Clinical trial NCT02685098: A Clinical and Histological Analysis of Mesenchymal Stem Cells in Amputation
Official title: A Clinical and Histological Analysis of Mesenchymal Stem Cells in Amputation
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
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
Lead sponsor: Indiana University
Sponsor class: OTHER
First posted: 2016-02-18
Enrollment: 81
Sex: ALL
Minimum age (years): 40
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: Number of participants with treatment-related adverse events occurring during the enrollment period as assessed by the Investigator using the MeDRA scale.
timeFrame: Primary follow up in a 6 month period
Secondary outcomes:
measure: 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.
timeFrame: Primary follow up in a 6 month period
measure: 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.
timeFrame: Primary follow up in a 6 month period
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
Study officials:
affiliation: Indiana University
name: Michael P Murphy, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.