Peripheral Artery Disease (PAD)Phase 2GPAD-3NCT03304821
Granulocyte-Macrophage Stimulating Factor (GM-CSF) in Peripheral Arterial Disease
A Phase 2 study testing GM-CSF in people with Peripheral Artery Disease (PAD), run by Emory University at 1 site in United States.
Trial summary
Peripheral artery disease (PAD) is a disease in which plaque builds up in the arteries that carry blood to the head, organs, and limbs. PAD usually occurs in the arteries in the legs, but can affect any arteries. Read more about this study
- Who is it for?
- Ages 21 to 85 years
- Conditions the study is for
- Peripheral Artery Disease (PAD)
- What is being tested?
- GM-CSF
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 114 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Dec 2017to 5 Jul 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 21 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 symptomatic PAD
- Clinically stable (at least 2 months prior to enrollment) history of intermittent claudication or walking impairment (Rutherford Class II) with no change in symptom severity in the 2 months prior to screening.
- On statin therapy for previous 3 months prior to enrollment, unless statin intolerant.
- Peak Walking Time (PWT) between 1 and 12 minutes on a standardized Gardner treadmill protocol or modified Gardner protocol or less than 12 minutes on a modified Bruce protocol in case PWT on Gardner protocol is more than 12 minutes.
- A Doppler-derived ankle-brachial index (ABI) of < 0.90 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 > 0.9 to 1.0 , and a reduction of 20% in ABI measured within 1 minute of treadmill testing.
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- On appropriate and stable medical therapy for atherosclerosis for at least 2 months prior to enrollment.
- Able to give informed consent.
- Diabetics with a dilated eye exam excluding proliferative retinopathy in the previous 12 months prior to enrollment.
Who cannot join
- Recent or current active infections (treated with antibiotics)
- Recent (6 months prior to randomization) or current active cancer undergoing treatment
- Recent (3 months prior to randomization) change in statin or cilostazol therapy
- Critical limb ischemia either chronic (Rutherford Class >II) or acute ischemia manifested by rest pain, ulceration, or gangrene
- Recent (3 months prior to randomization) lower extremity vascular surgery, angioplasty or lumbar sympathectomy
- Planned participation in a structured exercise treatment protocol in the future or within period of study
Show all 23Show fewer
- Prior myeloid malignancy
- Recent (3 months prior to randomization) Unstable angina, myocardial infarction, transient ischemic attack (TIA), stroke or revascularization
- Severe heart failure (Class III or IV) or heart muscle disease
- Limitation on exercise for symptoms other than intermittent claudication such as arthritis or dyspnea
- Below- or above-knee amputation
- Wheelchair confinement
- Use of a walking aid other than a cane
- Walking impairment for reasons other than PAD e.g. Parkinson's disease
- Uncontrolled diabetes mellitus (defined as HbA1c > 10.0)
- Chronic renal disease (creatinine of >2.5 mg/dl) or hepatic disease (> 3 X elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT))
- White blood cell count < 3k/cmm
- Hemoglobin (HGB) < 10g/dL
- Blood Pressure Systolic >180 and/or Diastolic >100
- Taking Immunosuppressant drugs
- 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
- Inability to attend study visits
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Granulocyte-Macrophage Stimulating Factor (GM-CSF) in Peripheral Arterial Disease: The GPAD-3 Study
Peripheral artery disease (PAD) is a disease in which plaque builds up in the arteries that carry blood to the head, organs, and limbs. PAD usually occurs in the arteries in the legs, but can affect any arteries. Over time, plaque can harden and narrow the arteries which limits the flow of oxygen-rich blood to organs and other parts of the body. Blocked blood flow to the arteries can cause pain and numbness. The pain is usually worse with exercise and gets better with rest. PAD can raise the risk of getting an infection which could lead to tissue death and amputation. This study is investigating whether granulocyte-macrophage colony stimulating factor (GM-CSF) improves symptoms and blood flow in people with PAD. GM-CSF is a drug that is used to stimulate the bone marrow to release stem cells. Participants in the study will be randomly selected to receive GM-CSF or a placebo. After a four-week screening phase, participants will receive injections of GM-CSF or a placebo three times a week for three-weeks. Three months later, participants will again receive injections of GM-CSF or placebo three times a week for three-weeks. At six months, the study team will follow up to see if the group that received GM-CSF had more improvement than the group that received placebo.
