Granulocyte-Macrophage Stimulating Factor in the Treatment of Peripheral Arterial Disease (GPAD-2)

This study has been completed.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Arshed A. Quyyumi, Emory University
ClinicalTrials.gov Identifier:
NCT01041417
First received: December 29, 2009
Last updated: December 12, 2014
Last verified: December 2014
  Purpose

Peripheral arterial disease is a common condition in older adults involving poor arterial circulation in the legs leading to leg pain and debility. The body's own circulating blood vessel stem cells may help to improve circulation. This study will test whether treatment with the drug granulocyte macrophage colony stimulating factor (GM-CSF) will improve symptoms and signs of peripheral arterial disease over placebo after four weeks of therapy. As well this study will examine whether improvements in blood vessel function can be observed. Finally, we will measure blood vessel function and stem cell levels in order to determine whether they can help to predict whether patients wither peripheral arterial disease will suffer further cardiovascular complications.


Condition Intervention Phase
Peripheral Arterial Disease
Drug: Granulocyte-Macrophage Stimulating Factor (GM-CSF)
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Granulocyte-Macrophage Stimulating Factor (GM-CSF) and Mobilization of Progenitor Cells in Peripheral Arterial Disease: A Phase II Randomized Study

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • Change in Peak Walking Time During Treadmill Exercise Tolerance Test From Baseline to 3 Months [ Time Frame: Baseline, 3 months ] [ Designated as safety issue: No ]
    Exercise Tolerance Test (ETT) was conducted using the Gardner protocol. Participants exercised on a treadmill, starting at 2.0 mph. The intensity of exercise (speed) was increased in grade of 2% every 2 minutes. Participants were asked to exercise until symptom limitation and the time measured in seconds from the ETT was used for data analysis.


Secondary Outcome Measures:
  • Change in Peak Walking Time During Treadmill Exercise Tolerance Test From Baseline to 6 Months [ Time Frame: Baseline, 6 months ] [ Designated as safety issue: No ]
    Exercise Tolerance Test (ETT) was conducted using the Gardner protocol. Participants exercised on a treadmill, starting at 2.0 mph. The intensity of exercise (speed) was increased in grade of 2% every 2 minutes. Participants were asked to exercise until symptom limitation and the time measured in seconds from the ETT was used for data analysis.

  • Change in Claudication Onset Time (COT) From Baseline to 3 Months [ Time Frame: Baseline, 3 months ] [ Designated as safety issue: No ]
    Claudication is pain, tired or weak feeling that occurs in the legs, usually during activity such as walking. The COT was measured as the time to onset of the participant's typical claudication as the maximum distance the patient could walk on the treadmill.

  • Change in Claudication Onset Time (COT) From Baseline to 6 Months [ Time Frame: Baseline, 6 months ] [ Designated as safety issue: No ]
    Claudication is pain, tired or weak feeling that occurs in the legs, usually during activity such as walking. The COT was measured as the time to onset of the participant's typical claudication as the maximum distance the patient could walk on the treadmill.

  • Change in Walking Distance Scores on Walking Impairment Questionnaire (WIQ) From Baseline to 3 Months [ Time Frame: Baseline, 3 months ] [ Designated as safety issue: No ]
    The WIQ quantifies walking difficulty on a 100-point scale, in which 0 indicates extreme difficulty and 100 indicates no difficulty with walking distance.

  • Change in Walking Distance Scores on Walking Impairment Questionnaire (WIQ) From Baseline to 6 Months [ Time Frame: Baseline, 6 months ] [ Designated as safety issue: No ]
    The WIQ quantifies walking difficulty on a 100-point scale, in which 0 indicates extreme difficulty and 100 indicates no difficulty with walking distance.

  • Change in Walking Speed Score on Walking Impairment Questionnaire (WIQ) From Baseline to 3 Months [ Time Frame: Baseline, 3 months ] [ Designated as safety issue: No ]
    The WIQ quantifies walking difficulty on a 100-point scale, in which 0 indicates extreme difficulty and 100 indicates no difficulty with walking speed.

  • Change in Walking Speed Score on Walking Impairment Questionnaire (WIQ) From Baseline to 6 Months [ Time Frame: Baseline, 6 months ] [ Designated as safety issue: No ]
    The WIQ quantifies walking difficulty on a 100-point scale, in which 0 indicates extreme difficulty and 100 indicates no difficulty with walking speed.

