Conditions: Abdominal Aortic Aneurysm
Keywords: aneurysms aortic aneurysm Abdominal aortic aneurysm
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 28
Healthy volunteers: no

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.

Arms:
arm 1: 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. arm 2: 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. arm 3: 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.

Interventions: intervention 1: 1 million MSCs/kg intervention 2: 3 million MSCs/kg intervention 3: Placebo
Intervention descriptions: intervention 1: Intravenous infusion of 1 million allogeneic MSCs/kg. intervention 2: Intravenous infusion of 3 million allogeneic MSCs/kg intervention 3: Intravenous infusion of Plasmalyte A (placebo)

Protocol document:
Prot_SAP_000.pdf: 
Study #1510579216 
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Indiana University School of Medicine 
  
 
CLINICAL STUDY PROTOCOL 
 
 
Phase I study to examine the safety and efficacy of allogeneic MSCs in suppressing 
inflammation in patients with small abdominal aortic aneurysm (AAA)  
 
 
IRB #1510579216 
 
IND 16579 
 
Indiana University School of Medicine 
1801 N. Senate Blvd. 
MPC2, #3500 
Indianapolis, IN 46202 
 
 
July 15, 2021 
 
ETHICS AND REGULATORY COMPLIANCE STATEMENT 
The procedures set forth in this protocol are designed to ensure that the sponsor(s) and principal 
investigator(s) abide by the International Conference on Harmonization (ICH) current Good Clinical 
Practice (cGCP) guidelines, current Good Laboratory Practice (cGLP) guidelines, the Declaration of 
Helsinki, and applicable local regulatory requirements and laws in the conduct, evaluation, and 
documentation of this study. 


IRB # 1510579216      PI: Michael P. Murphy, MD 
Phase I study to examine the safety and efficacy of allogeneic MSCs in suppressing inflammation in patients with small 
abdominal aortic aneurysm (AAA)  
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Protocol Name 
Phase I study to examine the safety and efficacy of allogeneic 
MSCs in suppressing inflammation in patients with small 
abdominal aortic aneurysm (AAA) . 
Investigational Product Name 
Allogeneic mesenchymal stem cells 
Date: (dd-mmm-yyyy) 
 June 2017 
Author 
Michael P. Murphy, MD 
 
PROTOCOL HISTORY 
Date (dd-mmm-yyyy) 
Description 
7-Oct- 2015 
Response to “Clinical Hold” 
24-Mar-2016 
Remove IUH as clinical performance site 
12-May-2016 
Add 5 year long term f/u, add serum analysis 
00-July-2016 
CRC for infusion 
00-Nov-2016 
Change AAA size to 3.5-5.0  (inclusion criteria) 
22-Nov-2016 
Add Day 14 f/u +/- 5 days to schedule  
06-Dec-2016 
Corrections to the f/u schedule 
29-Dec-2016 
Add HLA typing, remove temp log, PET CT: add month 12, change Mo 1 
to a range of 2-6 weeks, add agent orange exposure to data capture. 
03-JAN-2017 
Removed Obstructive Sleep Apnea from exclusion, Removed month 18 
& 14 labs and ECG’s Removed infectious disease labs (except HIV and 
Hep. C) from baseline testing. Decreased the number and amount of 
blood specimens obtained. 
April-2017 
$30 stipend added for travel reimbursement 
May-2017 
AAA size from 3.5 to 3.0. Remove Pet CT’s. CT at baseline and 12-month 
f/u.  
July-2017 
Remove f/u HbA1C’s, remove all direct bilirubin tests, add: Karen Lynn 
& Ashley Gutwein. Increase peripheral blood draws for ancillary studies 
to 34 ml. 
Sept.-2017 
Remove open label statements, replace with double blind. Remove 
overnight stay. Complete ECG and labs on day 3. Add Day 1 phone call. 
Remove use of home oxygen from exclusion. Add Month 12 QoL 
questionnaires to the follow-up schedule. Remove ICS contact info. 
Dec-2017 
Increase the age of subjects from 80 to 85 in the inclusion criteria. 
Remove the physical exams to be completed by the PI from Months 6, 
12, 18 & 24. 
Jan-2018 
Adding Janet Klein and Dr. Dalsing. Adding Methodist Hospital and the 
CRC as performance sites.  
February 2018 
Change MSC cell manufacturing source to Case Western Reserve 
University in Cleveland, Ohio, and/or Longeveron, LLC in Miami, Florida.   
05 JUN 2018 
Remove the Day 3 ECG. Page 15: changed the age to 85 (this was 
changed 1.4.18). 
27 JUN 2018 
Remove Day 3 from the Follow-Up schedule. 
 