Read the detailed description
Atherosclerotic peripheral artery disease (PAD) of the lower extremities afflicts up to 8% of the U.S. population and lack of adequate sustainable therapies necessarily results in severe morbidity and increased mortality. Both experimental and current clinical data indicate that GM-CSF has the capacity to mobilize a variety of progenitor cells (PCs), including endothelial PCs that appear to improve ischemia.
This study builds on the findings of prior research which showed improvements in claudication symptoms after treatment with GM-CSF. This study aims to answer whether repeat administration of GM-CSF at 3 months will further improve symptoms. The researchers will investigate in a double-blind placebo-controlled randomized study whether 3 weeks of three-times-a-week injection of GM-CSF will improve measures of ischemia in patients with intermittent claudication.
This study will recruit 176 participants with atherosclerotic PAD and claudication. After screening for inclusion and exclusion criteria, eligible subjects will be trained to perform subcutaneous injections and instructed to walk until they develop claudication or symptomatic limitation at least three times a day for 4 weeks. At the end of the 4-week period, subjects will undergo baseline testing and will be randomized to receive 500 μg/day of GM-CSF thrice weekly for 3 weeks (group A) or a placebo (group B). After 3 months, follow-up endpoint testing will be performed. Subjects in group A will then receive the second administration of 500 μg/day of subcutaneous GM-CSF thrice weekly for another 3 weeks and be followed for another 3 months for endpoint measurements, while Group B subjects will receive a matching placebo. The primary outcome is change in walking performance in the active treatment group after 6 months compared to the placebo group. The secondary outcome includes change in peak walking time at 6 months, changes in circulating progenitor cell levels, ankle brachial index (ABI), walking impairment questionnaire (WIQ) scores, and 36-item Short-Form Health Survey (SF-36) scores. Long-term follow up, by way of a telephone call, will occur with each participant one, two and three years after they enrolled in the study to administer questionnaires and collect adverse event data.
In response to the Coronavirus Disease 2019 (COVID-19) crisis on April 3, 2020 the Institutional Review Board (IRB) approved temporary modifications to this study to postpone study visits that do not involve active drug/placebo use.
- Conditions
- Peripheral Artery Disease (PAD)
- Being tested
- GM-CSF, Placebo
- Keywords
- Atherosclerotic peripheral artery disease, Granulocyte-macrophage colony stimulating factor (GM-CSF), Atherosclerosis, Cardiology, Vascular disease
- Medical subject headings
- Peripheral Arterial Disease, Atherosclerosis, Vascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GM-CSFDrug
Also called Sargramostim, Leukine
Participants will self-administer 500 μg/day of GM-CSF, subcutaneously, three times per week (Monday, Wednesday, Friday) for three weeks. After three months the participants will receive a second administration of 500 μg/day of subcutaneous GM-CSF, three times per week for another 3 weeks and then will be followed for another 3 months.
PlaceboDrug
Participants will self-administer 500 μg/day of a placebo, subcutaneously, three times per week (Monday, Wednesday, Friday) for three weeks. After three months the participants will receive a second administration of 500 μg/day of a placebo administered subcutaneously, three times per week for another 3 weeks and then will be followed for another 3 months.
| Study group | Role | What they receive |
|---|---|---|
| Granulocyte-macrophage Colony Stimulating Factor (GM-CSF) | Experimental | Participants receiving 500µg of granulocyte-macrophage colony stimulating factor (GM-CSF), administered subcutaneously. Prior to randomization to a study arm, eligible participants are trained to perform subcutaneous injections and instructed to walk at least three times a day until they develop claudication or symptomatic limitation for 4 weeks. Receives: Drug: GM-CSF |
| Placebo | Placebo comparator | Participants receiving 500µg of a placebo, administered subcutaneously. Prior to randomization to a study arm, eligible participants are trained to perform subcutaneous injections and instructed to walk at least three times a day until they develop claudication or symptomatic limitation for 4 weeks. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in 6-minute walk distance
Participants walk up and down a 100-foot hallway for 6 minutes to cover the maximum distance possible. The distance, measured in meters, completed after 6 minutes will be recorded. The primary outcome examines walking distance following two consecutive 3-monthly administrations of the study treatments.
