Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials
Trial record 14 of 131 for:    Peripheral Arterial Disease OR claudication OR peripheral vascular disease | Open Studies | NIH, U.S. Fed

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Northwestern University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Mary McDermott, Northwestern University
ClinicalTrials.gov Identifier:
NCT01408901
First received: August 1, 2011
Last updated: October 24, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention
Peripheral Arterial Disease
Behavioral: Supervised Treadmill Exercise Therapy
Other: Health education sessions (Control)
Drug: granulocyte macrophage colony stimulating factor (GM-CSF)

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: PROgenitor Cell Release Plus Exercise to Improve functionaL Performance in PAD: The PROPEL Study

Resource links provided by NLM:


Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • Change in Six-Minute Walk Performance at 12-week follow-up [ Time Frame: change from baseline to week 12 ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • Change in Brachial Artery Flow-mediated Dilation (FMD) at 12-week follow-up [ Time Frame: change from baseline to week 12 ] [ Designated as safety issue: No ]
    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 Maximal treadmill walking time at 12-week follow-up [ Time Frame: change from baseline to week 12 ] [ Designated as safety issue: No ]
    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+ cells at 12-week follow-up [ Time Frame: change from baseline to week 12 ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 240
Study Start Date: September 2011
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A: GM-CSF + supervised treadmill exercise therapy Behavioral: 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.
Other Name: treadmill exercise
Drug: 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.
Other Names:
  • sargramostim
  • leukine
Active Comparator: B: GM-CSF + attention control group Other: 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.
Other Name: attention control group
Drug: 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.
Other Names:
  • sargramostim
  • leukine
Active Comparator: C: placebo + supervised exercise therapy Behavioral: 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.
Other Name: treadmill exercise
Placebo Comparator: D: placebo + attention control group Other: 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.
Other Name: attention control group

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 based on abnormal toe pressures consistent with PAD will be eligible (toe pressure < 0.70 in either leg). Note that a screen-positive test from Lifeline Screening is not sufficient for inclusion in the study. Non-invasive vascular laboratory evidence of PAD must be obtained from an accredited vascular laboratory.

Exclusion Criteria:

The following exclusion criteria will be initially assessed by telephone:

  1. Below or above-knee amputation.
  2. Wheelchair confinement.
  3. Use of a walking aid other than a cane (i.e. people using walkers).
  4. Non-English speaking.
  5. Significant hearing impairment.
  6. Significant visual impairment.
  7. Diagnosis of Parkinson's disease.
  8. Inability to return to the medical center at the required visit frequency (three times per week).
  9. > Class II New York Heart Association heart failure or angina (symptoms at rest or with minimal exertion).
  10. Any increase in angina pectoris symptoms during the previous 6 months or angina at rest.
  11. Foot ulcer. (Participants with a foot ulcer will be excluded by telephone and/or during a baseline study visit).
  12. Lower extremity revascularization in the last nine months or major orthopedic surgery during the previous six months.
  13. Myocardial infarction, stroke, or coronary artery bypass grafting during the previous 3 months.
  14. 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.
  15. 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.
  16. Pre-menopausal women will be excluded because cyclic estrogen changes can influence progenitor cell levels.
  17. Potential participants with diabetes and documented proliferative retinopathy will be excluded because GM-CSF may exacerbate this condition.
  18. Potential participants with a history of myeloid malignancy will be excluded because GM-CSF may exacerbate these conditions.
  19. Potential participants who have been treated for late stage cancer during the past three years, since GM-CSF may theoretically activate quiescent cancer cells.
  20. Planned lower extremity revascularization within the next 6 months.
  21. 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, participants who have taken part in another exercise trial within the last year will be excluded until six months have passed since they completed the last exercise trial.
  22. Walking for exercise at a level comparable to that targeted in our intervention.
  23. 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:

  24. Severe aortic stenosis identified by physical exam at the study visit.
  25. Critical limb ischemia identified by physical exam at the study visit.
  26. 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.
  27. 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.
  28. 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.
  29. Stopping during the six-minute walk test for symptoms other than ischemic leg symptoms.
  30. Foot ulcer identified at the study visit.
  31. Mini-Mental Status Examination (MMSE) score < 23 or disabling psychiatric disease.
  32. Failure to complete a study run-in period.
  33. 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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01408901

Contacts
Contact: Kathryn Domanchuk, BS 312-503-6438 k-domanchuk@northwestern.edu

Locations
United States, Illinois
Northwestern University Feinberg School of Medicine Recruiting
Chicago, Illinois, United States, 60611
Contact: Kathryn Domanchuk, BS    312-503-6438    k-domanchuk@northwestern.edu   
Principal Investigator: Mary M McDermott, MD         
Sponsors and Collaborators
Northwestern University
Investigators
Principal Investigator: Mary M McDermott, MD Northwestern University
  More Information

No publications provided by Northwestern University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Mary McDermott, Professor of Medicine and Preventive Medicine at Northwestern University Feinberg School of Medicine, Northwestern University
ClinicalTrials.gov Identifier: NCT01408901     History of Changes
Other Study ID Numbers: STU00049675, R01HL107510
Study First Received: August 1, 2011
Last Updated: October 24, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Northwestern University:
peripheral arterial disease
granulocyte macrophage colony stimulating factor
PAD
GM-CSF
sargramostim
leukine
treadmill exercise

Additional relevant MeSH terms:
Peripheral Arterial Disease
Peripheral Vascular Diseases
Arterial Occlusive Diseases
Arteriosclerosis
Atherosclerosis
Cardiovascular Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on November 24, 2014