Granulocyte-Macrophage Stimulating Factor in the Treatment of Peripheral Arterial Disease
Condition: Peripheral Arterial Disease
MeSH terms: Peripheral Arterial Disease; Peripheral Vascular Diseases
Intervention: Granulocyte-Macrophage Stimulating Factor (GM-CSF); Placebo
Intervention description: 500 micrograms of GM-CSF; Saline injection
Intervention MeSH terms: Molgramostim; Sargramostim
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 159.0
Sex: All
Minimum age: 21 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: claudication

Summary:

      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.
    

Eligibility 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.