Measured: Baseline, Month 6
Secondary outcomes (16)
Change in Peak Walking Time (PWT)
Graded treadmill exercise testing is performed using the Gardner protocol where the treadmill speed is kept at 2 mph and the grade starts at 0 and inclines by 2% every two minutes. The peak walking time (PWT) is the time (measured in seconds) until exercise is terminated because of severe claudication (pain in legs). Exercise testing is performed twice and longest time is used as the PWT for that study visit.
Measured: Baseline, Month 6
Change in Peak Walking Time (PWT) From First Through Second Treatment
To investigate whether there is further improvement with GM-CSF administered twice compared to a single administration, PWT at Month 6 compared to Month 3 is examined. Graded treadmill exercise testing is performed using the Gardner protocol where the treadmill speed is kept at 2 mph and the grade starts at 0 and inclines by 2% every two minutes. The peak walking time (PWT) is the time (in seconds) until exercise is terminated because of severe claudication (pain in legs). Exercise testing is performed twice and longest time is used as the PWT for that study visit.
Measured: Month 3, Month 6
Change in Peak Walking Time (PWT) After Single Treatment
To investigate whether there is improvement following a single treatment of GM-CSF, PWT at Month 3 compared to Baseline is examined. Graded treadmill exercise testing is performed using the Gardner protocol where the treadmill speed is kept at 2 mph and the grade starts at 0 and inclines by 2% every two minutes. The peak walking time (PWT) is the time (in seconds) until exercise is terminated because of severe claudication (pain in legs). Exercise testing is performed twice and longest time is used as the PWT for that study visit.
Measured: Baseline, Month 3
Change in 6-minute Walk Distance From First Through Second Treatment
To investigate whether there is further improvement with GM-CSF administered twice compared to a single administration, the examine walking distance at Month 6 compared to Month 3 is examined. Participants walk up and down a 100-foot hallway for 6 minutes to cover the maximum distance possible. The distance, measured in meters, completed after 6 minutes is recorded.
Measured: Month 3, Month 6
Change in 6-minute Walk Distance After Single Treatment
To investigate whether there is improvement following a single treatment of GM-CSF, the walking distance at Month 3 compared to Baseline is examined. Participants walk up and down a 100-foot hallway for 6 minutes to cover the maximum distance possible. The distance, measured in meters, completed after 6 minutes is recorded.
Measured: Baseline, Month 3
Change in Walking Impairment Questionnaire (WIQ): Walking Distance Score
The Walking Impairment Questionnaire (WIQ) domain of walking distance asks respondents to rate how difficult it is to walk around home, as well as distances of 50, 150, 300, 600, 900 and 1500 feet. Possible responses are: not hard (4), slightly difficult (3), somewhat difficult (2), very difficult (1), and unable to do (0). Total raw scores range from 0 to 28 with higher scores indicating increased ability to walk further distances.
Measured: Baseline, Month 3, Month 6, Month 9, Year 1
Change in Walking Impairment Questionnaire (WIQ): Walking Speed Score
The Walking Impairment Questionnaire (WIQ) domain of walking speed asks respondents to rate how difficult it is to walk the distance of one block slowly, at an average speed, quickly, and running/jogging. Possible responses are: not hard (4), slightly difficult (3), somewhat difficult (2), very difficult (1), and unable to do (0). Total raw scores range from 0 to 16 with higher scores indicating increased ability to walk fast.
Measured: Baseline, Month 3, Month 6, Month 9, Year 1
Change in Walking Impairment Questionnaire (WIQ): Stair Climbing Score
The Walking Impairment Questionnaire (WIQ) domain of stair climbing asks respondents to rate how difficult it is to climb 1, 2, and 3 flights of stairs. Possible responses are: not hard (4), slightly difficult (3), somewhat difficult (2), very difficult (1), and unable to do (0). Total raw scores range from 0 to 12 with higher scores indicating better ability to climb stairs.