 
18 JUL 2018 
 
Clarification of (6.1.3 page 17) MSC handling, storage and 
accountability. Remove Longeveron, LLC, add Tiffany Liang, remove 
Keisin Wang and Linden Green.  Re-enter omitted ECG, CTA, and U/S 


IRB # 1510579216      PI: Michael P. Murphy, MD 
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abdominal aortic aneurysm (AAA)  
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tests into schedule of events from previous AMD clerical error. This is 
not new testing. 
20 SEP 2018 
Remove baseline CT and replace with (previous) PET CT and again at 
Day 14. SOC CTA at month 12 to remain. Replace the Month 6 QoL 
Questionnaire on the Follow up schedule (protocol & ICS). 
22 APR 2019 
Inpatient stay after study product infusion changed from 4 hours to 2 
hours. All subjects (VA & IUH) will receive a $30 gift card for the first 5 
study visits, no mileage requirement. Patients will be reexamined 
changed from day 3 & 7 to days 7 & 14. 
15 JUL 2021 
Add unblinding of subjects at Month 24 follow-up visit.  Add off-site 
storage of VA specimens to SSF (VA HIPAA Auth).  Remove Maryanne 
Bowyer-Cherry. 
 
 
 
 
 
CONTACT INFORMATION 
 
Sponsor: 
Indiana University School of Medicine 
Primary Study Contact, Principal 
Investigator: 
 
Michael P. Murphy, MD 
 
 
 
Protocol Author: Michael P. Murphy, MD 
 
 
Coordinating Investigator and Principal Investigators   
An updated list of Principal Investigators (PI), investigation sites, and institutions will be 
maintained separately. The definitive list will be provided in the clinical study report. 
 


IRB # 1510579216      PI: Michael P. Murphy, MD 
Phase I study to examine the safety and efficacy of allogeneic MSCs in suppressing inflammation in patients with small 
abdominal aortic aneurysm (AAA)  
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PROTOCOL SIGNATURE PAGE 
 
 
 
Phase I study to examine the safety and efficacy of allogeneic MSCs in suppressing inflammation in 
patients with small abdominal aortic aneurysm (AAA)  
 
 
 
As an Investigator for this Study, I have read the Clinical Trial Protocol. I agree to make available to the 
Sponsor, Indiana University School of Medicine (or its designee), original source documents and all 
regulatory documents pertaining to this Study. I agree to cooperate fully with the Sponsor with the 
conduct of study-related audits. 
 
By my signature below, I agree to conduct this Study in accordance with the Clinical Trial Protocol, 
current Good Clinical Practice (cGCP) and Good Laboratory Practice (cGLP) guidelines, obligations as 
set forth in Title 21 CFR Parts 812, 54, 5,6 and 11 (as applicable), and any applicable regulatory laws. 
I will make no changes to protocol-defined procedures without written permission from the Sponsor.   
 
I understand that Investigational Use Products may be used only for the purposes explicitly described in 
this protocol.  
 
I further agree to treat the results of this Study as confidential information and will not submit the results 
of the Study for publication without prior written authorization from the Sponsor.  
 
 
 
Michael P. Murphy, MD 
  
 
7/15/2021 
PRINTED NAME 
 SIGNATURE  
DATE 
 
 


IRB # 1510579216      PI: Michael P. Murphy, MD 
Phase I study to examine the safety and efficacy of allogeneic MSCs in suppressing inflammation in patients with small 
abdominal aortic aneurysm (AAA)  
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SYNOPSIS 
Title of Study 
Phase I study to examine the safety and efficacy of allogeneic MSCs in 
suppressing inflammation in patients with small abdominal aortic 
aneurysm (AAA) 
Objectives 
 
Assess the safety and efficacy of systemic (IV) administration of 
escalating doses of allogeneic MSCs in modulating immune cell 
phenotypes and suppressing aortic inflammation in patients with small 
AAA.  
Planned Number of 
Subjects and Duration of 
Involvement 
 36 patients  
Patient Population 
 
Abdominal aortic aneurysms (AAA) patients 
Investigational Product 
Name 
Allogeneic mesenchymal stem cells  
Methodology Overview 
 
In a double blind, Phase I trial, 36 patients with AAA measuring 30-
50mm in maximal transverse diameter (MTD) will be randomized in a 
1:1:1 fashion to receive either 1.0 x106 MSCs/kg (n=12), 3.0 x106 
MSCs/kg. (n=12), or placebo (Plasmalyte A) (n=12) delivered 
intravenously. The primary safety endpoints will be incidence of 
treatment related adverse events at 24 months post MSC-
administration. Exploratory primary efficacy endpoints will be changes 
in circulating inflammatory cell phenotypes and aortic inflammation as 
measured by CT. The treatment period will involve long-term follow-up 
through 5 years.  The incidence of surgical intervention, aneurysm 
related death, quality of life, and major adverse cardiac events will be 
recorded. 
 
