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

NCT02846883 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: CLNB-06-15F1510579216
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

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.

Conditions

Abdominal Aortic Aneurysm

Keywords

aneurysms; aortic aneurysm; Abdominal aortic aneurysm

Outcome Measures

Primary Outcomes (1)

• Changes in Circulating Inflammatory Cell Phenotypes as Measured by Mass Cytometry

  This trial will test the hypothesis that MSCs, in a dose dependent fashion (1 x 10\^6 MSC/kg vs 3 x 10\^6 MSC/kg) promote the frequency and immune suppressor function of Treg cells as measured by mass cytometry compared to baseline.

  12 months

Secondary Outcomes (1)

• Incidence of Treatment Related Adverse Events at 12 Months Post MSC Administration as Evidenced by the Investigator

  12 months

Study Arms (3)

Intravenous infusion of 1 million allogenic MSCs/kg

ACTIVE COMPARATOR

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.

Biological: 1 million MSCs/kg

Intravenous infusion of 3 million allogeneic MSCs/kg

ACTIVE COMPARATOR

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.

Biological: 3 million MSCs/kg

Intravenous infusion of Plasmalyte A (placebo)

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

1 million MSCs/kg BIOLOGICAL

Intravenous infusion of 1 million allogeneic MSCs/kg.

Intravenous infusion of 1 million allogenic MSCs/kg

3 million MSCs/kg BIOLOGICAL

Intravenous infusion of 3 million allogeneic MSCs/kg

Intravenous infusion of 3 million allogeneic MSCs/kg

Placebo DRUG

Intravenous infusion of Plasmalyte A (placebo)

Also known as: Plasmalyte A

Intravenous infusion of Plasmalyte A (placebo)

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

Richard L. Roudebush VA Medical Center, Indianapolis, IN

Indianapolis, Indiana, 46202-2884, United States

Location

MeSH Terms

Conditions

Aortic Aneurysm, Abdominal; Aneurysm; Aortic Aneurysm

Interventions

Plasmalyte A

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Aortic Diseases

Limitations and Caveats

The major limitation of this trial is that it did not complete enrollment of the planned 36 subjects. This is because the trial was put on hold during the COVID pandemic and when the Richard Roudebush VAMV opened for elective procedures the VA Merit grant had expired.

Results Point of Contact

• Title: Michael P. Murphy, MD
• Organization: Roudebush VA Medical Center

mipmurph@iupui.edu

317-988-4049

Study Officials

• Michael P Murphy, MD BS

  Richard L. Roudebush VA Medical Center, Indianapolis, IN

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2016
• First Posted: July 27, 2016
• Study Start: December 5, 2016
• Primary Completion: September 30, 2021
• Study Completion: September 30, 2021
• Last Updated: August 9, 2024
• Results First Posted: August 9, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)