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

December 12, 2014 updated by: Arshed A. Quyyumi, Emory University

Granulocyte-Macrophage Stimulating Factor (GM-CSF) and Mobilization of Progenitor Cells in Peripheral Arterial Disease: A Phase II Randomized Study

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
159

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

21 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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 Names:
  • 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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in Peak Walking Time During Treadmill Exercise Tolerance Test From Baseline to 3 Months
Time Frame: Baseline, 3 months
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.
Baseline, 3 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in Peak Walking Time During Treadmill Exercise Tolerance Test From Baseline to 6 Months
Time Frame: Baseline, 6 months
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.
Baseline, 6 months
Change in Claudication Onset Time (COT) From Baseline to 3 Months
Time Frame: Baseline, 3 months
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.
Baseline, 3 months
Change in Claudication Onset Time (COT) From Baseline to 6 Months
Time Frame: Baseline, 6 months
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.
Baseline, 6 months
Change in Walking Distance Scores on Walking Impairment Questionnaire (WIQ) From Baseline to 3 Months
Time Frame: Baseline, 3 months
The WIQ quantifies walking difficulty on a 100-point scale, in which 0 indicates extreme difficulty and 100 indicates no difficulty with walking distance.
Baseline, 3 months
Change in Walking Distance Scores on Walking Impairment Questionnaire (WIQ) From Baseline to 6 Months
Time Frame: Baseline, 6 months
The WIQ quantifies walking difficulty on a 100-point scale, in which 0 indicates extreme difficulty and 100 indicates no difficulty with walking distance.
Baseline, 6 months
Change in Walking Speed Score on Walking Impairment Questionnaire (WIQ) From Baseline to 3 Months
Time Frame: Baseline, 3 months
The WIQ quantifies walking difficulty on a 100-point scale, in which 0 indicates extreme difficulty and 100 indicates no difficulty with walking speed.
Baseline, 3 months
Change in Walking Speed Score on Walking Impairment Questionnaire (WIQ) From Baseline to 6 Months
Time Frame: Baseline, 6 months
The WIQ quantifies walking difficulty on a 100-point scale, in which 0 indicates extreme difficulty and 100 indicates no difficulty with walking speed.
Baseline, 6 months
Change in Stair Climbing Score on Walking Impairment Questionnaire (WIQ) From Baseline to 3 Months
Time Frame: Baseline, 3 months
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.
Baseline, 3 months
Change in Stair Climbing Score on Walking Impairment Questionnaire (WIQ) From Baseline to 6 Months
Time Frame: Baseline, 6 months
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.
Baseline, 6 months
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
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.
Baseline, 3 months
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
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.
Baseline, 6 months
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
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.
Baseline, 3 months
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
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.
Baseline, 6 months
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
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.
Baseline, 3 months
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
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.
Baseline, 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Emory University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Heart, Lung, and Blood Institute (NHLBI)
National Institutes of Health (NIH)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2009

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 29, 2009

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 30, 2009

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 31, 2009

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 23, 2014

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 12, 2014

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRB00030362
  • 1RC2HL101515-01 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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