 
 


IRB # 1510579216      PI: Michael P. Murphy, MD 
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Table 1 
Abbreviations 
AAA 
Abdominal Aortic Aneurysm 
AE 
Adverse Event 
AMI 
Acute Myocardial Infarction 
ASC 
Adipose derived MSC 
bMSC 
Bone marrow derived MSC 
CTSI 
Clinical and Translational Sciences Institute 
DSMB 
Data Safety Monitoring Board 
eGFR 
Effective Glomerular Filtration Rate 
GVHD 
Graft Versus Host Disease 
IFN-γ 
Interferon-γ, 
IL 
Interleukin 
IND 
Investigational  New Drug Application 
IV 
Intravenous delivery 
MACE 
Major Adverse Cardiac Event 
LC-MS 
Liquid chromatography-mass spectrometry 
MCP-1 
Monocyte Chemotactic Protein-1 
MLR 
Mixed Lymphocyte Reaction 
MMP 
Matrix Metalloproteinases 
MNC 
Mononuclear cell 
MSC 
Mesenchymal Stromal Cell 
pMSC 
Placenta derived MSC 
18-FDG PET/CT 
18-florodeoxyglucose positron emission 
tomography/computed tomography 
RANTES 
Regulated on Activation,  
Normal T cell Expressed and Secreted 
SAE 
Serious Adverse Event 
TIMP 
Tissue Inhibitors of Metalloproteinases 
TNF-α 
Tumor Necrosis Factor-α, 
Treg 
T regulatory cell 
TSG-6 
TNF- secreted protein 6 
VAMC 
Veterans Administration Medical Center 
WBC 
White Blood Cell Count 


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TABLE OF CONTENTS 
 
2. INTRODUCTION. ........................................................................................................................................ 9 
3. DESCRIPTION OF THE INVESTIGATIONAL PRODUCT ................................................................................. 9 
3.1 Overview ............................................................................................................................................. 9 
3.2   Preclinical Data ................................................................................................................................ 10 
3.3 Proposed Intended Use Statement ................................................................................................. 140 
    3.4 Study Objectives ................................................................................................................................ 15 
4.0 STUDY OVERVIEW ................................................................................................................................. 15 
4.2 Study Approach ................................................................................................................................. 15 
4.3 Study Duration .................................................................................................................................. 15 
5. STUDY POPULATION ............................................................................................................................... 15 
5.1 Sample Size and Target Study Population ........................................................................................ 15 
5.1.1 Sample size ................................................................................................................................. 15 
5.1.2 Study population ........................................................................................................................ 15 
5.1.3 Alignment with intended study population ............................................................................... 15 
5.2 Recruitment Methods ....................................................................................................................... 16 
5.2.1 Recruitment for Study ................................................................................................................ 16 
5.2.2 Duration of Study Activities ....................................................................................................... 16 
6. STUDY MATERIALS .................................................................................................................................. 17 
6.1 Investigational Product ..................................................................................................................... 17 
6.1.1 Identity of the Investigational Product ...................................................................................... 17 
6.1.3 Handling, Storage, Accountability .............................................................................................. 17 
6.1.5 External Studies ......................................................................................................................... 18 
6.2 Other Study Materials ....................................................................................................................... 18 
6.2.1 Materials to be Provided by Study Site ...................................................................................... 18 
6.2.2 Materials to be Provided by External Testing Facilities ............................................................. 18 
7. STUDY PROCEDURES ............................................................................................................................... 19 
7.1 Workflow ........................................................................................................................................... 20 
Table 3. Long-Term Follow-Up Schedule ................................................................................................ 22 
7.2 Study Data ....................................................................................................................................... 223 
7.2.1 Collection of data ....................................................................................................................... 22 


