A Clinical and Histological Analysis of Mesenchymal Stem Cells in Amputation

NCT ID: NCT02685098

Last Updated: 2025-09-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 81 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-23
• Study Completion Date: 2023-10-03

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.

Detailed Description

This is a phase I single center open label trial study that will enroll twenty-six (26) patients requiring semi-elective lower extremity major amputation within a 30 day period for non-infectious complications related to critical limb ischemia (CLI). After enrollment patients will be scheduled for amputation 7 days after MSC administration. The investigational treatment uses allogeneic bone marrow derived mesenchymal stem cells at the point of care. Allogeneic MSCs will be injected in the gastrocnemius muscle and anterior tibialis muscle of twenty-six (26) patients undergoing major amputation. Through a review of treatment related adverse events over 6 months we will test the hypothesis that allogeneic MSCs do not result in significant cardiovascular, respiratory, or infectious treatment related adverse events. Through an exploratory investigation we will assess the efficacy of MSCs in promoting freedom from gangrene, revision of amputation, and death after major amputation.

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Active/Treatment Group

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

Group Type: EXPERIMENTAL

Allogeneic bone marrow derived mesenchymal stem cells

Intervention Type: 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.

Observation Group 1

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Observation Group 2

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Observation Group 3

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Control Group 4

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Allogeneic bone marrow derived mesenchymal stem cells

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.

Intervention Type: BIOLOGICAL

Other Intervention Names

cBMA; MSCs

Eligibility Criteria

Inclusion Criteria

1. Be ≥ 40 and ≤90 years of age.

2. Patients requiring lower extremity major amputation, as determined by an independent vascular specialist.

3. 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)

4. Amputation can safely be performed up to 30 days after screening, as determined by an independent vascular or orthopedic surgeon.

5. 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.

Exclusion Criteria

1. Patients who are pregnant, planning to become pregnant in the next 12 months, or lactating.

2. CHF hospitalization within the last 1 month prior to enrollment.*

3. Acute coronary syndrome in the last 1 month prior to enrollment.*

4. HIV positive, or active, untreated HCV as determined by review of medical records.

5. History of cancer within the last 5 years, except basal cell skin carcinoma

6. Inability to provide written informed consent due to cognitive or language barriers (interpreter permitted).

7. Concurrent enrollment in another clinical investigative trial that may alter the outcomes of enrollment in this trial.

8. Any condition requiring immunosuppressant medications (e.g., for treatment of organ transplants, psoriasis, Crohn's disease, alopecia areata).

9. 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.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Indiana University

OTHER

Sponsor Role: lead

Responsible Party

Michael Murphy

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michael P Murphy, MD

Role: PRINCIPAL_INVESTIGATOR

Indiana University

Locations

Indiana University

Indianapolis, Indiana, United States

Countries

United States

References

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)

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.

Reference Type: DERIVED

PMID: 29395424 (View on PubMed)

Other Identifiers

1505714405

Identifier Type: -

Identifier Source: org_study_id