Study of Autologous Bone Marrow Concentrate for the Treatment of Critical Limb Ischemia (CLI)

Inclusion Criteria:

• Diagnosis of Critical Limb Ischemia per protocol (see diagnostic criteria #2) with regard to the study limb.

Existence of a PAOD with clinical presentation corresponding to Rutherford Category 4 or Category 5 as defined in the reporting standards adopted by the Society of Vascular Surgeons (table 1)

• Patient meets at least one of the following diagnostic criteria in the study limb:

  • Ankle artery occlusion pressure absolute <50 mmHg or ABI <0.4
  • Toe artery occlusive pressure < 40mm Hg or TBI (<0.4)
  • TcPO2 <20 mmHg lying down breathing room air.

• There is no reasonable open surgical or endovascular revascularization option as determined by the treating vascular specialist. Factors that may contribute to the determination of inoperability may include:

  • Anatomical considerations

    • No outflow targets
    • No appropriate conduit (i.e. vein for bypass)
    • Long segment occlusions or calcified lesions that predict poor outcome with endovascular approaches.

  • High risk medical conditions

    • Unstable cardiac disease.
    • Renal insufficiency
  • History of prior failed revascularization attempts

  • The patient's unsuitability must be confirmed by 2 qualified physicians.

    • The attending vascular surgeon will provide the primary assessment.
    • The confirmatory opinion must come from a fully licensed physician. (not a resident)
    • If anatomical considerations are invoked, the second physician may be a vascular surgeon, interventional radiologist, cardiologist, or vascular medicine specialist.
    • If medical co-morbidity is deemed the high risk aspect, then the confirmatory opinion may be obtained from an internist, family physician, cardiologist, vascular medicine, nephrologists, or vascular surgeon.
• Age >18 years and ability to understand the planned treatment
• Subject has read and signed the IRB approved Informed Consent form
• Patients for whom the following medication(s) is prescribed must have a one month stable baseline of appropriate/maximally tolerated therapy prior to enrollment: Plavix/asprin therapy, anticoagulation therapy, cholesterol lowering agent, and or blood pressure medication
• Hematocrit ≥ 28.0%, White Blood Cell count ≤ 14,000, Platelet count ≥ 50,000, Creatinine ≤ 2.0 mg / dL, INR ≤ 1.6 unless on Coumadin, or PTT <1.5 x control (to avoid bleeding complications) Patients on Coumadin will be corrected prior to the procedure and must have an INR<1.6 at the time of randomization/surgery.

Exclusion Criteria:

• Life expectancy <6 months due to concomitant illnesses
• History of bone marrow diseases (especially NHL, MDS) that prohibit transplantation
• Terminal renal failure with existing dependence on dialysis
• Known active malignancy or results outside of normal limits from the following tests: PAP, Chest X-ray, PSA, Mammogram, Hemoccult unless follow-up studies reveal patient to be cancer free..
• Poorly controlled diabetes mellitus (HgbA1C>10%)
• Medical risk that precludes anesthesia (conscious sedation), or ASA Class 5
• Life-threatening complications of the ischemia necessitating immediate amputation
• Uncorrected iliac artery occlusion on index side
• No Doppler signal in the foot (ABI =0)
• Extensive necrosis of the index limb or other conditions that make amputation inevitable (Rutherford Category 6)
• Active clinical infection being treated by antibiotics within one week of enrollment
• Treatment with immunosuppressant drugs (including Prednisone > 5 mg per day).
• Female who is pregnant or nursing, or of child bearing potential and is not using a reliable birth control method.
• Underwent a major open cardiovascular surgical procedure (carotid endarterectomy, arterial aneurysm or bypass surgery, or coronary artery bypass surgery) or a myocardial infarction within the 3 months prior to randomization
• Cerebrovascular accident within 6 months prior to randomization.