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Safety and Efficacy of Allogeneic MSCs in Promoting T-regulatory Cells in Patients With Small Abdominal Aortic Aneurysms

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Disease Information

Descriptive Information
Brief Title † Safety and Efficacy of Allogeneic MSCs in Promoting T-regulatory Cells in Patients With Small Abdominal Aortic Aneurysms
Official Title † Mesenchymal Stem Cells Induce Regulatory T Cells in Patients With Aortic Aneurysm
Brief Summary This project is to determine the safety and explore the effectiveness of allogeneic (not cells of the participant but those of another human) mesenchymal stromal cells (MSCs) in decreasing inflammation and possible enlargement of the participants' abdominal aortic aneurysm. Participants will be selected as a possible subject because of an abdominal aortic aneurysm discovered on the ultrasound or computed tomographic ("CT") scan requested by the participants' doctor. The purpose of this study is to collect information that will be used to determine if MSCs can be used to decrease inflammation and possibly slow down enlargement of the participants' aneurysm. The investigators will also be collecting blood samples to study special inflammatory cells that cause aneurysms as well as asking participants to have a "PET" (positron emission tomography) scan that can measure inflammation directly in the participants' aneurysm.
Detailed Description This is a phase I, double blinded trial that will enroll 36 patients with Abdominal Aortic Aneurysms (AAA) measuring 35-45 mm in maximal transverse diameter (MTD). This study will assess the safety of MSCs in doses of 1 million MSCs/kg. or 3 million MSCs/kg. delivered intra-venously. This trial test the hypothesis that MSCs, in a dose dependent fashion, promote the frequency and immune suppressor function of CD4+CD25+ FoxP3+ T-regulatory cells and decrease AAA inflammation as measured by 18-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT). The primary safety endpoints will be incidence of treatment related adverse events accrued over 24 months. Efficacy measures are changes in frequency and immune suppressor function of Tregs, number and cytotoxic activity of CD4+/CD8+ CD28- T-cells, activated monocytes, and changes in aortic inflammation as measured by uptake of 18-FDG PET/CT compared to baseline. Incidence of surgical intervention, aneurysm related death, quality of life, and major adverse cardiac events will be recorded.
Study Phase Phase 1
Study Type † Interventional
Study Design †
Primary Outcome Measure † Incidence of treatment related adverse events at 12 months post MSC administration as evidenced by the Investigator
Secondary Outcome Measure † Changes in circulating inflammatory cell phenotypes as measured by 18-FDG PET/CT
Condition † Abdominal Aortic Aneurysm
Intervention † BiologicalMSC's or Plasmalyte
Study Arms / Comparison Groups Intravenous infusion of Plasmalyte A (placebo) In a randomized fashion, the Plasmalyte A will be shipped to the performance site where it will be thawed and administered. The Plasmalyte A will be administered within 4 hours to subjects in a monitored setting with telemetry and pulse oximetry as will be performed on active groups in order to protect the blinding of this study. Patients will be pre-medicated with hydrocortisone and diphenhydramine. All subjects will be monitored throughout the infusion procedure with vital signs and pulse oximetry at 15 minutes prior to infusion and ending 2 hours post procedure. They will also be evaluated for clinical signs of pulmonary distress. All patients will be admitted overnight for continued observation. The patient will be examined the following day and discharged home. Intravenous infusion of 1 million allogeneic MSCs/kg In a randomized fashion, the MSCs, in the appropriate dose, will be shipped to the performance site where the MSCs will be thawed, diluted and administered.The thawed MSCs with be administered within 4 hours to subjects in a monitored setting with telemetry and pulse oximetry. Patients will be premedicated with hydrocortisone and diphenhydramine. All subjects will be monitored throughout the infusion procedure with vital signs and pulse oximetry at 15 minutes prior to infusion and ending 2 hours post procedure. They will also be evaluated for clinical signs of pulmonary distress. All patients will be admitted overnight for continued observation. The patient will be examined the following day and discharged home. Intravenous infusion of 3 million allogeneic MSCs/kg In a randomized fashion, the MSCs, in the appropriate dose, will be shipped to the performance site where the MSCs will be thawed, diluted and administered.The thawed MSCs with be administered within 4 hours to subjects in a monitored setting with telemetry and pulse oximetry. Patients will be premedicated with hydrocortisone and diphenhydramine. All subjects will be monitored throughout the infusion procedure with vital signs and pulse oximetry at 15 minutes prior to infusion and ending 2 hours post procedure. They will also be evaluated for clinical signs of pulmonary distress. All patients will be admitted overnight for continued observation. The patient will be examined the following day and discharged home.
Publications *

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information
Recruitment Status † Biological
Estimated Enrollment † 36
Start Date † December 5, 2016
Completion Date June 2021
Primary Completion Date June 2020
Eligibility Criteria † Inclusion Criteria: - Be 40 and 80 years of age. - Have diagnosis of non-inflammatory degenerative infrarenal abdominal aortic aneurysms measuring 35-45 mm. in diameter by Computed Tomography (CT) scan. - 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: - Inflammatory AAA defined by a thickened aortic wall and retroperitoneal fibrosis and adhesions of peritoneal organs, and elevated erythrocyte sedimentation rate or in the opinion of investigator. - Mycotic AAA defined as saccular morphology, a positive blood culture, fever, or in the opinion of the investigator. - Symptomatic, Saccular, or any AAA associated with thoracic aorta dilatation >5.0 cm. - Infra-renal AAA associated with Marfan's or Ehlers-Danlos Syndrome or other connective tissue disorders. - Common or external iliac artery aneurysm > 30 mm. in maximal transverse diameter. - AAA due to dissection. - Allergy to iodine contrast. - History of cancer within the last 5 years, except basal cell skin carcinoma with clean border pathology report. - eGFR
Gender All
Ages 40 Years - 80 Years
Accepts Healthy Volunteers No
Contacts †† Michael P Murphy, MD BS, Michael.Murphy504b8@va.gov
Location Countries † United States
Administrative Information
NCT ID † NCT02846883
Organization ID CLNB-06-15F
Secondary IDs †† 1510579216
Responsible Party Sponsor
Study Sponsor † VA Office of Research and Development
Collaborators ††
Investigators † Principal Investigator: Michael Patrick Murphy, MD BS, Richard L. Roudebush VA Medical Center, Indianapolis, IN
Information Provided By
Verification Date February 2017
First Received Date † July 25, 2016
Last Updated Date February 9, 2017
† Required WHO trial registration data element.
†† WHO trial registration data element that is required only if it exists.
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