Measured: Baseline, Month 3, Month 6, Month 9, Year 1
Change in 36-item Short-Form Health Survey (SF-36) Score
36-item Short-Form Health Survey (SF-36) consists of eight scaled scores for the domains of: vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health. The domains can be summarized to represent two distinct concepts for a Physical Component Summary (PCS) and a Mental Component Summary (MCS). Study participants respond to questions relating to their health and activity level by selecting from a variety of Likert scale and yes/no response options. Each scale is directly transformed into a 0-100 scale and lower scores indicate more disability (a score of 0 equates to maximum disability while a score of 100 indicates no disability). This study examines the Physical Component Summary (PCS) score as well as all domains.
Measured: Baseline, Month 3, Month 6, Month 9, Year 1
Change in Claudication Onset Time (COT)
Claudication onset time (COT) during the treadmill exercise will be recorded along with the peak walking time (PWT). The claudication onset time (COT) is the duration of exercise until onset of the participant's typical claudication. This is differentiated from the peak walking time (PWT) which is the time until exercise is terminated because of severe claudication. Graded treadmill exercise testing will be performed using the Gardner protocol where the treadmill speed is kept at 2 mph and the grade starts at 0 and inclines by 2% every two minutes.
Measured: Baseline, Month 3, Month 6, Month 9
Change in Ankle-Brachial Index (ABI)
To obtain the ankle-brachial index (ABI), bilateral upper and lower extremity blood pressure cuffs are inflated about 30 millimeters of mercury (mmHg) above the systolic pressure. Doppler flow signals are used to detect the reappearing perfusion while reducing the cuff pressure. The results is expressed as a segmental/arm pressure ratio (ABI index). The highest pressure of the two arms will be used for calculating the ABI. The average ratio is about 1.0+/-0.10; an index of 0.90 or lower is considered abnormal. In patients with calcific, non-compressible arteries (certain diabetics) where ABI measurements are unreliable, a toe/ arm pressure index ratio will be performed, with a 2.5 cm cuff used on the great or second toes. A toe/arm index less than 0.65 is considered abnormal.
Measured: Baseline, Month 3, Month 6, Month 9
Change in Foot Transcutaneous Oxygen Tension (TcPO2)
Foot transcutaneous oxygen tension (TcPO2) is a noninvasive way to measure peripheral arterial disease. TcPO2 is obtained with a monitor before exercise after the patients have been standing for three minutes and is monitored throughout exercise. Values are recorded at initial claudication distance, absolute claudication distance, and after recovery from exercise. A commonly used cut point is 60 millimeters of mercury (mmHg), with values below this indicating the presence of peripheral arterial disease.
Measured: Baseline, Month 3, Month 6, Month 9
Number of Circulating Mononuclear Cells Expressing CD34
The number of circulating mononuclear cells expressing the PC specific epitopes CD34 is counted using fluorescent activated sorting (FACS).
Measured: Baseline, Week 3, Month 3, Week 15, Month 6, Month 9
Number of Circulating Mononuclear Cells Expressing CD133
The number of circulating mononuclear cells expressing the PC specific epitopes CD133 is counted using fluorescent activated sorting (FACS).
Measured: Baseline, Week 3, Month 3, Week 15, Month 6, Month 9
Number of Circulating Mononuclear Cells Expressing VEGF2R (KDR)
The number of circulating mononuclear cells expressing the PC specific epitopes VEGF2R (KDR) is counted using fluorescent activated sorting (FACS).
Measured: Baseline, Week 3, Month 3, Week 15, Month 6, Month 9
Number of Circulating Mononuclear Cells Expressing CXCR4
The number of circulating mononuclear cells expressing the PC specific epitopes CXCR4 is counted using fluorescent activated sorting (FACS).
Measured: Baseline, Week 3, Month 3, Week 15, Month 6, Month 9
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2017
- Study start19 Dec 2017
- Primary completion5 Jul 2025
- Study completion5 Jul 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Peripheral Artery Disease (PAD)Studies of the same condition, open and under way.
