Granulocyte-Macrophage Stimulating Factor (GM-CSF) in Peripheral Arterial Disease (GPAD-3)
Peripheral Artery Disease (PAD)
About this trial
This is an interventional treatment trial for Peripheral Artery Disease (PAD) focused on measuring Atherosclerotic peripheral artery disease, Granulocyte-macrophage colony stimulating factor (GM-CSF), Atherosclerosis, Cardiology, Vascular disease
Eligibility Criteria
Inclusion Criteria:
- 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.
- 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.
Exclusion Criteria:
- 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
- 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
Sites / Locations
- Emory University HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
GM-CSF
Placebo
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.
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.