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

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

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).

Study Overview

• Status: Terminated
• Conditions: Peripheral Arterial Disease; Peripheral Vascular Disease; Critical Limb Ischemia
• Intervention / Treatment: Device: Bone marrow concentration device; Procedure: Placebo procedure (sham)

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 153
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Central Arkansas Veterans Healthcare System
  • California
    • Sacramento, California, United States, 95817
      • University Of California-Davis Medical Center
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont Hospital
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University School of Medicine
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
    • Worcester, Massachusetts, United States, 01655
      • UMass Memorial Health Care
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Hospital
  • Nebraska
    • Omaha, Nebraska, United States, 68105
      • Nebraska-Western Iowa VA Healthcare System
  • New Jersey
    • Teaneck, New Jersey, United States, 07666
      • Holy Name Medical Center
  • New York
    • New York, New York, United States, 10029
      • The Mount Sinai Hospital
    • New York, New York, United States, 10065
      • Weill Cornell Medical College / New York-Presbyterian Hospital
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
    • Columbus, Ohio, United States, 43215
      • Remington-Davis
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
    • Pittsburgh, Pennsylvania, United States, 15240
      • VA Pittsburgh Healthcare System
  • Texas
    • Houston, Texas, United States, 77030
      • The Methodist Hospital
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University Of Virginia Hospital
  • Washington
    • Spokane, Washington, United States, 99204
      • Providence Sacred Heart Medical Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora St. Luke's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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	Device: Bone marrow concentration device; Concentration of autologous bone marrow aspirate for intramuscular delivery to affected limb; Other Names: Bone marrow mononuclear cells; Bone marrow concentrate; MarrowStim
Sham Comparator: Placebo control (sham); Placebo procedure (sham) consists of simulated bone marrow aspiration followed by simulated intramuscular injections into the affected limb	Procedure: Placebo procedure (sham); Sham bone marrow aspiration, sham delivery to affected limb

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of Major Amputation or Death	Occurrence of major amputation (above the ankle joint) or death for all participants through final follow-up.	5 years

Collaborators and Investigators

• Sponsor: Zimmer Biomet
• Investigators: Principal Investigator: Michael P. Murphy, MD, Indiana University School of Medicine

Publications and helpful links

General Publications

• Murphy MP, Lawson JH, Rapp BM, Dalsing MC, Klein J, Wilson MG, Hutchins GD, March KL. Autologous bone marrow mononuclear cell therapy is safe and promotes amputation-free survival in patients with critical limb ischemia. J Vasc Surg. 2011 Jun;53(6):1565-74.e1. doi: 10.1016/j.jvs.2011.01.074. Epub 2011 Apr 22.

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): February 1, 2020

Study Registration Dates

• First Submitted: January 14, 2010
• First Submitted That Met QC Criteria: January 14, 2010
• First Posted (Estimate): January 15, 2010

Study Record Updates

• Last Update Posted (Actual): May 28, 2021
• Last Update Submitted That Met QC Criteria: May 5, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Cell Therapy; PAD; Peripheral Vascular Disease; Stem Cells; Angiogenesis; Amputation; PVD; Peripheral Arterial Disease; CLI; Leg Pain; Critical Limb Ischemia; Limb Salvage
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Vascular Diseases; Ischemia; Peripheral Arterial Disease; Peripheral Vascular Diseases
• Other Study ID Numbers: BB-IDE 13996; BBIO.CR.CT002 (Other Identifier: Biomet)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes