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:

* 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
B: Inclusion Criteria:

* Patients with PAOD (Stage III or IV)
* Distal arterial occlusions
* Patients with Buergers Disease
* Signed informed consent

Exclusion Criteria:

* Successful bypass operation or intervention within the last 3 months
* Active infection, feber, chronic inflammatory disease
* HIV, Hepatitis
* Tumor within the last 5 years, complete remission required
* Stroke or myocardial infarction within last 3 months
* Renal insufficiency (creatinine \> 2 mg/dl)
* Liver disease (GOT \> 2x upper limit oder spontaneous INR \> 1,5).
* Anemia (hemoglobin \< \<10 mg/dl)
* Thrombocytopenia \< 100.000/µl
* Allergies to Aspirin, Clopidogrel, Heparin
* Bleeding disorder
* Gastrointestinal bleeding within last 3 months
* Surgery or trauma within the last 2 months
* Pregnancy
* Mental retardation
* Inclusion in other clinical study within last 30 days
C: 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.
D: Inclusion Criteria:

* Patients with unilateral critical chronic limb ischemia but not suitable candidates for non-surgical or surgical revascularization
* Before being included, the patient must be screened for human immunodeficiency virus, hepatitis B virus, hepatitis C virus, treponema pallidum

Exclusion Criteria:

* Buerger disease
* Ischemic ulcers with infectious symptoms
* Diabetes mellitus with HbA1c \> 7,5% or with proliferative retinopathy
* Past or current malignancy
* Contra-indication to general anaesthesia
* Chronic haemodialysis
* Prothrombin Time \< 60%,
* Recent onset (within 3 months) of myocardial infarction or brain infarction
* Coronary angioplasty within 1 year
* Atrial fibrillation, mechanical mitral prosthetic valve
* Unexplained hematological abnormality.
* Expected life span less than six months
* Patient not competent to give informed consent

Answer: A