentially eligible immediately after the final study visit of the stem cell or gene therapy clinical trial, so long as at least six months has passed since the participant received their final treatment in the stem cell or gene therapy intervention.
Walking for exercise at a level comparable to that targeted in our intervention.
Current participation in or completion of a cardiac rehabilitation program within the last six months.
The following exclusion criteria will be assessed at the time of the study visit or later:
Severe aortic stenosis identified by physical exam at the study visit.
Critical limb ischemia identified by physical exam at the study visit.
Coronary ischemia during exercise, defined as ST segment depression > 1 mm during the baseline exercise treadmill test, with or without associated chest discomfort, without a perfusion stress test demonstrating no reversible ischemia within the previous 3 months.
Left-bundle branch block or significant ST-T wave changes on the baseline ECG without a perfusion stress test demonstrating no reversible ischemia within the previous 3 months.
Stopping during the treadmill stress test for shortness of breath, chest pain, hip pain, knee pain, or another symptom that may not represent ischemic leg pain.
Stopping during the six-minute walk test for symptoms other than ischemic leg symptoms.
Foot ulcer identified at the study visit.
Mini-Mental Status Examination (MMSE) score < 23 or disabling psychiatric disease.
Failure to complete a study run-in period.
Walking impairment due to a cause other than PAD.
In addition to the exclusion criteria listed above, individuals thought to be poorly suited to the intervention (i.e. not a good fit) can be excluded at the discretion of the principal investigator.

Trial locations and contacts

1 site in 1 country.

United States1 site

Northwestern University Feinberg School of Medicine
Chicago, Illinois, 60611

Other trials in United States

About this study

Official title: PROgenitor Cell Release Plus Exercise to Improve functionaL Performance in PAD: The PROPEL Study

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.

Read the 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.

Conditions: Peripheral Arterial Disease
Being tested: Supervised Treadmill Exercise Therapy, Health education sessions (Control), granulocyte macrophage colony stimulating factor (GM-CSF)
Keywords: peripheral arterial disease, granulocyte macrophage colony stimulating factor, PAD, GM-CSF, sargramostim, leukine, treadmill exercise
Medical subject headings: Peripheral Arterial Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Supervised Treadmill Exercise TherapyBehavioural
Also called treadmill exercise
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.
Health education sessions (Control)Other
Also called attention control group
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)Drug
Also called sargramostim, leukine
The dose of GM-CSF will be 250 ug/M^2 subcutaneously three times weekly for two weeks.

Study groups in NCT01408901
Study group	Role	What they receive
A: GM-CSF + supervised treadmill exercise therapy	Experimental	Not described Receives: Behavioral: Supervised Treadmill Exercise Therapy; Drug: granulocyte macrophage colony stimulating factor (GM-CSF)
B: GM-CSF + attention control group	Active comparator	Not described Receives: Other: Health education sessions (Control); Drug: granulocyte macrophage colony stimulating factor (GM-CSF)
C: placebo + supervised exercise therapy	Active comparator	Not described Receives: Behavioral: Supervised Treadmill Exercise Therapy
D: placebo + attention control group	Placebo comparator	Not described Receives: Other: Health education sessions (Control)

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: change from baseline to week 12

Secondary outcomes (6)

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.
Measured: change from baseline to week 12
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.
Measured: change from baseline to week 12
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.
Measured: change from baseline to week 12
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.
Measured: change from baseline to week 12
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.
Measured: change from baseline to week 12
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.
Measured: change from baseline to week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 201115 Aug 2017

First posted3 Aug 2011 (estimated)
Study startSep 2011
Primary completion15 Aug 2017
Study completion15 Aug 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (13)Papers the sponsor has linked to this study.
Other trials for Peripheral Arterial DiseaseStudies of the same condition, open and under way.
More trials run by Northwestern UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Factorial
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 210 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01408901
Sponsor's protocol ID: STU00049675
Other IDs: R01HL107510
Acronym: PROPEL
Status last verified: Jan 2020
First submitted: 1 Aug 2011
Last updated: 21 Jan 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: No

