Abdominal Aortic AneurysmPhase 1VIVAAANCT02846883
Safety and Efficacy of Allogeneic MSCs in Promoting T-regulatory Cells in Patients With Small Abdominal Aortic Aneurysms
A Phase 1 study testing 1 million MSCs/kg and 3 million MSCs/kg in people with Abdominal Aortic Aneurysm, run by VA Office of Research and Development at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 to 85 years
- Conditions the study is for
- Abdominal Aortic Aneurysm
- What is being tested?
- 1 million MSCs/kg and 3 million MSCs/kg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 28 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Dec 2016to 30 Sep 2021
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Richard L. Roudebush VA Medical Center, Indianapolis, IN
Indianapolis, Indiana, 46202-2884
About this study
Official title: Mesenchymal Stem Cells Induce Regulatory T Cells in Patients With Aortic Aneurysm
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.
Read the 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
- Being tested
- 1 million MSCs/kg, 3 million MSCs/kg, Placebo
- Keywords
- aneurysms, aortic aneurysm, Abdominal aortic aneurysm
- Medical subject headings
- Aortic Aneurysm, Abdominal, Aneurysm, Aortic Aneurysm
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
1 million MSCs/kgBiological
Intravenous infusion of 1 million allogeneic MSCs/kg.
3 million MSCs/kgBiological
Intravenous infusion of 3 million allogeneic MSCs/kg
PlaceboDrug
Also called Plasmalyte A
Intravenous infusion of Plasmalyte A (placebo)
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 months
Secondary outcomes (1)
Incidence of Treatment Related Adverse Events at 12 Months Post MSC Administration as Evidenced by the Investigator
The safety of systemic administration of allogeneic MSCs will be measured by treatment-related adverse events over a period of 12 months.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2016 (estimated)
- Study start5 Dec 2016
- Primary completion30 Sep 2021
- Study completion30 Sep 2021
Why it stopped: Early Termination as required by VA DSMB due to slow enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Abdominal Aortic AneurysmStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Michael P Murphy, MD BS, Principal investigator, Richard L. Roudebush VA Medical Center, Indianapolis, IN
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02846883
- Sponsor's protocol ID
- CLNB-06-15F
- Other IDs
- 1510579216
- Acronym
- VIVAAA
- Status last verified
- Jun 2024
- First submitted
- 25 Jul 2016
- Last updated
- 9 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mesenchymal Stem Cells Induce Regulatory T Cells in Patients With Aortic Aneurysm
- ClinicalTrials.gov ID
- NCT02846883
- Acronym / sponsor ID
- VIVAAA / CLNB-06-15F
- Conditions
- Abdominal Aortic Aneurysm
- Keywords
- aneurysms, aortic aneurysm, Abdominal aortic aneurysm
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Early Termination as required by VA DSMB due to slow enrollment
- Enrolment
- 28 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 5 Dec 2016 (actual)
- Primary completion
- 30 Sep 2021 (actual)
- Study completion
- 30 Sep 2021 (actual)
- First posted
- 27 Jul 2016 (estimated)
- Results
- Posted 9 Aug 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Intravenous infusion of 1 million allogenic MSCs/kg | Active comparator | Biological: 1 million MSCs/kgIn 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. |
| Intravenous infusion of 3 million allogeneic MSCs/kg | Active comparator | Biological: 3 million MSCs/kgIn 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. |
| Intravenous infusion of Plasmalyte A (placebo) | Placebo comparator | Drug: PlaceboIn 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. |
Who may qualify
- Ages
- 40 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (21 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 1 million MSCs/kgIntravenous infusion of 1 million allogeneic MSCs/kg. | Biological | Intravenous infusion of 1 million allogenic MSCs/kg |
| 3 million MSCs/kgIntravenous infusion of 3 million allogeneic MSCs/kg | Biological | Intravenous infusion of 3 million allogeneic MSCs/kg |
| PlaceboAlso: Plasmalyte AIntravenous infusion of Plasmalyte A (placebo) | Drug | Intravenous infusion of Plasmalyte A (placebo) |
Primary outcome
Changes in Circulating Inflammatory Cell Phenotypes as Measured by Mass Cytometry
Time frame: 12 months
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.
1 secondary outcome
Incidence of Treatment Related Adverse Events at 12 Months Post MSC Administration as Evidenced by the Investigator
Time frame: 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael P Murphy, MD BS principal investigator
Richard L. Roudebush VA Medical Center, Indianapolis, IN
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing 1 million MSCs/kg and 3 million MSCs/kg in people with Abdominal Aortic Aneurysm, run by VA Office of Research and Development at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 9 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in Circulating Inflammatory Cell Phenotypes as Measured by Mass Cytometry (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Aug 2024.