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7.3 Procedures for Study Closure ........................................................................................................... 22 
7.3.1 Routine Study Close-out ............................................................................................................ 22 
7.3.2 Suspension or Premature Termination of the Study ................................................................. 22 
8. DATA QUALITY ASSURANCE .................................................................................................................... 23 
9. STATISTICAL METHODS ......................................................................................................................... 234 
9.1 Bias Minimization .............................................................................................................................. 23 
9.2 Planned Analyses .............................................................................................................................. 23 
10. ADVERSE EVENT REPORTING ................................................................................................................ 24 
10.1 Adverse Events and Stopping Rules ................................................................................................ 24 
10.2 Sponsor Contact for Serious Adverse Event Reporting................................................................... 25 
11. RISK ANALYSIS ..................................................................................................................................... 256 
11.1 Potential Risks of the Investigational Product and Clinical Investigation ....................................... 25 
11.2 Potential Benefits of the Investigational Product and Clinical Investigation .................................. 25 
11.3 Minimization of Risks ...................................................................................................................... 25 
12. INVESTIGATOR RESPONSIBILITIES ......................................................................................................... 26 
12.1 Site Qualification and Study Oversight ........................................................................................... 26 
12.2 Case Report Forms/Electronic Data Records .................................................................................. 26 
12.3 Access to Source Documents .......................................................................................................... 26 
12.4 Financial Disclosure ......................................................................................................................... 27 
12.5 Deviations from the Study Protocol ................................................................................................ 27 
12.6 Record Retention ............................................................................................................................ 27 
12.7 Publication Policy ............................................................................................................................ 27 
13. ETHICS AND COMPLIANCE .................................................................................................................... 27 
13.1 Informed Consent and De-Identification ........................................................................................ 27 
13.1.1 Prospectively Collected Data ................................................................................................... 27 
13.2 IRB Review....................................................................................................................................... 28 
13.3 Confidentiality of Data and Patient Records ................................................................................... 28 
13.3.1 Provisions to Protect the Privacy Interests of Participants ...................................................... 28 
14. REFERENCES ........................................................................................................................................ 289 
 
 
 


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2. INTRODUCTION. 
Each year 200,000 people are diagnosed with AAA in the U.S. and 15,000 will inevitably die from rupture.1 
Approximately 39,000 endovascular or open surgeries are performed annually to prevent complications 
of AAA with two-year costs of $105,745 and $108,344 (2012 U.S. dollars), respectively.2 The risk of rupture 
accelerates with AAA diameter thus an effective therapy that could mitigate AAA expansion would have 
a significant impact on patient survival, quality of life, and health care costs. In a recent randomized, 
placebo-controlled trial; doxycycline, an inhibitor of a key protease implicated in AAA formation, matrix 
metalloproteinase-9 (MMP), failed to reduce AAA expansion.3 The pathogenesis of AAA begins with early 
T-cell and macrophage activation with subsequent recruitment of neutrophils and activation of MMPs.1 
The result is smooth muscle cell apoptosis, elastin degradation, and loss of structural integrity of the aortic 
wall. Extinguishing this inflammatory cascade in its initiation may prove more effective than targeting later 
phase proteases. 
 
Mesenchymal stromal cells (MSC) have pleiotropic immunomodulatory properties relevant to the 
pathogenesis of AAA.4,5 Our laboratory has shown that MSCs induce formation of immunosuppressive T-
regulatory cells, decrease cytotoxic CD28-T cells, promote polarization of macrophages to the anti-
inflammatory M2 phenotype, and inhibit neutrophil infiltration. Furthermore, human MSCs delivered 
intra-venously significantly decreased AAA inflammation and expansion in murine models, evidence that 
MSCs warrant further evaluation for this purpose in the context of a clinical trial.6 
 
The objective of this study is to conduct a single center, double blind, Phase I trial to test the safety of 
systemic (intravenous, IV) administration of allogeneic bone marrow derived MSCs and compare two 
doses (1 million and 3 million MSCs/kg. in modulating inflammatory responses in patients with small AAA. 
The rationale for this investigation is: (1), there are no effective treatment options that suppress AAA 
inflammation and expansion; (2), there is an established safety profile of MSCs in previous clinical trials7-
11; and (3), compelling preliminary data supporting this concept.  
 
3. DESCRIPTION OF THE INVESTIGATIONAL PRODUCT  
3.1 Overview  
Human bone marrow derived MSCs increase T- regulatory (Treg) cells and decrease CD4+ and CD8+ 
cytotoxic T-cells in co-culture with peripheral blood mononuclear cells collected from AAA patients. 
Furthermore, we have demonstrated that human MSCs increase Tregs in blood and aortic tissue in mouse 
models of AAA while significantly decreasing aneurysm expansion. Treg induction presents a novel 
approach that may clinically suppress the inflammatory processes pathogenic in AAA formation. 
 
3.2   Preclinical Data using adult human allogeneic bone marrow derived MSCs to support this IND. 
     3.2.1 The allogeneic MSCs used for these experiments are provided by Case Western Reserve 
University in Cleveland, Ohio. MSCs were obtained from 50 mL of bone marrow aspirated from a young, 
healthy donor. Mononuclear cells were cultured in 175 cm2 flasks. Adherent cells were harvested and 
passaged (P1) into new flasks and at 70-80% confluence, they were further expanded to a second passage 
only (P2). MSCs used in these preclinical studies were manufactured using the exact processes that will 
be used for the MSCs to be used in the clinical trial detailed in this IND, thus we expect that MSC potency 
will be equivalent. 
 