Publications

Domanchuk K, Ferrucci L, Guralnik JM, Criqui MH, Tian L, Liu K, Losordo D, Stein J, Green D, Kibbe M, Zhao L, Annex B, Perlman H, Lloyd-Jones D, Pearce W, Taylor D, McDermott MM. Progenitor cell release plus exercise to improve functional performance in peripheral artery disease: the PROPEL Study. Contemp Clin Trials. 2013 Nov;36(2):502-9. doi: 10.1016/j.cct.2013.09.011. Epub 2013 Sep 27.
PubMed 24080099
Saber R, Liu K, Ferrucci L, Criqui MH, Zhao L, Tian L, Guralnik JM, Liao Y, Domanchuk K, Kibbe MR, Green D, Perlman H, McDermott MM. Ischemia-related changes in circulating stem and progenitor cells and associated clinical characteristics in peripheral artery disease. Vasc Med. 2015 Dec;20(6):534-43. doi: 10.1177/1358863X15600255. Epub 2015 Aug 31.
PubMed 26324152
McDermott MM, Guralnik JM, Criqui MH, Liu K, Kibbe MR, Ferrucci L. Six-minute walk is a better outcome measure than treadmill walking tests in therapeutic trials of patients with peripheral artery disease. Circulation. 2014 Jul 1;130(1):61-8. doi: 10.1161/CIRCULATIONAHA.114.007002. No abstract available.
PubMed 24982117
McDermott MM. Lower extremity manifestations of peripheral artery disease: the pathophysiologic and functional implications of leg ischemia. Circ Res. 2015 Apr 24;116(9):1540-50. doi: 10.1161/CIRCRESAHA.114.303517.
PubMed 25908727
McDermott MM, Ferrucci L, Tian L, Guralnik JM, Lloyd-Jones D, Kibbe MR, Polonsky TS, Domanchuk K, Stein JH, Zhao L, Taylor D, Skelly C, Pearce W, Perlman H, McCarthy W, Li L, Gao Y, Sufit R, Bloomfield CL, Criqui MH. Effect of Granulocyte-Macrophage Colony-Stimulating Factor With or Without Supervised Exercise on Walking Performance in Patients With Peripheral Artery Disease: The PROPEL Randomized Clinical Trial. JAMA. 2017 Dec 5;318(21):2089-2098. doi: 10.1001/jama.2017.17437.
PubMed 29141087
McDermott MM, Cetlin MD, Domanchuk KJ, Xu S, Whipple MO, Polonsky T, Criqui MH, Guralnik JM, Tian L, Zhao L, Ho KJ, Greenland P, Treat-Jacobson D. Community-based recruitment with ankle brachial index testing to identify peripheral artery disease participants for randomized clinical trials. Am Heart J. 2026 Oct;300:107450. doi: 10.1016/j.ahj.2026.107450. Epub 2026 Apr 24.
PubMed 42035974
McDermott MM, Zhang D, Zhao L, Polonsky T, Ferrucci L, Ho KJ, Kibbe MR, Guralnik JM, Criqui MH, Tian L. Duration of Supervised Exercise Necessary for Meaningful Improvement in Peripheral Artery Disease. J Am Heart Assoc. 2025 Sep 16;14(18):e040058. doi: 10.1161/JAHA.124.040058. Epub 2025 Sep 5.
PubMed 40913279
Hammond MM, Tian L, Zhao L, Zhang D, McDermott MM. Attendance at Supervised Exercise Sessions and Walking Outcomes in Peripheral Artery Disease: Results From 2 Randomized Clinical Trials. J Am Heart Assoc. 2022 Dec 20;11(24):e026136. doi: 10.1161/JAHA.122.026136. Epub 2022 Dec 19.
PubMed 36533626
McDermott MM, Tian L, Criqui MH, Ferrucci L, Greenland P, Guralnik JM, Kibbe MR, Li L, Sufit R, Zhao L, Polonsky TS. Perceived Versus Objective Change in Walking Ability in Peripheral Artery Disease: Results from 3 Randomized Clinical Trials of Exercise Therapy. J Am Heart Assoc. 2021 Jun 15;10(12):e017609. doi: 10.1161/JAHA.120.017609. Epub 2021 Jun 2.
PubMed 34075780
Patel K, Polonsky TS, Kibbe MR, Guralnik JM, Tian L, Ferrucci L, Criqui MH, Sufit R, Leeuwenburgh C, Zhang D, Zhao L, McDermott MM. Clinical characteristics and response to supervised exercise therapy of people with lower extremity peripheral artery disease. J Vasc Surg. 2021 Feb;73(2):608-625. doi: 10.1016/j.jvs.2020.04.498. Epub 2020 May 19.
PubMed 32416309
Kosmac K, Gonzalez-Freire M, McDermott MM, White SH, Walton RG, Sufit RL, Tian L, Li L, Kibbe MR, Criqui MH, Guralnik JM, S Polonsky T, Leeuwenburgh C, Ferrucci L, Peterson CA. Correlations of Calf Muscle Macrophage Content With Muscle Properties and Walking Performance in Peripheral Artery Disease. J Am Heart Assoc. 2020 May 18;9(10):e015929. doi: 10.1161/JAHA.118.015929. Epub 2020 May 9.
PubMed 32390569
McDermott MM, Polonsky TS, Guralnik JM, Ferrucci L, Tian L, Zhao L, Stein J, Domanchuk K, Criqui MH, Taylor DA, Li L, Kibbe MR. Racial Differences in the Effect of Granulocyte Macrophage Colony-Stimulating Factor on Improved Walking Distance in Peripheral Artery Disease: The PROPEL Randomized Clinical Trial. J Am Heart Assoc. 2019 Jan 22;8(2):e011001. doi: 10.1161/JAHA.118.011001.
PubMed 30661439
Berroug J, Korcarz CE, Mitchell CK, Weber JM, Tian L, McDermott MM, Stein JH. Brachial artery intima-media thickness and grayscale texture changes in patients with peripheral artery disease receiving supervised exercise training in the PROPEL randomized clinical trial. Vasc Med. 2019 Feb;24(1):12-22. doi: 10.1177/1358863X18804050. Epub 2018 Nov 12.
PubMed 30418100