- More trials run by Emory 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomized, in a 2:1 manner, to receive: * Group A: Subcutaneous GM-CSF 500µg on Monday, Wednesday, Friday (n=117) * Group B: Placebo on Monday, Wednesday, Friday (n=59) Participants will be stratified on diabetes status ensuring that a proportionate number of diabetics (2:1) are randomized to each group.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 114 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Arshed A. Quyyumi, Emory University
- Investigators
- Arshed Quyyumi, MD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03304821
- Sponsor's protocol ID
- IRB00087198
- Other IDs
- 1R61HL138657, 2025P011130
- Acronym
- GPAD-3
- Status last verified
- Aug 2026
- First submitted
- 4 Oct 2017
- Last updated
- 12 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Mehta A, Mavromatis K, Ko YA, Rogers SC, Dhindsa DS, Goodwin C, Patel R, Martini MA, Prasad M, Mokhtari A, Hesaroieh IG, Frohwein SC, Kutner MH, Harzand A, Wells BJ, Duwayri Y, Alabi O, Rajani RR, Brewster LP, Waller EK, Quyyumi AA. Rationale and design of the granulocyte-macrophage colony stimulating factor in peripheral arterial disease (GPAD-3) study. Contemp Clin Trials. 2020 Apr;91:105975. doi: 10.1016/j.cct.2020.105975. Epub 2020 Mar 4.
PubMed 32145440
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Granulocyte-Macrophage Stimulating Factor (GM-CSF) in Peripheral Arterial Disease: The GPAD-3 Study
- ClinicalTrials.gov ID
- NCT03304821
- Acronym / sponsor ID
- GPAD-3 / IRB00087198
- Conditions
- Peripheral Artery Disease (PAD)
- Keywords
- Atherosclerotic peripheral artery disease, Granulocyte-macrophage colony stimulating factor (GM-CSF), Atherosclerosis, Cardiology, Vascular disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 114 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 19 Dec 2017 (actual)
- Primary completion
- 5 Jul 2025 (actual)
- Study completion
- 5 Jul 2025 (actual)
- First posted
- 9 Oct 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Peripheral artery disease (PAD) is a disease in which plaque builds up in the arteries that carry blood to the head, organs, and limbs. PAD usually occurs in the arteries in the legs, but can affect any arteries. Over time, plaque can harden and narrow the arteries which limits the flow of oxygen-rich blood to organs and other parts of the body. Blocked blood flow to the arteries can cause pain and numbness. The pain is usually worse with exercise and gets better with rest. PAD can raise the risk of getting an infection which could lead to tissue death and amputation. This study is investigating whether granulocyte-macrophage colony stimulating factor (GM-CSF) improves symptoms and blood flow in people with PAD. GM-CSF is a drug that is used to stimulate the bone marrow to release stem cells. Participants in the study will be randomly selected to receive GM-CSF or a placebo. After a four-week screening phase, participants will receive injections of GM-CSF or a placebo three times a week for three-weeks. Three months later, participants will again receive injections of GM-CSF or placebo three times a week for three-weeks. At six months, the study team will follow up to see if the group that received GM-CSF had more improvement than the group that received placebo.
Detailed description
Atherosclerotic peripheral artery disease (PAD) of the lower extremities afflicts up to 8% of the U.S. population and lack of adequate sustainable therapies necessarily results in severe morbidity and increased mortality. Both experimental and current clinical data indicate that GM-CSF has the capacity to mobilize a variety of progenitor cells (PCs), including endothelial PCs that appear to improve ischemia.
This study builds on the findings of prior research which showed improvements in claudication symptoms after treatment with GM-CSF. This study aims to answer whether repeat administration of GM-CSF at 3 months will further improve symptoms. The researchers will investigate in a double-blind placebo-controlled randomized study whether 3 weeks of three-times-a-week injection of GM-CSF will improve measures of ischemia in patients with intermittent claudication.