     3.2.2 Circulating CD4+FoxP3+ T-regulatory cells are decreased in patients with AAA and significantly 
increased after co-culture with Human MSCs. PBMC specimens were isolated from patients undergoing 
endovascular AAA repair (n=10) and healthy subjects (n=5) and were stained with fluorochrome labeled 


IRB # 1510579216      PI: Michael P. Murphy, MD 
Phase I study to examine the safety and efficacy of allogeneic MSCs in suppressing inflammation in patients with small 
abdominal aortic aneurysm (AAA)  
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antibodies for CD3, CD4, CD25, and after permeabilization, for FoxP3, as previously decribed.9 We found 
that there were significantly fewer circulating Treg cells in AAA patients (0.46 ± 0.07%) as compared to 
healthy controls (0.67+0.16%, P=0.01), (Fig.1A).  PBMCs from AAA patients were then co-cultured with 
MSCs or saline for 7 Days and Treg were then quantified with FACS. MSCs significantly increased Treg at 
7 days compared to control (2.56+0.06% vs. 1.07+0.04%, P< 0.01) (Fig. 1B, C). 
 
 
     
 3.2.3 Human MSCs increase T-regulatory cells in aortic aneurysm tissue in the mouse elastase AAA model. 
C57Bl/6 mice were given hMSCs (1x106) or PBS 24 hours after aortic elastase perfusion. Mice were 
sacrificed at Days 1, 4, and 7 and aortas harvested. Immunohistochemical (IHC) staining of aneurysm 
sections (Fig. 2A) demonstrated that hMSCs significantly increased murine Treg as compared to controls 
at each time point (Fig. 2B). 
 
 
     3.2.4 Human MSCs increase immune suppressor function in the mouse elastase AAA model. Using the 
murine elastase AAA model, 1x106 human MSCs or phosphate buffered saline (control) were injected IV 
(n=5/group) at the time of elastase application. At 72 hours the mice were sacrificed and CD4+CD25+ cells 
were isolated from PBMC using magnetic beads followed by cell sorting to isolate Tregs 


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(CD4+CD25+CD127lo) and CD4+CD25+ T-cells (responder cells) . The cells were cultured in varying ratios: 
Treg: Tresponder of 0.1:1.0; 0.5:1.0; and 1:1, in 96 well culture plates coated with 100 μL of 5.0 μg/mL 
anti-CD3 and anti-CD28. Controls were the CD4+CD25− responder cells plated alone. Cell proliferation was 
measured using a modified 3-[4,5-dimethyl-2-thiazol-yl]-2,5-diphenyltetrazolium bromide assay with a 
Premix WST-1 Cell Proliferation Assay System as described. Percentage suppression was determined at 
each ratio of Treg: Tresp by comparison with CD4+CD25− cells (Tresp) plated alone. We found that 
immunosuppressive activity was significantly increased in Tregs from MSC treated compared to control 
treated mice (Fig. 3).  
 
 
 
     3.2.5 Circulating CD4+CD28- and CD8+CD28- T-cells are increased in patients with AAA and significantly 
decreased after human MSC infusion in the murine elastase AAA model. The mononuclear cell fraction of 
peripheral blood (PBMC) was isolated from patients with AAA and age matched healthy subjects and 
analyzed with FACS. Percentages of CD4+CD28- and CD8+CD28- T-cells were significantly greater in AAA 
patients compared with healthy controls. Adjusting for normal accumulation of CD28− T cells in healthy 
controls, 60.4% of the AAA patients had elevated levels of CD4+CD28− T cells and 19.8% showed increased 
levels of CD8+CD28− T cells in the peripheral blood (Fig.4 A). MSCs or phosphate buffered saline (PBS) were 
infused in C57Bl6 mice at the time of AAA induction. CD4+CD28- and CD8+CD28- T-cells and Neutrophils 
(Ly6G/C+) from aortic aneurysm tissue specimens were quantified using flow cytometry at Day 7 after MSC 
or PBS infusion revealing a significant decrease in all of these pathogenic inflammatory cell phenotypes 
(Fig.4B).  
 
 
 


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     3.2.6 Human MSCs preserve elastin and collagen and inhibit matrix metalloproteinase-9 activity in the 
murine elastase AAA model. Using the topical elastase AAA model, we performed histological 
comparisons of the aneurysmal tissue to assess the effects of MSCs on elastin and collagen fiber content 
in the extra-cellular matrix of the aortic wall. We found that compared to control mice, MSC treated mice 
retained elastin lamellae and collagen fibers (Fig. 5A-C). Elastin is the primary architectural protein of the 
aorta and is destroyed by production of MMP-9 by activated inflammatory cells leading to loss of tensile 
strength and aneurysm formation. MMP-9 serum levels are elevated in about 50-70% of patients with 
AAA. MSCs have been shown to secrete tissue inhibitors of metalloproteinsase-1 and -2 that inhibit MMP-
2 and -9 activity in vitro. We found that compared to control treated AAA mice, MSCs significantly 
decrease serum MMP-9 activity (Fig. 5D). 
 