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 21 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: PROgenitor Cell Release Plus Exercise to Improve functionaL Performance in PAD: The PROPEL Study
ClinicalTrials.gov ID: NCT01408901
Acronym / sponsor ID: PROPEL / STU00049675
Conditions: Peripheral Arterial Disease
Keywords: peripheral arterial disease, granulocyte macrophage colony stimulating factor, PAD, GM-CSF, sargramostim, leukine, treadmill exercise
Study type: Interventional
Recruitment status: Completed
Enrolment: 210 participants (actual)
Lead sponsor: Northwestern UniversityUniversity, hospital or other
Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
Study start: Sep 2011
Primary completion: 15 Aug 2017 (actual)
Study completion: 15 Aug 2017 (actual)
First posted: 3 Aug 2011 (estimated)
Results: Posted 10 Dec 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Factorial
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 4

Arm	Type	Receives
A: GM-CSF + supervised treadmill exercise therapy	Experimental	Behavioral: Supervised Treadmill Exercise Therapy, Drug: granulocyte macrophage colony stimulating factor (GM-CSF)
B: GM-CSF + attention control group	Active comparator	Other: Health education sessions (Control), Drug: granulocyte macrophage colony stimulating factor (GM-CSF)
C: placebo + supervised exercise therapy	Active comparator	Behavioral: Supervised Treadmill Exercise Therapy
D: placebo + attention control group	Placebo comparator	Other: Health education sessions (Control)

Who may qualify

Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (4 listed)

Participants with an ankle brachial index (ABI) ≤ 0.90 will be eligible for participation.
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.
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.
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.

Key exclusion criteria (36 listed)

Below or above-knee amputation.
Wheelchair confinement.
Use of a walking aid other than a cane (i.e. people using walkers).
Non-English speaking.
Significant hearing impairment.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Supervised Treadmill Exercise TherapyAlso: treadmill exerciseExercise 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.	Behavioural	A: GM-CSF + supervised treadmill exercise therapy, C: placebo + supervised exercise therapy
Health education sessions (Control)Also: attention control groupParticipants 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.	Other	B: GM-CSF + attention control group, D: placebo + attention control group
granulocyte macrophage colony stimulating factor (GM-CSF)Also: sargramostim, leukineThe dose of GM-CSF will be 250 ug/M^2 subcutaneously three times weekly for two weeks.	Drug	A: GM-CSF + supervised treadmill exercise therapy, B: GM-CSF + attention control group

Primary outcome

Change in Six-Minute Walk Performance at 12-week Follow-up
Time frame: 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.

