Please select the eligibility criteria that correspond to the clinical trial below.
Title: Intra-arterial Infusion of Autologous Bone Marrow Mononuclear Cells in Patients With Chronic Critical Limb Ischemia: a Randomized, Placebo-controlled Clinical Trial
Brief Summary: The purposes of this study are to determine whether intra-arterial injection of autologous stem cells is effective in the treatment of chronic limb ischemia (CLI), to characterize stem cell dysfunction in patients with CLI, and to relate the stem cell function with clinical outcome.


Options:
A: Inclusion Criteria:

* Unilateral or bilateral lower extremity ischemia due to advanced peripheral arterial disease
* Unsuitable for revascularization
* Minor tissue loss (Rutherford Category 5) or ischemic rest pain (Rutherford Category 4)
* Competent to give consent
* No current malignancy or history of previous malignancy within the last five years, with the exception of adequately treated non-melanoma skin cancer (evidence of standard preventative cancer screenings required)

Exclusion Criteria:

* Major tissue loss (Rutherford Category 6)
* Diabetics with uncontrolled or untreated proliferative retinopathy
* Poorly controlled diabetes mellitus with HbA1C \> 10%
* Uncompensated congestive heart failure and/or other conditions that preclude general anesthesia
* Myocardial infarction or stroke within last 90 days
* Elevated liver function tests (AST or ALT more than twice the upper limit of normal)
* Renal disease (creatinine \> 2.5 mg/dl) or chronic hemodialysis
* White blood cell count \< 3,000/µL or \> 15,000/µL, platelet count \< 100,000/µL, or hematocrit \< 32%
* Topical growth hormone therapy within last 90 days, or injected growth hormone therapy within last 180 days
* Disease of central nervous system and/or other conditions that impair cognitive function
* Two or more episodes of pulmonary embolus with a documented DVT in index leg or history of DVT in index leg without evidence of clot resolution
* Current infection of index leg
* Pregnant women (negative urine pregnancy test required)
* Lower extremity venous disease with pitting edema in index leg
* Recent history (in the 6 months prior to screening) of bone marrow disease or treatment with any medication or procedure which adversely affects the bone marrow and would prohibit transplantation
* Current osteomyelitis in index leg
* Existing HIV diagnosis
* Organ transplant recipients
* Known terminal disease process with life expectancy less than one year
* Severe concomitant disease(s) or any additional condition(s) which the investigator feels constitute(s) criteria for exclusion of a particular subject
* Major amputation required within 30 days
* Inclusion in any other clinical study that may affect the outcome of this study
* Uncorrected stenosis(es) of greater than 50% in the common and/or external iliac artery and/or common femoral artery of the index leg.
B: 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;
C: Inclusion Criteria:

* Diabetic patients under treatment (type I or II)
* Critical limb ischemia (rest pain and/or non-healing ischemic ulcers lasting more than 4 weeks, and/or Ankle-Brachial Index \< 0,8)
* Not suitable to be revascularized (surgical and interventional consensus)

Exclusion Criteria:

* Neoplastic disease and/or hematologic disease during the last 2 years
* Diabetic retinopathy
* Ischemic ulcer greater than 10 cm2
* Major amputation at target limb
* Life expectancy \> 2 years
D: Inclusion Criteria:

* Age \> 18 years
* Severe infra-popliteal peripheral arterial occlusive disease \[PAOD\] (Fontaine class IIb, III or IV)
* Invalidating intermittent claudication, persistent, recurring rest pain requiring analgesia and/or non-healing ulcers present for \> 4 weeks without evidence of improvement in response to conventional therapies
* Ankle brachial index \< 0.6 or "unreliable"
* Not eligible for surgical or radiological 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
* Anticipated inability to obtain 100 ml of bone marrow aspirate
* Known infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C virus
* Follow-up impossible

Answer: D