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

NCT ID: NCT02846883

Last Updated: 2024-08-09

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-05
• Study Completion Date: 2021-09-30

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.

Conditions

Abdominal Aortic Aneurysm

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Intravenous infusion of 1 million allogenic 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. Subjects will be discharged 2 hours post-infusion if no signs of complications.

Group Type: ACTIVE_COMPARATOR

1 million MSCs/kg

Intervention Type: BIOLOGICAL

Intravenous infusion of 1 million allogeneic MSCs/kg.

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. Subjects will be discharged 2 hours post-infusion if no signs of complications.

Group Type: ACTIVE_COMPARATOR

3 million MSCs/kg

Intervention Type: BIOLOGICAL

Intravenous infusion of 3 million allogeneic MSCs/kg

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. Subjects will be discharged 2 hours post-infusion if no signs of complications.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Intravenous infusion of Plasmalyte A (placebo)

Interventions

1 million MSCs/kg

Intravenous infusion of 1 million allogeneic MSCs/kg.

Intervention Type: BIOLOGICAL

3 million MSCs/kg

Intravenous infusion of 3 million allogeneic MSCs/kg

Intervention Type: BIOLOGICAL

Placebo

Intravenous infusion of Plasmalyte A (placebo)

Intervention Type: DRUG

Other Intervention Names

Plasmalyte A

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.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

VA Office of Research and Development

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael P Murphy, MD BS

Role: PRINCIPAL_INVESTIGATOR

Richard L. Roudebush VA Medical Center, Indianapolis, IN

Locations

Richard L. Roudebush VA Medical Center, Indianapolis, IN

Indianapolis, Indiana, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

1510579216

Identifier Type: OTHER

Identifier Source: secondary_id

CLNB-06-15F

Identifier Type: -

Identifier Source: org_study_id

NCT02843854

Identifier Type: -

Identifier Source: nct_alias