A Clinical and Histological Analysis of Mesenchymal Stem Cells in Amputation (CHAMP)

Indiana University

Status and phase: Active, not recruiting; Phase 1

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

Treatments: Biological: Allogeneic bone marrow derived mesenchymal stem cells

Study type: Interventional

Funder types: Other

Identifiers

NCT02685098

1505714405

Details and patient eligibility

About

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.

Full 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.

Enrollment: 81 patients

Sex: All

Ages: 40 to 90 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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81 participants in 5 patient groups

Active/Treatment Group

Experimental group

Description:

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

Treatment:

Biological: Allogeneic bone marrow derived mesenchymal stem cells

Observation Group 1

No Intervention group

Description:

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 group

Description:

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 group

Description:

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 group

Description:

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.