GM-CSF for Peripheral Arterial Disease
(GPAD-3 Trial)
Recruiting in Palo Alto (17 mi)
Overseen byArshed Quyyumi, MD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Emory University
Must be taking: Statins
Must not be taking: Immunosuppressants
Disqualifiers: Active infections, Cancer, Heart failure, others
Prior Safety Data
Trial Summary
What is the purpose of this trial?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.
Do I need to stop my current medications to join the trial?
The trial does not specify if you need to stop taking your current medications. However, you must be on stable medical therapy for atherosclerosis and statin therapy for at least 2-3 months before joining. If you are taking immunosuppressant drugs, you cannot participate.
What data supports the effectiveness of the drug GM-CSF for treating peripheral arterial disease?
Research suggests that GM-CSF may help improve walking distance and exercise capacity in patients with peripheral arterial disease by mobilizing progenitor cells, which are cells that can help repair blood vessels. Some studies have shown promising results in improving symptoms like claudication (pain caused by too little blood flow) in these patients.
12345Is GM-CSF safe for humans?
GM-CSF (Granulocyte-Macrophage Colony-Stimulating Factor) is generally safe for humans when used at appropriate doses, with mild-to-moderate side effects like fever, muscle pain, and rash occurring in 20-30% of patients. High doses can cause severe side effects, so careful monitoring is needed, especially in certain patient groups.
12678How does the drug GM-CSF differ from other treatments for peripheral arterial disease?
GM-CSF is unique because it works by mobilizing progenitor cells from the bone marrow to improve blood vessel function and increase walking distance in patients with peripheral arterial disease, offering a non-invasive alternative to surgery or angioplasty.
12456Eligibility Criteria
This trial is for people with Peripheral Arterial Disease (PAD) who have been on statin therapy, can consent to the study, and have stable PAD symptoms. They must not have severe heart failure, recent major cardiovascular events or surgeries, uncontrolled diabetes, active cancer treatment, or any condition that would limit participation.Inclusion Criteria
My walking impairment has been stable for the last 2 months.
I have been on statin therapy for the last 3 months or I cannot tolerate statins.
I am a woman who is either post-menopausal, surgically sterile, not pregnant, using birth control, and not breastfeeding.
+6 more
Exclusion Criteria
I have had a blood cancer affecting my bone marrow before.
I have had an amputation below or above the knee, or I use a wheelchair.
I use a walking aid that is not a cane.
+19 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
4 weeks
1 visit (in-person)
Initial Treatment
Participants receive injections of GM-CSF or placebo three times a week for three weeks
3 weeks
9 visits (in-person)
Interim Follow-up
Participants are monitored for changes in walking performance and other health metrics
3 months
1 visit (in-person)
Second Treatment
Participants receive a second round of injections of GM-CSF or placebo three times a week for three weeks
3 weeks
9 visits (in-person)
Final Follow-up
Participants are monitored for changes in walking performance and other health metrics
3 months
1 visit (in-person)
Long-term Follow-up
Participants are contacted via telephone to administer questionnaires and collect adverse event data
3 years
3 visits (telephone)
Participant Groups
The trial tests if GM-CSF injections improve blood flow and symptoms in PAD patients compared to a placebo. Participants will receive either GM-CSF or placebo shots three times weekly for two three-week periods with a follow-up at six months to assess improvement.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: GM-CSFExperimental Treatment1 Intervention
Participants receiving 500µg of granulocyte-macrophage colony stimulating factor (GM-CSF), administered subcutaneously. Prior to randomization to a study arm, eligible participants will be 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.
Group II: PlaceboPlacebo Group1 Intervention
Participants receiving 500µg of a placebo, administered subcutaneously. Prior to randomization to a study arm, eligible participants will be 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.
GM-CSF is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Leukine for:
- Neutropenia
- Bone Marrow Transplantation
- Leukemia
- Lymphoma
- HIV Infection
🇪🇺 Approved in European Union as Sargramostim for:
- Neutropenia
- Bone Marrow Transplantation
- Leukemia
- Lymphoma
🇨🇦 Approved in Canada as Leukine for:
- Neutropenia
- Bone Marrow Transplantation
- Leukemia
- Lymphoma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Emory University HospitalAtlanta, GA
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Who Is Running the Clinical Trial?
Emory UniversityLead Sponsor
National Heart, Lung, and Blood Institute (NHLBI)Collaborator
References
Bone marrow mobilization with granulocyte macrophage colony-stimulating factor improves endothelial dysfunction and exercise capacity in patients with peripheral arterial disease. [2015]We hypothesized that granulocyte macrophage colony-stimulating factor (GM-CSF) administration will be safe and will improve endothelial dysfunction and exercise capacity by mobilizing progenitor cells in patients with peripheral arterial disease (PAD).