This study will recruit 176 participants with atherosclerotic PAD and claudication. After screening for inclusion and exclusion criteria, eligible subjects will be trained to perform subcutaneous injections and instructed to walk until they develop claudication or symptomatic limitation at least three times a day for 4 weeks. At the end of the 4-week period, subjects will undergo baseline testing and will be randomized to receive 500 μg/day of GM-CSF thrice weekly for 3 weeks (group A) or a placebo (group B). After 3 months, follow-up endpoint testing will be performed. Subjects in group A will then receive the second administration of 500 μg/day of subcutaneous GM-CSF thrice weekly for another 3 weeks and be followed for another 3 months for endpoint measurements, while Group B subjects will receive a matching placebo. The primary outcome is change in walking performance in the active treatment group after 6 months compared to the placebo group. The secondary outcome includes change in peak walking time at 6 months, changes in circulating progenitor cell levels, ankle brachial index (ABI), walking impairment questionnaire (WIQ) scores, and 36-item Short-Form Health Survey (SF-36) scores. Long-term follow up, by way of a telephone call, will occur with each participant one, two and three years after they enrolled in the study to administer questionnaires and collect adverse event data.
In response to the Coronavirus Disease 2019 (COVID-19) crisis on April 3, 2020 the Institutional Review Board (IRB) approved temporary modifications to this study to postpone study visits that do not involve active drug/placebo use.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Participants will be randomized, in a 2:1 manner, to receive: * Group A: Subcutaneous GM-CSF 500µg on Monday, Wednesday, Friday (n=117) * Group B: Placebo on Monday, Wednesday, Friday (n=59) Participants will be stratified on diabetes status ensuring that a proportionate number of diabetics (2:1) are randomized to each group.
| Arm | Type | Receives |
|---|---|---|
| Granulocyte-macrophage Colony Stimulating Factor (GM-CSF) | Experimental | Drug: GM-CSFParticipants receiving 500µg of granulocyte-macrophage colony stimulating factor (GM-CSF), administered subcutaneously. Prior to randomization to a study arm, eligible participants are trained to perform subcutaneous injections and instructed to walk at least three times a day until they develop claudication or symptomatic limitation for 4 weeks. |
| Placebo | Placebo comparator | Drug: PlaceboParticipants receiving 500µg of a placebo, administered subcutaneously. Prior to randomization to a study arm, eligible participants are trained to perform subcutaneous injections and instructed to walk at least three times a day until they develop claudication or symptomatic limitation for 4 weeks. |
Who may qualify
- Ages
- 21 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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 symptomatic PAD
- Clinically stable (at least 2 months prior to enrollment) history of intermittent claudication or walking impairment (Rutherford Class II) with no change in symptom severity in the 2 months prior to screening.
- On statin therapy for previous 3 months prior to enrollment, unless statin intolerant.
- Peak Walking Time (PWT) between 1 and 12 minutes on a standardized Gardner treadmill protocol or modified Gardner protocol or less than 12 minutes on a modified Bruce protocol in case PWT on Gardner protocol is more than 12 minutes.
Key exclusion criteria (23 listed)
- Recent or current active infections (treated with antibiotics)
- Recent (6 months prior to randomization) or current active cancer undergoing treatment
- Recent (3 months prior to randomization) change in statin or cilostazol therapy
- Critical limb ischemia either chronic (Rutherford Class >II) or acute ischemia manifested by rest pain, ulceration, or gangrene
- Recent (3 months prior to randomization) lower extremity vascular surgery, angioplasty or lumbar sympathectomy
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 |
|---|---|---|
| GM-CSFAlso: Sargramostim, LeukineParticipants will self-administer 500 μg/day of GM-CSF, subcutaneously, three times per week (Monday, Wednesday, Friday) for three weeks. After three months the participants will receive a second administration of 500 μg/day of subcutaneous GM-CSF, three times per week for another 3 weeks and then will be followed for another 3 months. | Drug | Granulocyte-macrophage Colony Stimulating Factor (GM-CSF) |
| PlaceboParticipants will self-administer 500 μg/day of a placebo, subcutaneously, three times per week (Monday, Wednesday, Friday) for three weeks. After three months the participants will receive a second administration of 500 μg/day of a placebo administered subcutaneously, three times per week for another 3 weeks and then will be followed for another 3 months. | Drug | Placebo |
Primary outcome
Change in 6-minute walk distance
Time frame: Baseline, Month 6
Participants walk up and down a 100-foot hallway for 6 minutes to cover the maximum distance possible. The distance, measured in meters, completed after 6 minutes will be recorded. The primary outcome examines walking distance following two consecutive 3-monthly administrations of the study treatments.