 
 
     3.2.7 Systemic infusion of human MSCs suppresses IL-17, -23, and IFN-γ and AAA expansion in the 
mouse elastase model. We delivered hMSC IV on day 1 after perfusion of the aorta with elastase. We then 
measured aortic diameter by video micrometry at Day 14. Compared to baseline, aortic diameter was 
significantly decreased in hMSC-treated compared with saline treated mice (Fig. 6A). 
 
 


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     3.2.8 IL-10 responses are deficient in AAA patients and  robustly enhanced after MSC administration in 
vivo in the murine elastase AAA model. Serum levels of the anti-inflammatory cytokine IL-10 are 
significantly decreased in patients with AAA as compared to risk factor matched subjects without AAA , 
whereas as serum levels of TSG-6 and PGE2 are increased in AAA patients. This suggests that an impaired 
host IL-10 response to tissue injury and inflammation may contribute to AAA formation (Fig. 7). Clinical 
grade MSCs exposed to TNF-α in culture robustly secreted 12x the levels of IL-10, 7.6x levels of TSG-6, 3.6x 
levels PGE2, and 1.6x levels of TGF-β from unstimulated conditions (Fig. 8A). Using the same MSC stock 
we then administered 1x106 cells to our mouse AAA model. Using species specific antibodies for human 
and mouse IL-10 we discovered that mouse serum levels of human IL-10 peaked at Day 3 and then were 
undetectable by Day 7. Serum levels of mouse IL-10 were significantly increased at Day 7 and continued 
to increase to Day 21 (when the experiment was terminated) in MSC treated treated AAA mice (Fig. 8B). 
Thus it appears that MSCs induce a delayed endogenous host IL-10 response that may sustain the anti-
inflammatory effect after human MSCs are cleared. Tr1 regulatory cells are induced by exogenous IL-10 
and exert immunoregulatory control via secretion of IL-10. Thus we plan to enumerate Tr1 in addition to 
FoxP3+ Tregulatory cells in Aim 1 of this proposal. 
 
 
Figure 6. Human bone marrow MSCs attenuate AAA expansion in the murine elastase model.  MSCs 
significantly suppressed murine elastase induced aortic expansion by day 4 compared to vehicle (A). Mouse 
aorta ultrasound images of at baseline and days 4, 7 and 14 post elastase treatment or 1 x 106 human MSCs 
(i.v.) (B). N=4-10/group, **p<0.01. 


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3.3 Proposed Intended Use Statement 
Allogeneic MSCs are a novel therapeutic option to suppress growth of small AAA. Human MSCs are 
intended for investigational use only by selected investigators familiar with their use and experienced in 
conducting clinical studies. Human MSCs may only be administered to human subjects participating in 
clinical studies sponsored/approved by Indiana University School of Medicine, and who have provided 
formal written consent.  
 
 
 
 
Figure 7. IL-10 is deficient in patients 
with AAA.  Blood samples were 
collected from patients being screened 
AAA. Using the Bio-plex multi-analyte 
system we found significant differences 
in, IL-10 (14.36 ± 0.51 vs. 8.03 ± 1.01), 
IL-17a (9.00 ± 4.16 vs. 67.82 +/32.93), 
IFN-γ (3.22 ± 1.69 vs. 40.63 ±17.66), 
TNF-α (5.14± 1.84 vs. 8.32 ± 0.99), 
PGE2 (54.3 ± 21.02 vs. 176.69 ± 43.1), 
and TSG-6 (545.8 ± 358 vs. 9826.53 
±1280), pg./ml; non-AAA vs. AAA, 
respectively, P< 0.01 
Figure 8. Mesenchymal Stromal Cells robustly secrete IL-10 in vitro and induce an endogenous IL-10 response 
in vivo.  MSCs were cultured to 90% confluency and 10ng/ml of TNF-α was added. After 24 hours the supernatant was 
collected and analyzed by ELISA. IL-10 increased from 1.12 ± 0.31 to 13.23 ± 0.25 pg/ml, TGF-β ↑ 148.08±11.29 to 
245.12±19.74 pg/ml., PGE2 ↑from 704.12±21.2 to 2586.52±142.69 ng. /ml., and TSG-6 ↑from 1474.82 ±11.41 to 
11276.06 ±1802.06 ng. /ml.(±SEM) (A). Using our murine elastase model we administered 1 x106 human MSCs after 
AAA induction and peripheral blood (n=5/per time point) was collected. Using ELISA with species specific antibodies 
we found that there was an initial surge of human IL-10 peaking at Day 3 (25.59 ± 11.11 pg./ml) and undetectable at 
Day 7. Murine IL-10 significantly increased at Day 7 (148.63 ± 23.62 SEM pg./ml) in MSC treated mice vs. control 
(73.71± 12.02 pg./ml.)  and peaked at Day 21 (426.28 ± 21.52 pg./ml) vs. control (69.21±19 pg./ml), when the 
experiment was terminated. (±SEM) * P< 0.05, **P<0.01, and ***P< 0.001 compared to control (B). 


