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 12, 2020
|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|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||16 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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|
Experimental: Active/Treatment Group
Amputation performed at 7 days post allogeneic bone marrow derived mesenchymal stem cell injections.
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 7 days before amputation.
No Intervention: 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.
No Intervention: 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.
No Intervention: 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.
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 visits will occur.
- 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.
- 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.
- 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.
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
|Contact: Kristen Wanczyk, RN, CCRCfirstname.lastname@example.org|
|Contact: Karen Lynn, Admin Asstemail@example.com|
|United States, Indiana|
|Indianapolis, Indiana, United States, 46202|
|Contact: Kristen E Wanczyk, RN, CCRC 317-988-9548 firstname.lastname@example.org|
|Principal Investigator:||Michael P Murphy, MD||Indiana University|