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

NCT ID: NCT01049919

Last Updated: 2021-05-28

Study Results

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

NA

Total Enrollment

153 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-06-30

Study Completion Date

2020-02-29

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).

Conditions

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Critical Limb Ischemia Peripheral Arterial Disease Peripheral Vascular Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Outcome Assessors

Study Groups

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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

Group Type EXPERIMENTAL

Bone marrow concentration device

Intervention Type DEVICE

Concentration of autologous bone marrow aspirate for intramuscular delivery to affected limb

Placebo control (sham)

Placebo procedure (sham) consists of simulated bone marrow aspiration followed by simulated intramuscular injections into the affected limb

Group Type SHAM_COMPARATOR

Placebo procedure (sham)

Intervention Type PROCEDURE

Sham bone marrow aspiration, sham delivery to affected limb

Interventions

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Bone marrow concentration device

Concentration of autologous bone marrow aspirate for intramuscular delivery to affected limb

Intervention Type DEVICE

Placebo procedure (sham)

Sham bone marrow aspiration, sham delivery to affected limb

Intervention Type PROCEDURE

Other Intervention Names

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Bone marrow concentrate Bone marrow mononuclear cells MarrowStim

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.
Minimum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Zimmer Biomet

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Michael P. Murphy, MD

Role: PRINCIPAL_INVESTIGATOR

Indiana University School of Medicine

Locations

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Central Arkansas Veterans Healthcare System

Little Rock, Arkansas, United States

Site Status

University of California-Davis Medical Center

Sacramento, California, United States

Site Status

University of Miami

Miami, Florida, United States

Site Status

Piedmont Hospital

Atlanta, Georgia, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

Indiana University School of Medicine

Indianapolis, Indiana, United States

Site Status

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Site Status

University of Louisville

Louisville, Kentucky, United States

Site Status

Tufts Medical Center

Boston, Massachusetts, United States

Site Status

UMass Memorial Health Care

Worcester, Massachusetts, United States

Site Status

Spectrum Health

Grand Rapids, Michigan, United States

Site Status

Saint Luke's Hospital

Kansas City, Missouri, United States

Site Status

Nebraska-Western Iowa VA Healthcare System

Omaha, Nebraska, United States

Site Status

Holy Name Medical Center

Teaneck, New Jersey, United States

Site Status

The Mount Sinai Hospital

New York, New York, United States

Site Status

Weill Cornell Medical College / New York-Presbyterian Hospital

New York, New York, United States

Site Status

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Site Status

The Cleveland Clinic

Cleveland, Ohio, United States

Site Status

Remington-Davis

Columbus, Ohio, United States

Site Status

Temple University Hospital

Philadelphia, Pennsylvania, United States

Site Status

VA Pittsburgh Healthcare System

Pittsburgh, Pennsylvania, United States

Site Status

The Methodist Hospital

Houston, Texas, United States

Site Status

University of Virginia Hospital

Charlottesville, Virginia, United States

Site Status

Providence Sacred Heart Medical Center

Spokane, Washington, United States

Site Status

Aurora St. Luke's Medical Center

Milwaukee, Wisconsin, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 21514773 (View on PubMed)

Other Identifiers

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BBIO.CR.CT002

Identifier Type: OTHER

Identifier Source: secondary_id

BB-IDE 13996

Identifier Type: -

Identifier Source: org_study_id

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