Clinical trial NCT02846883: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Abdominal Aortic Aneurysm
Keywords: aneurysms
aortic aneurysm
Abdominal aortic aneurysm
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2016-07-27
Enrollment: 28
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.
* Estimated glomerular filtration rate (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 (ACS) in the last 30 days prior to enrollment.\*
* Congestive heart failure (CHF) hospitalization within the last 30 days prior to enrollment.\*
* HIV or Hepatitis C (HCV) positive.
* Contraindication to Computed Tomography or known allergy to contrast media.
* Any bleeding diathesis defined as an International Normalized Ratio (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 (alanine transaminase (ALT) or aspartate aminotransferase (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.

Primary outcomes:
measure: Changes in Circulating Inflammatory Cell Phenotypes as Measured by Mass Cytometry
timeFrame: 12 months
Secondary outcomes:
measure: Incidence of Treatment Related Adverse Events at 12 Months Post MSC Administration as Evidenced by the Investigator
timeFrame: 12 months
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Richard L. Roudebush VA Medical Center, Indianapolis, IN
state: Indiana
Study officials:
affiliation: Richard L. Roudebush VA Medical Center, Indianapolis, IN
name: Michael P Murphy, MD BS
role: PRINCIPAL_INVESTIGATOR
References: