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Trial record 17 of 34 for:    stem cell peripheral arterial disease AND marrow

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

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ClinicalTrials.gov Identifier: NCT02685098
Recruitment Status : Recruiting
First Posted : February 18, 2016
Last Update Posted : February 11, 2019
Sponsor:
Information provided by (Responsible Party):
Michael Murphy, Indiana University

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.

Condition or disease Intervention/treatment Phase
Ischemia Peripheral Arterial Disease Peripheral Vascular Disease Vascular Disease Arterial Occlusive Disease Arteriosclerosis Atherosclerosis Cardiovascular Disease Pathologic Processes Orthopedic Procedures Amputation Biological: Allogeneic bone marrow derived mesenchymal stem cells Phase 1

Detailed Description:
This is a phase I single center open label trial study that will enroll sixteen 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 randomized to amputation at 3,7,14, or 21 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 thigh muscles and the gastrocnemius muscle (for below knee amputation only) of sixteen 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: A Clinical and Histological Analysis of Mesenchymal Stem Cells in Amputation
Actual Study Start Date : January 2017
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : September 2025

Arm Intervention/treatment
Experimental: Day 3
Amputation performed at 3 days post allogeneic bone marrow derived mesenchymal stem cells injection.
Biological: 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 a randomized time of 3, 7, 14, or 21 days before surgery.
Other Names:
  • cBMA
  • MSCs

Experimental: Day 7
Amputation performed at 7 days post allogeneic bone marrow derived mesenchymal stem cells injection.
Biological: 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 a randomized time of 3, 7, 14, or 21 days before surgery.
Other Names:
  • cBMA
  • MSCs

Experimental: Day 14
Amputation performed at 14 days post allogeneic bone marrow derived mesenchymal stem cells injection.
Biological: 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 a randomized time of 3, 7, 14, or 21 days before surgery.
Other Names:
  • cBMA
  • MSCs

Experimental: Day 21
Amputation performed at 21 days post allogeneic bone marrow derived mesenchymal stem cells injection.
Biological: 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 a randomized time of 3, 7, 14, or 21 days before surgery.
Other Names:
  • cBMA
  • MSCs

No Intervention: Observation Group 1
Amputation performed per standard of care. Study testing and follow up are the same as the intervention groups.
No Intervention: Observation Group 2
Amputation performed per standard of care. Anterior tibial muscle tissue collection to occur at time of amputation. No study testing, nor follow up.
No Intervention: Observation Group 3
Patients undergoing lower extremity bypass grafting. Skeletal muscle samples of the sartorius and anterior tibial muscle will be collected for comparison to treatment group. No study testing, nor follow up.
No Intervention: 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.



Primary Outcome Measures :
  1. Number of participants with treatment-related adverse events occurring during the enrollment period as assessed by the Investigator using the MeDRA scale. [ Time Frame: Primary follow up in a 6 month period ]
    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.


Secondary Outcome Measures :
  1. 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. [ Time Frame: Primary follow up in a 6 month period ]
    Quantities over time of MSC will be fit to an exponential decay curve using a residual pseudo-likelihood procedure and cell half-life (λ) will be estimated. Binomial confidence intervals at the 95% confidence level and p-values will be calculated for the presence or absence of MHC expression and SDF-1activation. The correlation between capillary density (CD31 counts) with tissue perfusion (ICA) for each time point will be estimated by Spearman's rank coefficient. The gene and protein expression profiles and histological findings will be used to test the hypotheses that MSCs have limited survival post-injection.

  2. 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. [ Time Frame: Primary follow up in a 6 month period ]
    Continuous confidence intervals at the 95% level will be constructed to explore differences among the time-tiered administration of MSC for (1) the CD34+CD133+ pro-angiogenic hematopoietic cells recruitment of HIF-1α/SDF-1/CXCR4 to ischemic muscle, (2) the quantify of capillary density in muscle fibers using hematoxylin phloxin saffron and CD31 counts, (3) VEGF-A,C,D, hepatocyte growth factor, angiopoietin-1 to characterize angiogenic cytokine expression, (4) percent coverage, fiber diameter and cross-sectional area to examine changes in morphology. The gene and protein expression profiles and histological findings will be used to test the hypotheses that MSCs act to recruit CD34+CD133+ proangiogenic hematopoietic cells.



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Ages Eligible for Study:   40 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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^2 x 2 cm^2)
  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. Significant hepatic dysfunction (ALT or AST greater than 2 times normal).
  3. CHF hospitalization within the last 1 month prior to enrollment.*
  4. Acute coronary syndrome in the last 1 month prior to enrollment.*
  5. HIV positive, or active, untreated HCV.
  6. History of cancer within the last 5 years, except basal cell skin carcinoma
  7. Any bleeding diathesis defined as an INR ≥ 2.0 (off anticoagulation therapy) or history of platelet count less than 70,000 or hemophilia.
  8. Inability to provide written informed consent due to cognitive or language barriers (interpreter permitted).
  9. Concurrent enrollment in another clinical investigative trial.
  10. Any condition requiring immunosuppressant medications (e.g., for treatment of organ transplants, psoriasis, Crohn's disease, alopecia areata).
  11. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02685098


Contacts
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Contact: Kristen Wanczyk, RN, CCRC 317-988-9548 keevans@iu.edu
Contact: Karen Lynn, Admin Asst 317-988-4043 kgreene@iu.edu

Locations
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United States, Indiana
Indiana University Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Kristen E Wanczyk, RN, CCRC    317-988-9548    keevans@iu.edu   
Sponsors and Collaborators
Indiana University
Investigators
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Principal Investigator: Michael P Murphy, MD Indiana University

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Michael Murphy, MD, Indiana University
ClinicalTrials.gov Identifier: NCT02685098     History of Changes
Other Study ID Numbers: 1505714405
First Posted: February 18, 2016    Key Record Dates
Last Update Posted: February 11, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Michael Murphy, Indiana University:
Stem cells
Stromal cells
bone marrow stem cell injection
MSCs
Mesenchymal
Amputation
BKA
below knee amputation
CHAMP
AKA
Above Knee Amputation
Allogeneic
Additional relevant MeSH terms:
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Atherosclerosis
Vascular Diseases
Peripheral Arterial Disease
Peripheral Vascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Ischemia
Pathologic Processes
Cardiovascular Diseases