Please select the eligibility criteria that correspond to the clinical trial below.
Title: Granulocyte-Macrophage Stimulating Factor (GM-CSF) and Mobilization of Progenitor Cells in Peripheral Arterial Disease: A Phase II Randomized Study
Brief 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.


Options:
A: Inclusion Criteria:

* Patients 18 years of age or greater with atherosclerotic vascular disease that is viewed as not readily amenable to reconstructive surgery and Rutherford Category 4 ischemia (ischemic rest pain) and Rutherford Category 5 ischemia (ulceration or tissue necrosis) and by the judgment of their referring physician are not reasonable candidates for revascularization options of either percutaneous balloon angioplasty or a surgical revascularization.
* Objective evidence of severe peripheral arterial disease will include an ankle brachial index (ABI) of less than 0.5, or, in the case of patients who have vessels calcified and thereby "non-compressible" vessels metatarsal pulse volume recording (PVR) that is flat or barely pulsatile in the diseased limb on two consecutive examinations performed at least one week apart.
* Patients competent to give informed consent.
* No active malignant disease that could involve the bone marrow, or history of treatment of malignant disease that could have damaged the bone marrow.
* Before being accepted for the study the patient must be screened for human immunodeficiency virus, hepatitis B virus, hepatitis C virus, human transmissible spongiform encephalopathy, including Creutzfeldt-Jacob Disease, Treponema pallidum, and have a negative standard infectious disease panel including a CMV PCR test.
* Patients who are hemodynamically stable.

Exclusion Criteria:

* Patients with poorly controlled diabetes mellitus (HbA1C \> 8%)
* Patients with renal insufficiency (creatinine \> 2.5).
* Patients with evidence of infectious disease as determined by e. above or other medical findings.
* Pregnant women (women capable of childbearing must have a negative pregnancy test).
* Patients with cognitive impairments.
* Other comorbid disease that would be expected to result in less than one year life expectancy
* Past malignancy or history of chemotherapy or radiation affecting the bone marrow.
* History of inflammatory or progressively fibrotic conditions: .e.g., rheumatoid arthritis, systemic lupus erythematosis, vasculitic disorders, idiopathic pulmonary fibrosis, retroperitoneal fibrosis
* Infection as evidenced by WBC count of \>15,000 and/or temperature \>38 degrees C. Large area of cellulitis in the afflicted limb that in the opinion of the investigators would require the institution of antibiotics OR evidence of osteomyelitis corroborated by radiographic or scintigraphic examination
* Cardiovascular conditions:

  * Exercise limiting angina ( Canadian Cardiovascular Society Class 3 (Appendix 7);
  * Congestive heart failure (New York Heart Association class 3 (Appendix 5);
  * Unstable angina;
  * Acute ST elevation myocardial infarction (MI) within 1month;
  * Transient ischemic attack or stroke within 1 month;
  * Severe valvular disease
* Patients with any history of organ transplants;
B: Inclusion Criteria:

* Age \> 18 years
* Severe Peripheral Artery Disease (PAD; Fontaine class III and / or IV):

  * Fontaine III (Rutherford 4): persistent, recurring rest pain requiring analgesia
  * Fontaine IV (Rutherford 5): non-healing ulcers present for \> 4 weeks without evidence of improvement in response to conventional therapies
* Ankle brachial index \< 0.6 or unreliable (non-compressible or not in proportion to the Fontaine classification)
* Not eligible for surgical or endovascular revascularization
* Written informed consent.

Exclusion Criteria:

* History of neoplasm or malignancy in the past 10 years
* Serious known concomitant disease with life expectancy of less than one year
* Rutherford 6 in which amputation on the short term (within 1-2 weeks) is inevitable
* Pregnancy or unwillingness to use adequate contraception during study
* Uncontrolled acute or chronic infection with systemic symptoms
* Follow-up impossible.
C: Inclusion Criteria:

* Rutherford scale of 4-5
* thromboangiitis obliterans, peripheral arterial disease, or arteritis caused by other etiologies, such as collagen diseases
* surgical or endovascular procedures are considered unlikely to have successful long-term revascularization, or have failed
* more than 4 weeks of critical limb ischemia
* if present, a non-healing ulcer after more than 4 weeks of optimal care by a wound care physician and a nurse

Exclusion Criteria:

* within 3 months of an acute myocardial infarction
* any contraindication for the administration of granulocyte colony stimulating factor (G-CSF)
D: 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.

Answer: D