IRB # 1510579216      PI: Michael P. Murphy, MD 
Phase I study to examine the safety and efficacy of allogeneic MSCs in suppressing inflammation in patients with small 
abdominal aortic aneurysm (AAA)  
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3.4 Study Objectives. 
The principal objective of this study is as follows: 
Assess the safety and efficacy of administration of allogeneic MSCs in patients with small AAA.  
This study will test the hypothesis that administration of MSCs in doses of 1x 106 MSCs/kg. and 3x 106 
MSCs/kg demonstrate safety in patients with small AAA. This trial will also test the hypothesis that MSCs, 
in a dose dependent fashion (1 x106 MSC/kg. vs. 3.0 x 106 MSC/kg.), promote the frequency and immune 
suppressor function of Treg cells and decrease AAA inflammation as measured by computed tomography. 
In an double blinded, Phase I trial, 36 patients with AAA measuring 35-50 mm in maximal transverse 
diameter (MTD) will be randomized in a 1:1:1 fashion to receive intra-venously either a single dose of 1 
x106 MSCs/kg., 3 x106 MSCs/kg. , or placebo (Plasmalyte A) (n =12/group). 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 PET 
CT compared to baseline. Secondary endpoints measured out to year 5 will include changes in IL-10 and 
Tr1 levels.  Duplex ultrasound measurements of the AAA, which is considered standard of care, will be 
recorded as change in aortic inflammation during long-term follow-up.  Incidence of surgical intervention, 
aneurysm related death, quality of life, and major adverse cardiac events will be recorded through year 
five (5).  
 
Completion of this study will determine if MSCs are safe in patients with AAA and provide critical insights 
that will direct a placebo-controlled, Phase II randomized trial.  
 
4.0 STUDY OVERVIEW 
4.2 Study Approach 
This protocol is designed to describe a Phase I single center, double blind study that will enroll 36 patients 
having a diagnosis of degenerative infrarenal abdominal aortic aneurysms measuring 35-50 mm. in 
diameter by Computed Tomographic imaging. The PI, Michael P. Murphy MD will be unblinded. Co- 
Investigators, nurse coordinators and study subjects will be blinded.  At Month 24 post-study product 
infusion, subjects will have the option to be unblinded to their investigational product. 
 
4.3 Study Duration 
It is expected that the study will be completed within 8 years.  Each patient will be followed for 24 months 
for assessment of safety with long-term follow-up through year 5 after enrollment.  
 
5. STUDY POPULATION 
5.1 Sample Size and Target Study Population 
5.1.1 Sample size 
The total number of individual subjects is expected to reach up to 36.   
5.1.2 Study population  
The study population will be representative of adults at least 40 years of age and at most 85 years of age 
with small (30-50mm) AAA. Children will not be eligible for this study because AAA is a degenerative and 
inflammatory disease of the aged. It is anticipated that at minimum, enrollment will reach approximately 
1-16 qualifying adults per month for 1–2 years.  
5.1.3 Alignment with intended study population  
The study population includes patients likely to benefit from allogeneic MSC transplantation. It will also 
include other patients who will be controls. 
 


IRB # 1510579216      PI: Michael P. Murphy, MD 
Phase I study to examine the safety and efficacy of allogeneic MSCs in suppressing inflammation in patients with small 
abdominal aortic aneurysm (AAA)  
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5.2 Recruitment Methods 
5.2.1 Recruitment for Study 
Eligible patients will be invited to participate in the study on a first-come basis, subject to Indiana 
University School of Medicine weekly recruitment goals. Patients will be recruited for this study from the 
Richard Roudebush VA Medical Center and IU Health Methodist Hospital. Patients will be informed of the 
possible risks of the procedure and will be required to give informed consent before study-specific 
procedures can proceed. A minimal financial inducement will not be offered. Each subject will be informed 
that no personally relevant clinical information will be derived from the collected data, and that the only 
possible benefit to the subject is a decrease in AAA expansion rates. Medications will be documented and 
certain medications may be held. Each subject’s involvement in the study will be limited to the period 
between signing of the informed consent form (ICF) and the completion of study specific procedures.   
5.2.2 Duration of study activities 
Enrollment is anticipated to continue for approximately 1–2 years. In the event that additional studies 
are going to be conducted, new protocols will be developed specifically for those studies. 
 