6 secondary outcomes

Change in Brachial Artery Flow-mediated Dilation (FMD) at 12-week Follow-up
Time frame: change from baseline to week 12
Change in Maximal Treadmill Walking Time at 12-week Follow-up
Time frame: change from baseline to week 12
Change in CD34_CD45lo at 12-week Follow-up
Time frame: change from baseline to week 12
Change in CD34_CD45loCD133_ at 12-week Follow-up
Time frame: change from baseline to week 12
Change in CD34_CD45lo_CD31_ at 12-week Follow-up
Time frame: change from baseline to week 12
Change in CD34_CD45lo_CD31_CD133_ at 12-week Follow-up
Time frame: change from baseline to week 12

Results and safety

Results posted to the registry on 10 Dec 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
A: GM-CSF + Supervised Treadmill Exercise Therapy	53	50
B: GM-CSF + Attention Control Group	53	51
C: Placebo + Supervised Exercise Therapy	53	50
D: Placebo + Attention Control Group	51	47

Primary outcome: Change in Six-Minute Walk Performance at 12-week Follow-up

Time frame: change from baseline to week 12. Mean (95% Confidence Interval). Unit: meters

Measure	A: GM-CSF + Supervised Treadmill Exercise Therapy n = 51	B: GM-CSF + Attention Control Group n = 53	C: Placebo + Supervised Exercise Therapy n = 53	D: Placebo + Attention Control Group n = 51
Value	22.2 (5.4 to 39.0)	-6.4 (-23.0 to 10.1)	28.5 (11.7 to 45.4)	-5.0 (-22.3 to 12.2)

A: GM-CSF + Supervised Treadmill Exercise Therapy vs B: GM-CSF + Attention Control Group: Mean Difference (Final Values): 28.7 (95% CI 5.1 to 52.3), p = 0.052, t-test, 2 sided
A: GM-CSF + Supervised Treadmill Exercise Therapy vs C: Placebo + Supervised Exercise Therapy: Mean Difference (Final Values): -6.3 (95% CI -30.2 to 17.6), p = 0.91, t-test, 2 sided
B: GM-CSF + Attention Control Group vs D: Placebo + Attention Control Group: Mean Difference (Final Values): -1.4 (95% CI -25.2 to 22.4), p = 0.91, t-test, 2 sided

Population analysed: 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.

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse event data was collected between randomization and final 26-week follow-up.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
A: GM-CSF + Supervised Treadmill Exercise Therapy	17 of 53 (32.1%)	52 of 53 (98.1%)	2 of 53
B: GM-CSF + Attention Control Group	13 of 53 (24.5%)	49 of 53 (92.5%)	1 of 53
C: Placebo + Supervised Exercise Therapy	9 of 53 (17%)	50 of 53 (94.3%)	0 of 53
D: Placebo + Attention Control Group	12 of 51 (23.5%)	48 of 51 (94.1%)	0 of 51

