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

NCT01408901 | Completed Results DMC

• 2 other identifiers: STU00049675R01HL107510
• Study Type: interventional
• Target: 210
• Locations: 1 country
• Sites: 1

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.

Conditions

Peripheral Arterial Disease

Keywords

peripheral arterial disease; granulocyte macrophage colony stimulating factor; PAD; GM-CSF; sargramostim; leukine; treadmill exercise

Outcome Measures

Primary Outcomes (1)

• 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.

  change from baseline to week 12

Secondary Outcomes (6)

• Change in Brachial Artery Flow-mediated Dilation (FMD) at 12-week Follow-up

  change from baseline to week 12

• Change in Maximal Treadmill Walking Time at 12-week Follow-up

  change from baseline to week 12

• Change in CD34_CD45lo at 12-week Follow-up

  change from baseline to week 12

• Change in CD34_CD45loCD133_ at 12-week Follow-up

  change from baseline to week 12

• Change in CD34_CD45lo_CD31_ at 12-week Follow-up

  change from baseline to week 12

Study Arms (4)

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)

Interventions

Supervised Treadmill Exercise Therapy BEHAVIORAL

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.

Also known as: treadmill exercise

A: GM-CSF + supervised treadmill exercise therapy; C: placebo + supervised exercise therapy

Health education sessions (Control) OTHER

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.

Also known as: attention control group

B: GM-CSF + attention control group; D: placebo + attention control group

granulocyte macrophage colony stimulating factor (GM-CSF) DRUG

The dose of GM-CSF will be 250 ug/M\^2 subcutaneously three times weekly for two weeks.

Also known as: sargramostim, leukine

A: GM-CSF + supervised treadmill exercise therapy; B: GM-CSF + attention control group

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Northwestern University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

Related Publications (12)

• 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.

  PMID: 24080099 BACKGROUND

• 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.

  PMID: 26324152 BACKGROUND

• 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.

  PMID: 24982117 BACKGROUND

• 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.

  PMID: 25908727 BACKGROUND

• 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.

  PMID: 29141087 RESULT

• 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.

  PMID: 40913279 DERIVED

• 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.

  PMID: 36533626 DERIVED

• 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.

  PMID: 34075780 DERIVED

• 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.

  PMID: 32416309 DERIVED

• 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.

  PMID: 32390569 DERIVED

• 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.

  PMID: 30661439 DERIVED

• 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.

  PMID: 30418100 DERIVED

MeSH Terms

Conditions

Peripheral Arterial Disease

Interventions

Granulocyte-Macrophage Colony-Stimulating Factor; sargramostim

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Mary McDermott MD
• Organization: Northwestern University

mdm608@northwestern.edu

312-503-6419

Study Officials

• Mary M McDermott, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine and Preventive Medicine at Northwestern University Feinberg School of Medicine

Study Record Dates

• First Submitted: August 1, 2011
• First Posted: August 3, 2011
• Study Start: September 1, 2011
• Primary Completion: August 15, 2017
• Study Completion: August 15, 2017
• Last Updated: January 21, 2020
• Results First Posted: December 10, 2019

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)