A Clinical and Histological Analysis of Mesenchymal Stem Cells in Amputation

NCT02685098 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 1505714405
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 1

Brief Summary

Patients undergoing semi-elective lower extremity major amputation from complications associated with atherosclerotic limb ischemia will received intra-muscular injections of allogeneic Mesenchymal Stromal Cells in the leg above and below the point of amputation to prevent ischemic wound complications after surgery and decrease the incidence of revision and further amputation. Cohort Groups 1-4 will serve as controls.

Conditions

Ischemia; Peripheral Arterial Disease; Peripheral Vascular Disease; Vascular Disease; Arterial Occlusive Disease; Arteriosclerosis; Atherosclerosis; Cardiovascular Disease; Pathologic Processes; Orthopedic Procedures; Amputation

Keywords

Stem cells; MSCs; Mesenchymal; Amputation; BKA; below knee amputation; CHAMP; AKA; Above Knee Amputation; Stromal cells; bone marrow stem cell injection; Allogeneic

Outcome Measures

Primary Outcomes (1)

• Number of participants with treatment-related adverse events occurring during the enrollment period as assessed by the Investigator using the MeDRA scale.

  Treatment-related adverse events will be categorized in overlapping systems of cardiovascular, respiratory, or infectious and severities of serious adverse events (SAE) and major adverse cardiac events (MACE). The sum and difference between routes of delivery will be reported. Confidence intervals will be generated and summarize the data by the method of the Wilson Score Interval. Binomial confidence intervals at the 95% confidence level and p-values for these groups will be calculated. Continuous confidence intervals at the 95% level will be constructed to explore the effect of administration of MSCs on the composite endpoint at 6-months of death, amputation revision and gangrene, and will be compared to historical cohorts. The critical levels for the multiplicity adjustment will be determined by simple Monte Carlo simulation.Unanticipated SAEs and those affecting the rights, safety, or welfare of subjects will be documented and reported immediately upon discovery.

  Primary follow up in a 6 month period

Secondary Outcomes (2)

• Gene and protein arrays, IHC staining, and multiparametric flow cytometry will measure the time period of retention of allogeneic MSCs in harvested human skeletal muscle tissue post-MSC implantation.

  Primary follow up in a 6 month period

• Recruitment of proangiogenic hematopoietic cells into sites of ischemia will be measured and reported as assessed by the role of MSCs injected in human skeletal muscle at the time of amputation.

  Primary follow up in a 6 month period

Study Arms (5)

Active/Treatment Group

EXPERIMENTAL

Amputation performed at 7 days post allogeneic bone marrow derived mesenchymal stem cell injections.

Biological: Allogeneic bone marrow derived mesenchymal stem cells

Observation Group 1

NO INTERVENTION

Amputation performed with no MSC administration. Subjects will be followed for incidence of infection and wound healing status to week 24 as a comparator to the Active/Treatment group.

Observation Group 2

NO INTERVENTION

Tissue Collection Group: Amputation performed with no MSC administration. Subjects will not be followed after amputation is performed. Tissue collection will occur at time of amputation.

Observation Group 3

NO INTERVENTION

Patients undergoing lower extremity bypass grafting procedure. Skeletal muscle samples of the sartorius and anterior tibial muscle will be collected for comparison to treatment group. No study testing, nor follow up visits will occur.

Control Group 4

NO INTERVENTION

Patients undergoing a standard of care surgical procedure under anesthesia. Core needle biopsies will be collected from the anterior tibial muscle at the time of surgical procedure. No study testing, nor follow up visits will occur.

Interventions

Allogeneic bone marrow derived mesenchymal stem cells BIOLOGICAL

Injection of HLA-A2+ and/or gender mismatched allogeneic MSCs above the site of amputation and into the anterior tibialis muscle (ATM) of patients scheduled for semi-elective lower extremity major amputation at 7 days before amputation.

Also known as: cBMA, MSCs

Active/Treatment Group

Eligibility Criteria

• Age: 40 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be ≥ 40 and ≤90 years of age.
• Patients requiring lower extremity major amputation, as determined by an independent vascular specialist.
• If ulceration or gangrene present, it is distal to malleoli (to allow adequate length of ATM area of approximately 3cm x 10cm x 3 cm)
• Amputation can safely be performed up to 30 days after screening, as determined by an independent vascular or orthopedic surgeon.
• Females of childbearing potential must be willing to use one form of birth control for the duration of the study. Female participants must undergo a blood or urine pregnancy test at screening.

You may not qualify if:

• Patients who are pregnant, planning to become pregnant in the next 12 months, or lactating.
• CHF hospitalization within the last 1 month prior to enrollment.\*
• Acute coronary syndrome in the last 1 month prior to enrollment.\*
• HIV positive, or active, untreated HCV as determined by review of medical records.
• History of cancer within the last 5 years, except basal cell skin carcinoma
• Inability to provide written informed consent due to cognitive or language barriers (interpreter permitted).
• Concurrent enrollment in another clinical investigative trial that may alter the outcomes of enrollment in this trial.
• Any condition requiring immunosuppressant medications (e.g., for treatment of organ transplants, psoriasis, Crohn's disease, alopecia areata).
• Presence of any clinical condition that in the opinion of the PI or the sponsor makes the patient not suitable to participate in the trial.
• As defined by the standard definitions of CHF and ACS by the American Heart Association.

Sponsors & Collaborators

• Indiana University: lead

Study Sites (1)

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Related Publications (2)

• 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.

  PMID: 21514773 BACKGROUND

• Wang SK, Green LA, Drucker NA, Motaganahalli RL, Fajardo A, Murphy MP. Rationale and design of the Clinical and Histologic Analysis of Mesenchymal Stromal Cells in AmPutations (CHAMP) trial investigating the therapeutic mechanism of mesenchymal stromal cells in the treatment of critical limb ischemia. J Vasc Surg. 2018 Jul;68(1):176-181.e1. doi: 10.1016/j.jvs.2017.09.057. Epub 2018 Feb 1.

  PMID: 29395424 DERIVED

MeSH Terms

Conditions

Ischemia; Peripheral Arterial Disease; Peripheral Vascular Diseases; Vascular Diseases; Arterial Occlusive Diseases; Arteriosclerosis; Atherosclerosis; Cardiovascular Diseases; Pathologic Processes

Condition Hierarchy (Ancestors)

Pathological Conditions, Signs and Symptoms

Study Officials

• Michael P Murphy, MD

  Indiana University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: February 2, 2016
• First Posted: February 18, 2016
• Study Start: January 23, 2017
• Primary Completion: October 3, 2023
• Study Completion: October 3, 2023
• Last Updated: September 23, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)