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Jan 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 24080099Domanchuk K, Ferrucci L, Guralnik JM, Criqui MH, Tian L, Liu K, Losordo D, Stein J, Green D, Kibbe M, Zhao L, Annex B, Perlman H, Lloyd-Jones D, Pearce W, Taylor D, McDermott MM. Progenitor cell release plus exercise to improve functional performance in peripheral artery disease: the PROPEL Study. Contemp Clin Trials. 2013 Nov;36(2):502-9. doi: 10.1016/j.cct.2013.09.011. Epub 2013 Sep 27.
Background: PubMed 26324152Saber R, Liu K, Ferrucci L, Criqui MH, Zhao L, Tian L, Guralnik JM, Liao Y, Domanchuk K, Kibbe MR, Green D, Perlman H, McDermott MM. Ischemia-related changes in circulating stem and progenitor cells and associated clinical characteristics in peripheral artery disease. Vasc Med. 2015 Dec;20(6):534-43. doi: 10.1177/1358863X15600255. Epub 2015 Aug 31.
Background: PubMed 24982117McDermott MM, Guralnik JM, Criqui MH, Liu K, Kibbe MR, Ferrucci L. Six-minute walk is a better outcome measure than treadmill walking tests in therapeutic trials of patients with peripheral artery disease. Circulation. 2014 Jul 1;130(1):61-8. doi: 10.1161/CIRCULATIONAHA.114.007002. No abstract available.
Background: PubMed 25908727McDermott MM. Lower extremity manifestations of peripheral artery disease: the pathophysiologic and functional implications of leg ischemia. Circ Res. 2015 Apr 24;116(9):1540-50. doi: 10.1161/CIRCRESAHA.114.303517.
Results publication: PubMed 29141087McDermott MM, Ferrucci L, Tian L, Guralnik JM, Lloyd-Jones D, Kibbe MR, Polonsky TS, Domanchuk K, Stein JH, Zhao L, Taylor D, Skelly C, Pearce W, Perlman H, McCarthy W, Li L, Gao Y, Sufit R, Bloomfield CL, Criqui MH. Effect of Granulocyte-Macrophage Colony-Stimulating Factor With or Without Supervised Exercise on Walking Performance in Patients With Peripheral Artery Disease: The PROPEL Randomized Clinical Trial. JAMA. 2017 Dec 5;318(21):2089-2098. doi: 10.1001/jama.2017.17437.
Derived from this study: PubMed 42035974McDermott MM, Cetlin MD, Domanchuk KJ, Xu S, Whipple MO, Polonsky T, Criqui MH, Guralnik JM, Tian L, Zhao L, Ho KJ, Greenland P, Treat-Jacobson D. Community-based recruitment with ankle brachial index testing to identify peripheral artery disease participants for randomized clinical trials. Am Heart J. 2026 Oct;300:107450. doi: 10.1016/j.ahj.2026.107450. Epub 2026 Apr 24.
Derived from this study: PubMed 40913279McDermott MM, Zhang D, Zhao L, Polonsky T, Ferrucci L, Ho KJ, Kibbe MR, Guralnik JM, Criqui MH, Tian L. Duration of Supervised Exercise Necessary for Meaningful Improvement in Peripheral Artery Disease. J Am Heart Assoc. 2025 Sep 16;14(18):e040058. doi: 10.1161/JAHA.124.040058. Epub 2025 Sep 5.
Derived from this study: PubMed 36533626Hammond MM, Tian L, Zhao L, Zhang D, McDermott MM. Attendance at Supervised Exercise Sessions and Walking Outcomes in Peripheral Artery Disease: Results From 2 Randomized Clinical Trials. J Am Heart Assoc. 2022 Dec 20;11(24):e026136. doi: 10.1161/JAHA.122.026136. Epub 2022 Dec 19.
Derived from this study: PubMed 34075780McDermott MM, Tian L, Criqui MH, Ferrucci L, Greenland P, Guralnik JM, Kibbe MR, Li L, Sufit R, Zhao L, Polonsky TS. Perceived Versus Objective Change in Walking Ability in Peripheral Artery Disease: Results from 3 Randomized Clinical Trials of Exercise Therapy. J Am Heart Assoc. 2021 Jun 15;10(12):e017609. doi: 10.1161/JAHA.120.017609. Epub 2021 Jun 2.
Derived from this study: PubMed 32416309Patel K, Polonsky TS, Kibbe MR, Guralnik JM, Tian L, Ferrucci L, Criqui MH, Sufit R, Leeuwenburgh C, Zhang D, Zhao L, McDermott MM. Clinical characteristics and response to supervised exercise therapy of people with lower extremity peripheral artery disease. J Vasc Surg. 2021 Feb;73(2):608-625. doi: 10.1016/j.jvs.2020.04.498. Epub 2020 May 19.
Derived from this study: PubMed 32390569Kosmac K, Gonzalez-Freire M, McDermott MM, White SH, Walton RG, Sufit RL, Tian L, Li L, Kibbe MR, Criqui MH, Guralnik JM, S Polonsky T, Leeuwenburgh C, Ferrucci L, Peterson CA. Correlations of Calf Muscle Macrophage Content With Muscle Properties and Walking Performance in Peripheral Artery Disease. J Am Heart Assoc. 2020 May 18;9(10):e015929. doi: 10.1161/JAHA.118.015929. Epub 2020 May 9.
Derived from this study: PubMed 30661439McDermott MM, Polonsky TS, Guralnik JM, Ferrucci L, Tian L, Zhao L, Stein J, Domanchuk K, Criqui MH, Taylor DA, Li L, Kibbe MR. Racial Differences in the Effect of Granulocyte Macrophage Colony-Stimulating Factor on Improved Walking Distance in Peripheral Artery Disease: The PROPEL Randomized Clinical Trial. J Am Heart Assoc. 2019 Jan 22;8(2):e011001. doi: 10.1161/JAHA.118.011001.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Mary M McDermott, MD principal investigator

Northwestern University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Dec 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Six-Minute Walk Performance at 12-week Follow-up (time frame: change from baseline to week 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01408901, which also lists 13 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jan 2020.