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

Peripheral Arterial Disease Clinical Trial

— MOBILE  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01049919
• Other study ID #: BB-IDE 13996
• Secondary ID: BBIO.CR.CT002
• Status: Terminated
• Phase: N/A
• Start date: June 2010
• Est. completion date: February 2020

Study information

• Verified date: May 2021
• Source: Zimmer Biomet
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 153
• Est. completion date: February 2020
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

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

Procedure:
• Placebo procedure (sham)
Sham bone marrow aspiration, sham delivery to affected limb

Locations

Country	Name	City	State
United States	Piedmont Hospital	Atlanta	Georgia
United States	Tufts Medical Center	Boston	Massachusetts
United States	University of Virginia Hospital	Charlottesville	Virginia
United States	Northwestern University	Chicago	Illinois
United States	The Cleveland Clinic	Cleveland	Ohio
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Remington-Davis	Columbus	Ohio
United States	Spectrum Health	Grand Rapids	Michigan
United States	The Methodist Hospital	Houston	Texas
United States	Indiana University School of Medicine	Indianapolis	Indiana
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Saint Luke's Hospital	Kansas City	Missouri
United States	Central Arkansas Veterans Healthcare System	Little Rock	Arkansas
United States	University of Louisville	Louisville	Kentucky
United States	University of Miami	Miami	Florida
United States	Aurora St. Luke's Medical Center	Milwaukee	Wisconsin
United States	The Mount Sinai Hospital	New York	New York
United States	Weill Cornell Medical College / New York-Presbyterian Hospital	New York	New York
United States	Nebraska-Western Iowa VA Healthcare System	Omaha	Nebraska
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	VA Pittsburgh Healthcare System	Pittsburgh	Pennsylvania
United States	University of California-Davis Medical Center	Sacramento	California
United States	Providence Sacred Heart Medical Center	Spokane	Washington
United States	Holy Name Medical Center	Teaneck	New Jersey
United States	UMass Memorial Health Care	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Zimmer Biomet

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Primary	Occurrence of Major Amputation or Death	Occurrence of major amputation (above the ankle joint) or death.	52 weeks
Secondary	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
Secondary	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