  • Change in Stair Climbing Score on Walking Impairment Questionnaire (WIQ) From Baseline to 3 Months [ Time Frame: Baseline, 3 months ] [ Designated as safety issue: No ]
    The WIQ quantifies walking difficulty on a 100-point scale, in which 0 indicates extreme difficulty and 100 indicates no difficulty with stair climbing elements.

  • Change in Stair Climbing Score on Walking Impairment Questionnaire (WIQ) From Baseline to 6 Months [ Time Frame: Baseline, 6 months ] [ Designated as safety issue: No ]
    The WIQ quantifies walking difficulty on a 100-point scale, in which 0 indicates extreme difficulty and 100 indicates no difficulty with stair climbing elements.

  • Change in Score on Physical Composite Score (PCS) Subscale of the Short Form 36 Health Survey (SF-36) From Baseline to 3 Months [ Time Frame: Baseline, 3 months ] [ Designated as safety issue: No ]
    The SF-36 is a standard quality of life instrument. The PCS represents the the physical burden on quality of life and is a summary of questions related to physical impact of a disease or condition (physical function, role physical, bodily pain, and general health). PCS is a summary measure derived from 8 scale score and the score ranges from 0-100; higher scores indicate better performance.

  • Change in Score on Physical Composite Score (PCS) Subscale of the Short Form 36 Health Survey (SF-36) From Baseline to 6 Months [ Time Frame: Baseline, 6 months ] [ Designated as safety issue: No ]
    The SF-36 is a standard quality of life instrument. The PCS represents the the physical burden on quality of life and is a summary of questions related to physical impact of a disease or condition (physical function, role physical, bodily pain, and general health). PCS is a summary measure derived from 8 scale score and the score ranges from 0-100; higher scores indicate better performance.

  • Change in Score on Mental Composite Score (MCS) Subscale of the Short Form 36 Health Survey (SF-36) From Baseline to 3 Months [ Time Frame: Baseline, 3 months ] [ Designated as safety issue: No ]
    The SF-36 is a standard quality of life instrument. The MCS represents the the mental burden on quality of life and is a summary of questions related to mental impact of a disease or condition (mental function, role emotional, vitality, and mental health). MCS is a summary measure derived from 8 scale score and the score ranges from 0-100; higher scores indicate better performance.

  • Change in Score on Mental Composite Score (MCS) Subscale of the Short Form 36 Health Survey (SF-36) From Baseline to 6 Months [ Time Frame: Baseline, 6 months ] [ Designated as safety issue: No ]
    The SF-36 is a standard quality of life instrument. The MCS represents the the mental burden on quality of life and is a summary of questions related to mental impact of a disease or condition (mental function, role emotional, vitality, and mental health). MCS is a summary measure derived from 8 scale score and the score ranges from 0-100; higher scores indicate better performance.

  • Change in Score on Physical Functioning Subscale of the Short Form 36 Health Survey (SF-36) From Baseline to 3 Months [ Time Frame: Baseline, 3 months ] [ Designated as safety issue: No ]
    The SF-36 is a standard quality of life instrument. The physical functioning represents limitations in physical activities because of health problems. Physical functioning is a summary measure derived from 8 scale scores and the score ranges from 0-100; higher scores indicate better performance.

  • Change in Score on Physical Functioning Subscale of the Short Form 36 Health Survey (SF-36) From Baseline to 6 Months [ Time Frame: Baseline, 6 months ] [ Designated as safety issue: No ]
    The SF-36 is a standard quality of life instrument. The physical functioning represents limitations in physical activities because of health problems. Physical functioning is a summary measure derived from 8 scale scores and the score ranges from 0-100; higher scores indicate better performance.


Enrollment: 159
Study Start Date: September 2009
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GM-CSF
Subjects will receive GM-CSF 500μg (Sargramostim (Leukine), Sanofi Aventis) by a self-administered subcutaneous injection thrice weekly on Monday, Wednesday, and Friday for four weeks
Drug: Granulocyte-Macrophage Stimulating Factor (GM-CSF)
500 micrograms of GM-CSF
Other Name: GM-CSF, Leukine
Placebo Comparator: Placebo
Subjects will receive a saline injection (placebo) by a self-administered subcutaneous injection thrice weekly on Monday, Wednesday, and Friday for four weeks
Drug: Placebo
Saline injection
Other Name: Placebo

Detailed Description:

Peripheral artery disease (PAD) affects more than 8 million Americans. Although exercise, smoking cessation, anti-platelet therapy, cilostazol, statins and revascularization are used to treat PAD, men and women with PAD have significantly greater functional impairment and fasterfunctional decline than those without PAD. Stem and progenitor cell (PC) therapy that promotes neoangiogenesis is an emerging treatment modality in PAD. Progenitor cells, particularly those of endothelial origin, are involved in vascular repair and regeneration. They originate primarily but not exclusively from the bone marrow, differentiate into endothelial and other vascular cells, and contribute to neovascularization during tissue repair by direct and paracrine mechanisms. Endogenous, pharmacologically-stimulated, and exogenous PCs contribute to re-endothelialization and neovascularization. Granulocyte colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF) stimulate mobilization of hematopoietic and other PCs from the bone marrow.In the murine hind limb ischemia model, GM-CSF administered by injection or by plasmid transfer augments circulating levels of PCs, increases capillary density, and promotes arteriogenesis.GM-CSF also augments neo-endothelialization of denuded arteries, promotes proliferation, differentiation and survival of hematopoietic cells, monocytes and macrophages.

  Eligibility

Ages Eligible for Study:   21 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 160 males or post-menopausal females between 21 and 80 years of age. Female subjects must be (a) post-menopausal, (b) surgically sterile or (c) use adequate birth control and have a negative pregnancy test within 3 days prior to administration of study drug and should not be breastfeeding.
  • Documented PAD (By Ankle-Brachial Indices or Angiographically)
  • Clinically stable (at least 2 months) history of intermittent claudication with no change in symptom severity in the 2 months prior to screening.
  • On stable statin therapy for previous 3 months.
  • Peak Walking Time (PWT) between 1 and 12 minutes on a standardized Gardner treadmill protocol.
  • A Doppler-derived ankle-brachial index (ABI) of < 0.85 in the symptomatic limb after 10 minutes of rest at screening. For subjects with an ABI of >1.3 (non-compressible arteries) a Toe-Brachial Index (TBI) of < 0.70 must be obtained for subject qualification, or if ABI is > 0.85 to 1.0 , and a reduction of 20% in ABI measured within 1 minute of treadmill testing.
  • On appropriate and stable medical therapy for atherosclerosis for at least 2 months.
  • Able to give informed consent.
  • Diabetics with a dilated eye exam excluding proliferative retinopathy in the previous 12 months.

Exclusion Criteria:

  • Recent or current active infections (treated with antibiotics).
  • Recent (3 months) change in statin therapy
  • Critical limb ischemia either chronic (category 3 and 4 of SVS classification) or acute ischemia manifested by rest pain, ulceration, or gangrene.
  • Lower extremity vascular surgery, angioplasty or lumbar sympathectomy within 3 months of enrollment.
  • Participation in a structured exercise treatment protocol within 3 months of enrollment.
  • Prior myeloid cancer.
  • Unstable angina, myocardial infarction, TIA, stroke or revascularization in the preceding 4 months.
  • Severe heart failure (Class III or IV), heart muscle disease or atrial fibrillation.
  • Limitation on exercise for symptoms other than intermittent claudication such as arthritis or dyspnea.
  • Uncontrolled diabetes mellitus (defined as HbA1c > 10.0).
  • Chronic renal disease (creatinine of >2.5 mg/dl) or hepatic disease (> 3 X elevations in AST and ALT).
  • Ophthalmologic conditions associated with a neo-vascular response.
  • Alcohol or drug abuse, or any other disease process that, in the opinion of the PI, will interfere with the ability of the patient to participate in the study.
  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: NCT01041417

Locations
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
Sponsors and Collaborators
Emory University
Investigators
Principal Investigator: Arshed Quyyumi, MD Emory University
  More Information

No publications provided by Emory University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Arshed A. Quyyumi, Professor, Emory University
ClinicalTrials.gov Identifier: NCT01041417     History of Changes
Other Study ID Numbers: IRB00030362, 1RC2HL101515-01
Study First Received: December 29, 2009
Results First Received: May 15, 2014
Last Updated: December 12, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Emory University:
claudication

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 August 02, 2015