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

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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 50 patients with Abdominal Aortic
      Aneurysms (AAA) measuring 3-5 cm 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


Primary Outcome

Incidence of treatment related adverse events at 12 months post MSC administration as evidenced by the Investigator

Secondary Outcome

 Changes in circulating inflammatory cell phenotypes as measured by 18-FDG PET/CT

Condition

Abdominal Aortic Aneurysm

Intervention

MSC's

Study Arms / Comparison Groups

 Intravenous infusion of 1 million allogenic MSC's/Kg
Description:  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

50

Start Date

December 5, 2016

Completion Date

July 1, 2026

Primary Completion Date

June 1, 2021

Eligibility Criteria

        Inclusion Criteria:

          -  Be 40 and 85 years of age.

          -  Have diagnosis of noninflammatory degenerative infrarenal abdominal aortic aneurysms
             measuring 3-5 cm. 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 cm. 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< 30mL/min.

          -  Any condition requiring immunosuppressant medications (e.g., for treatment of organ
             transplants, psoriasis, Crohn's disease, alopecia areata, rheumatoid arthritis,
             scleroderma, lupus).

          -  Acute coronary syndrome in the last 30 days prior to enrollment.*

          -  CHF hospitalization within the last 30 days prior to enrollment.*

          -  HIV or HCV positive.

          -  Contraindication to Computed Tomography or known allergy to contrast media.

          -  Any bleeding diathesis defined as an INR 2.0 (off anticoagulation therapy) or history
             of platelet count less than 70,000 or hemophilia.

          -  Pregnant or breast feeding women.

          -  Significant hepatic dysfunction (ALT or AST greater than 2 times normal).

          -  Life expectancy less than two years.

          -  Inability to provide written informed consent due to cognitive or language barriers
             (interpreter permitted).

          -  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.
      

Gender

All

Ages

40 Years - 85 Years

Accepts Healthy Volunteers

No

Contacts

Michael Patrick Murphy, MD BS, , [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT02846883

Organization ID

CLNB-06-15F

Secondary IDs

1510579216

Responsible Party

Sponsor

Study Sponsor

VA Office of Research and Development


Study Sponsor

Michael Patrick Murphy, MD BS, Principal Investigator, Richard L. Roudebush VA Medical Center, Indianapolis, IN


Verification Date

August 2020