Design of the START-trial: STimulation of ARTeriogenesis using subcutaneous application of GM-CSF as a new treatment for peripheral vascular disease. A randomized, double-blind, placebo-controlled trial. [2017]Peripheral arterial disease (PAD) affects a large percentage of the elderly population. Standard invasive treatment, apart from risk factor modulation, consists of bypass surgery or percutaneous transluminal angioplasty. However, symptomatic recurrence rates are high for both procedures and a substantial part of the patient population with PAD is not a candidate for invasive revascularization due to complexity of the lesion and/or co-morbidity. Therapeutic arteriogenesis has been proposed as an alternative treatment option. The present paper describes the design of the START-trial. This trial aims to determine the potential of the pro-arteriogenic substance granulocyte/macrophage colony stimulating factor (GM-CSF) to increase maximal walking distance in patients with intermittent claudication. A double-blinded, randomized, placebo-controlled study will be performed in 40 patients with peripheral obstructive arterial disease Rutherford grade I, category 2 or 3, that are candidates for bypass surgery or percutaneous transluminal angioplasty. Based on pharmacokinetic and toxicologic studies, a dose of 10 microg/kg will be used. Patients will be treated for a period of 14 days on each consecutive day, with the last injection applied on day 12. The primary endpoint will be the change in walking distance from day 0 to day 14 as assessed by an exercise treadmill test. Secondary endpoints will be the ankle-brachial index at rest and after exercise, the pain-free walking distance and cutaneous microcirculatory alterations as assessed by laser Doppler fluxmetry. Iliac flow reserve and conductance will be measured by magnetic resonance imaging.
Rationale and design of the granulocyte-macrophage colony stimulating factor in peripheral arterial disease (GPAD-3) study. [2021]Lower extremity peripheral arterial disease (PAD) is a public health problem and many patients with PAD experience claudication despite adequate medical and/or surgical management. Mobilization of endogenous progenitor cells using Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) is a novel therapeutic option that has shown promising results in experimental models and phase I/IIA clinical trials. The GPAD-3 trial will study the effect of two successive administrations of GM-CSF at 3-month interval for improving claudication among patients with lower extremity PAD.
Granulocyte colony-stimulating factor: a noninvasive regeneration therapy for treating atherosclerotic peripheral artery disease. [2022]The purpose of this study was to determine whether treatment with granulocyte colony-stimulating factor (G-CSF), which mobilizes endothelial progenitor cells from bone marrow, can safely improve the clinical outcomes of patients with atherosclerotic peripheral artery disease (PAD).
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. [2018]Benefits of granulocyte-macrophage colony-stimulating factor (GM-CSF) for improving walking ability in people with lower extremity peripheral artery disease (PAD) are unclear. Walking exercise may augment the effects of GM-CSF in PAD, since exercise-induced ischemia enhances progenitor cell release and may promote progenitor cell homing to ischemic calf muscle.
START Trial: a pilot study on STimulation of ARTeriogenesis using subcutaneous application of granulocyte-macrophage colony-stimulating factor as a new treatment for peripheral vascular disease. [2011]Granulocyte-macrophage colony-stimulating factor (GM-CSF) was recently shown to increase collateral flow index in patients with coronary artery disease. Experimental models showed beneficial effects of GM-CSF on collateral artery growth in the peripheral circulation. Thus, in the present study, we evaluated the effects of GM-CSF in patients with peripheral artery disease.
The side-effect profile of GM-CSF. [2019]Granulocyte-macrophage colony-stimulating factor (GM-CSF), a pleiotropic molecule which displays a broad range of haematopoietic activities, has become available for clinical evaluation in various patient groups. It has been shown to be effective in preventing or reversing neutropenia. Adverse effects of GM-CSF, however, are dose related. Appropriate dose, route and schedules for GM-CSF in various clinical settings have recently been defined, the usual range being 5-10 micrograms/kg/day either by 4-6 h intravenous infusion or by subcutaneous injection. At such doses, adverse effects are predominantly mild-to-moderate in nature, occur in 20-30% of patients and usually comprise fever, myalgia, malaise, rash and injection site reaction. Early trials using very high doses of GM-CSF were often associated with marked adverse effects, which in rare cases proved severe (pericarditis and thrombosis). Similarly, a so-called "first-dose reaction", defined as a syndrome of hypoxia and hypotension after the initial but not subsequent doses of GM-CSF, was observed in certain predisposed patients following doses above 10 micrograms/kg/day. Subsequent trials have established that intravenous bolus or short infusions of GM-CSF are more likely to promote adverse effects. Certain patient groups, for example those with myelodysplastic syndrome, acute myeloid leukaemia, inflammatory disease, autoimmune thrombocytopenia or malfunctional immunological responsiveness, require careful clinical monitoring in order to avoid potential complications following the administration of GM-CSF. With the current appropriate administration and doses of GM-CSF, the benefit:risk ratio has been greatly improved.
Comparison of hospitalization risk and associated costs among patients receiving sargramostim, filgrastim, and pegfilgrastim for chemotherapy-induced neutropenia. [2022]Sargramostim is a granulocyte-macrophage-colony-stimulating factor (GM-CSF). Unlike filgrastim and pegfilgrastim, which are granulocyte-colony-stimulating factors (G-CSFs), sargramostim activates a broader range of myeloid lineage-derived cells. Therefore, GM-CSF might reduce infection risk more than the G-CSFs. This study compared real-world infection-related hospitalization rates and costs in patients using G/GM-CSF for chemotherapy-induced neutropenia.