16 secondary outcomes
Change in Peak Walking Time (PWT)
Time frame: Baseline, Month 6
Change in Peak Walking Time (PWT) From First Through Second Treatment
Time frame: Month 3, Month 6
Change in Peak Walking Time (PWT) After Single Treatment
Time frame: Baseline, Month 3
Change in 6-minute Walk Distance From First Through Second Treatment
Time frame: Month 3, Month 6
Change in 6-minute Walk Distance After Single Treatment
Time frame: Baseline, Month 3
Change in Walking Impairment Questionnaire (WIQ): Walking Distance Score
Time frame: Baseline, Month 3, Month 6, Month 9, Year 1
Change in Walking Impairment Questionnaire (WIQ): Walking Speed Score
Time frame: Baseline, Month 3, Month 6, Month 9, Year 1
Change in Walking Impairment Questionnaire (WIQ): Stair Climbing Score
Time frame: Baseline, Month 3, Month 6, Month 9, Year 1
Change in 36-item Short-Form Health Survey (SF-36) Score
Time frame: Baseline, Month 3, Month 6, Month 9, Year 1
Change in Claudication Onset Time (COT)
Time frame: Baseline, Month 3, Month 6, Month 9
Change in Ankle-Brachial Index (ABI)
Time frame: Baseline, Month 3, Month 6, Month 9
Change in Foot Transcutaneous Oxygen Tension (TcPO2)
Time frame: Baseline, Month 3, Month 6, Month 9
Number of Circulating Mononuclear Cells Expressing CD34
Time frame: Baseline, Week 3, Month 3, Week 15, Month 6, Month 9
Number of Circulating Mononuclear Cells Expressing CD133
Time frame: Baseline, Week 3, Month 3, Week 15, Month 6, Month 9
Number of Circulating Mononuclear Cells Expressing VEGF2R (KDR)
Time frame: Baseline, Week 3, Month 3, Week 15, Month 6, Month 9
Number of Circulating Mononuclear Cells Expressing CXCR4
Time frame: Baseline, Week 3, Month 3, Week 15, Month 6, Month 9
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2026.
- Derived from this study: PubMed 32145440Mehta A, Mavromatis K, Ko YA, Rogers SC, Dhindsa DS, Goodwin C, Patel R, Martini MA, Prasad M, Mokhtari A, Hesaroieh IG, Frohwein SC, Kutner MH, Harzand A, Wells BJ, Duwayri Y, Alabi O, Rajani RR, Brewster LP, Waller EK, Quyyumi AA. Rationale and design of the granulocyte-macrophage colony stimulating factor in peripheral arterial disease (GPAD-3) study. Contemp Clin Trials. 2020 Apr;91:105975. doi: 10.1016/j.cct.2020.105975. Epub 2020 Mar 4.
- Individual participant dataSharing planned: No
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Personalised Multicomponent Exercise Programme in Peripheral Arterial Disease
Peripheral Arterial Disease, Intermittent Claudication
Active, not recruitingObservational study
Laser Atherectomy and Sirolimus-eluting Balloon Angioplasty for CLTI
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A Bioequivalence and Safety Study of AJU-B718 and B718R in Healthy Adult Volunteers Under Fasting Conditions
Peripheral Arterial Disease
Active, not recruitingPhase 4
Ramipril Treatment of Claudication: Oxidative Damage and Muscle Fibrosis
Peripheral Arterial Disease
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.
Arshed Quyyumi, MD principal investigator
Emory University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GM-CSF in people with Peripheral Artery Disease (PAD), run by Emory University at 1 site in United States.
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 9 inclusion and 23 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 12 Aug 2026. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 6-minute walk distance (time frame: Baseline, Month 6). 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 NCT03304821, which also lists 1 linked publication.
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 12 Aug 2026.