Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Double Blind, Multicentric, Placebo Controlled, Single Dose, Phase - i/ii Study Assessing the Safety and Efficacy of Intramuscular ex Vivo Cultured Adult Allogenic Mesenchymal Stem Cells in Patients With Critical Limb Ischemia (Cli)
Brief Summary: This clinical trial aims to study the safety and efficacy of adult mesenchymal stem cells in critical limb ischemia.


Options:
A: Inclusion Criteria:

* History of exercise-limiting intermittent claudication and peripheral arterial disease with symptoms in one or both legs, of at least 2 months duration with no change in symptom severity in the 2 months prior to screening.
* A Doppler-measured ankle-brachial index (ABI) of ≤0.80 or toe-brachial index (TBI) of \<0.70 in at least one leg after 10 minutes of rest.
* Limitation in walking secondary to claudication with a mean peak walking time (PWT) of between 1 and 10 minutes on a standardized Gardner protocol for exercise treadmill test (ETT).
* Angiographic or equivalent anatomic evidence (MRA) of arterial occlusive disease (\>70%) in the distal common femoral artery or superficial femoral artery and its branches of at least one leg within 12 months prior to screening.
* Postmenopausal (females),surgically sterile, or use adequate birth control.

Exclusion Criteria:

* Presence of significant inflow disease \[defined as \>50% stenosis\] in the distal aorta, common or external iliac as assessed by conventional angiogram, digital subtraction angiography (DSA), or magnetic resonance angiography (MRA) performed \< 1 year prior to screening.
* Critical limb ischemia, either chronic or acute ischemia manifested by rest pain, ulceration, or gangrene (Category 4 through 6 of Society for Vascular Surgery \[SVS\] classification \[Rutherford\]).
* History of malignant neoplasm (except curable non-melanoma skin malignancies).
* Renal failure (serum creatinine \>2.0 mg/dL) or end-stage renal disease(requiring hemodialysis or renal replacement therapy).
* Significant hepatic disease (\>3-fold elevation in ALT/AST).
* HBV or HCV carriers.
* Severe pulmonary disease (e.g. severe chronic obstructive pulmonary disease).
* Subjects with Acute Stroke within 6 months prior to screening.
* Subjects with uncontrolled diabetes mellitus.
* Specific ophthalmologic conditions that preclude retinal photography,vascular lesions of the anterior segment of the eye, proliferative retinopathy, age-related macular degeneration or intra-ocular surgery within 6 months prior to enrollment.
* Gross obesity (BMI≥40).
* Buerger's disease or other forms of inflammatory arteritis.
* Class IV congestive heart failure, as defined by the New York Heart Association or a myocardial infarction within 6 months prior to screening.
* Subject with deep vein thrombosis within 3 months prior to screening.
* Inability to complete the standardized treadmill protocol for reasons other than claudication including symptoms such as angina, dyspnea, joint pains, or excessive fatigue.
* Percutaneous intervention or surgical revascularization in the index lower limb within 6 months prior to enrollment.
* Heart angioplasty with or without stent or coronary bypass surgery within the past 6 months.
* Participation in a structured exercise treatment protocol within 30 days prior to screen testing.
* Subject is planning to participate in a structured exercise treatment protocol during the 180 days following administration of the investigational product.
* Participation in a previous gene transfer trial in which the subject received active investigational product (placebo subjects are eligible).
* Concurrent or prior participation in another clinical trial within 30 days prior to screen testing.
* Chronic use of Cox-2 inhibitors, defined as subjects needing daily use of the agent for more than 30 days prior to screening.
* Subject is taking any of the following drugs for life-threatening conditions or as part of a life-sustaining treatment: Cyclosporine (Sandimmune®),Systemic androgens/anabolic steroids, systemic corticosteroids.
* History of bleeding diathesis (e.g. hemophilia due to Factor VIII or IX deficiency).
* Pregnancy or breast-feeding.
* Uncontrolled hypertension or significant hypotension.
* Immunodeficiency states (e.g, current HIV positivity, or organ transplant recipient) or subject receiving immunosuppressive medications.
* Alcohol or other substance abuse.
B: Inclusion Criteria:

* Clinical diagnosis of third or fourth class of peripheral atherosclerosis

Exclusion Criteria:

* Insuline dependent diabetes
* Cancer
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:

* Males or females with non-child bearing potential in the age group of 18-60 yrs of Indian origin.
* Established CLI, clinically and hemodynamically confirmed as per Rutherford- II-4, III-5, or III-6; Patients having Infra-inguinal arterial occlusive disease with rest pain or ischemic ulcer/necrosis, who are not eligible for or have failed traditional revascularization treatment (No option patients)
* Ankle Brachial Pressure Index (ABPI) ≤ 0.6 or ankle pressure ≤ 70 mm Hg or TcPO2 ≤ 60 mmHg in the foot
* Patients if having associated Type II Diabetes, should be on medication and well controlled (HbA1c ≤ 8%) without complications
* Patients who are able to understand the requirements of the study, and willing to provide voluntary written informed consent, abide by the study requirements, and agree to return for required follow-up visits
* Normal liver and renal function
* On regular medication for hypertension if any

Exclusion Criteria:

* Patients with CLI suitable for surgical or percutaneous revascularization as determined by the surgeon performing vascular procedure and patients with any acute/chronic inflammatory condition
* CLI patient requiring amputation proximal to trans-metatarsal level
* Patients with gait disturbance for reasons other than CLI.
* Type I diabetes
* Patients having respiratory complications/left ventricular ejection fraction \< 25%f) Stroke or myocardial infarction within last 3 months
* Patients who are contraindicated for MRA
* Have clinically serious and/or unstable inter-current infection, medical illnesses or conditions that are uncontrolled or whose control, in the opinion of the Investigator, may be jeopardized by participation in this study or by the complications of this therapy
* Documented terminal illness or cancer or any concomitant disease process with a life expectancy of less than 1 year
* Patients already enrolled in another investigational drug trial or completed within 3 months.
* History of severe alcohol or drug abuse within 3 months of screening.
* Hb% \< 10 gm%, Serum Creatinine ≥ 2mg%, Serum Total Bilirubin ≥2mg%, HbA1c \> 8%
* Women with child bearing potential, pregnant and lactating women.
* Patients tested positive for HIV 1, HCV, HBV,

Answer: D