Safety and Efficacy Study of Autologous Concentrated Bone Marrow Aspirate (cBMA) for Critical Limb Ischemia (CLI) (MOBILE)

• Long-term treatment failure [ Time Frame: 5 years ]
  Evaluations of long-term amputation-free survival will be assessed for a period of 5 years.
• Long-term perfusion and quality of life measurements [ Time Frame: 3 years ]
  ABI, TBI, rest pain, 6 Minute Walk Test, VascuQol, SF-36, wound assessment, minor amputations, time to major amputation of the index limb, time to death

• Critical Limb Ischemia
• Peripheral Arterial Disease
• Peripheral Vascular Disease

• Device: Bone marrow concentration device
  Concentration of autologous bone marrow aspirate for intramuscular delivery to affected limb
  Other Names:

  • Bone marrow concentrate
  • Bone marrow mononuclear cells
  • MarrowStim
• Procedure: Placebo procedure (sham)
  Sham bone marrow aspiration, sham delivery to affected limb

• Experimental: Concentrated bone marrow aspirate (cBMA)
  Collection of autologous bone marrow aspirate and point-of-care concentration using the bone marrow concentration device, followed by intramuscular injection of concentrated bone marrow aspirate (cBMA) into the affected limb
  Intervention: Device: Bone marrow concentration device
• Sham Comparator: Placebo control (sham)
  Placebo procedure (sham) consists of simulated bone marrow aspiration followed by simulated intramuscular injections into the affected limb
  Intervention: Procedure: Placebo procedure (sham)

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) with ABI ≤ 0.6, or TBI ≤ 0.4, or TcPO2 ≤ 50 mm Hg
• 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 on oral or insulin therapy with uncontrolled or untreated proliferative retinopathy (evidence of retinal exam required)
• Poorly controlled diabetes mellitus with HbA1C > 10% (evidence of HbA1C test required)
• Uncompensated congestive heart failure (New York Heart Association Class IV) 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 normal upper limit)
• 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.