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

Study Overview
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Brief Summary
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This trial will evaluate the safety and efficacy of concentrated bone marrow aspirate (cBMA) to prevent or delay major amputation and/or death in subjects with critical limb ischemia (CLI) due to severe peripheral arterial disease (PAD).

Detailed Description
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This is a prospective, randomized, double-blind, placebo controlled, multicenter trial intended for subjects with critical limb ischemia (CLI) that are unsuitable for revascularization. The investigational treatment utilizes autologous concentrated bone marrow aspirate (cBMA) at the point of care. The bone marrow aspirate is obtained from the subject's hip, concentrated with a bone marrow concentration device, and delivered intramuscularly to the affected limb. Subjects meeting the inclusion/exclusion criteria will be randomized to receive either the investigational treatment (cBMA) or a placebo control (sham treatment).

Official Title
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MarrowStim PAD Kit for the Treatment of Critical Limb Ischemia (CLI) in Subjects With Severe Peripheral Arterial Disease (PAD)

Conditions
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Peripheral Vascular Disease, Critical Limb Ischemia, Peripheral Arterial Disease

Intervention / Treatment
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* Device: Bone marrow concentration device
* Procedure: Placebo procedure (sham)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Concentrated bone marrow aspirate (cBMA)<br>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 | Device: Bone marrow concentration device<br>* Concentration of autologous bone marrow aspirate for intramuscular delivery to affected limb<br>* Other names: MarrowStim;|
| Sham Comparator: Placebo control (sham)<br>Placebo procedure (sham) consists of simulated bone marrow aspiration followed by simulated intramuscular injections into the affected limb | Procedure: Placebo procedure (sham)<br>* Sham bone marrow aspiration, sham delivery to affected limb<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of Major Amputation or Death | Occurrence of major amputation (above the ankle joint) or death. | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Analog Scale (VAS) - Pain | Pain reported at the 52-week follow-up visit as assessed on the visual analog scale (VAS). Scores are recorded by making a handwritten mark on a 10-cm line that represents a continuum between no pain and worst pain. The distance from the beginning of the line is measured and reported in centimeters (cm), with 0 representing no pain and 10 representing the worst possible pain. | 52 weeks | 
| Six-Minute Walk Test | Measurement (in meters) of the total distance a participant is able to walk in 6 minutes. Since ability to walk is related to the condition of the affected limb, this measure is tied to limb pain and function. If a participant had multiple limbs included in the study, each limb was evaluated separately. Only one limb could be included in the study at a time. | 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PAD, CLI, Critical Limb Ischemia, Peripheral Arterial Disease, Peripheral Vascular Disease, PVD, Angiogenesis, Stem Cells, Cell Therapy, Limb Salvage, Amputation, Leg Pain