5.3 Patient Selection. The eligibility criteria for prospective enrollment of subjects are shown in Table 1.  
Inclusion criteria 
1. Be ≥ 40 and ≤85 years of age.  
2. Have diagnosis of non-inflammatory degenerative infrarenal abdominal aortic 
aneurysms measuring 30-50mm. in diameter by Computed Tomography (CT) 
scan.  
3. 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 
1. 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. 
2. Mycotic AAA defined as saccular morphology, a positive blood culture, fever, or 
in the opinion of the investigator. 
3. Symptomatic, Saccular, or any AAA associated with thoracic aorta dilatation > 
5.0 cm. 
4. Infra-renal AAA associated with Marfan’s or Ehlers-Danlos Syndrome or other 
connective tissue disorders 
5. Common or external iliac artery aneurysm > 30 mm. in maximal transverse 
diameter. 
6. AAA due to dissection. 
7. Allergy to iodine contrast. 
8. History of untreated or recurrent cancer within the last 5 years, except basal cell 
skin carcinoma.  
Table 1. 
Inclusion/Exclusion Criteria for Enrollment of Subjects  


IRB # 1510579216      PI: Michael P. Murphy, MD 
Phase I study to examine the safety and efficacy of allogeneic MSCs in suppressing inflammation in patients with small 
abdominal aortic aneurysm (AAA)  
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6. STUDY MATERIALS 
6.1 Investigational Product 
     6.1.1 Identity of the investigational product  
The clinical grade allogeneic MSCs required for this Phase I study will be provided by the Case Western 
Reserve University in Cleveland, Ohio. MSCs will be cultured from mononuclear cells obtained from a 
single healthy donor and expanded to passage 2.  
 
     6.1.2 Safety issues 
Enrolled patients will be randomized to receive 1 or 3 million MSC/kg or placebo IV. This dose has been 
extrapolated from our preclinical model6 and spans the range of MSC doses used in previous clinical 
trials.7-11 Hare, et al, tested the safety of allogeneic MSCs in patients with acute myocardial infarction 
randomized to doses of 0.5, 1.6, and 5 million MSCs/kg in a similar dose escalation study without 
treatment related adverse events. 
 
     6.1.3 Handling, storage, accountability 
MSCs will be transported using a liquid nitrogen dry shipper validated for 4 days to maintain temperature 
for long-term storage.  The temperature is logged upon arrival and becomes part of the official shipping 
documentation.  The integrity and temperature of the cell containers are checked on arrival and results 
documented. The study product should not be at room temperature for more than four hours. 
  
     6.1.4 Required training and MSC administration 
MSCs will be manufactured at the Case Cancer Comprehensive Center Cellular Therapy Lab at Case 
Western Reserve University in Cleveland, Ohio with supervised and trained personnel. The MSCs, in the 
9. eGFR< 30mL/min. 
10. Any condition requiring immunosuppressant medications (e.g., for treatment of 
organ transplants, psoriasis, Crohn’s disease, alopecia areata, rheumatoid 
arthritis, scleroderma, lupus). 
11. Acute coronary syndrome in the last 30 days prior to enrollment. * 
12. CHF hospitalization within the last 30 days prior to enrollment. * 
13. HIV or HCV positive. 
14. Contraindication to Computed Tomography or known allergy to contrast media. 
15. Any bleeding diathesis defined as an INR ≥ 2.0 (off anticoagulation therapy) or 
history of platelet count less than 70,000 or hemophilia. 
16. Pregnant or breast feeding women. 
17. Significant hepatic dysfunction (ALT or AST greater than 2 times normal). 
18. Life expectancy less than two years. 
19. Inability to provide written informed consent due to cognitive or language 
barriers (interpreter permitted). 
20. 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. 
Participant 
Withdrawal Criteria 
At the discretion of the investigator or at the request of the participant. The reason 
for withdrawal will be documented, specifically if the reason is due to an adverse 
event. 


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Phase I study to examine the safety and efficacy of allogeneic MSCs in suppressing inflammation in patients with small 
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appropriate dose, will be shipped to the Cell Therapy Laboratory at University Hospital where the MSCs 
will be thawed and diluted 1:1 with Plasmalyte A and administered within 4 hours of the thawing process. 
All personnel in the Stem Cell Laboratory are qualified in the processing on MSCs for patient 
administration. The thawed MSCs will then be administered to the patients in a monitored setting with 
telemetry and pulse oximetry.  
MSC Administration. This is a randomized, double blinded trial and after enrollment, patients will be 
randomized in a 1:1:1 fashion to receive placebo (Plasmalyte A), 1x106 MSC/kg., or 3 x 106 MSC/kg. The 
rationale for selection of these doses was presented in the Research Strategy. IV MSC infusions will occur 
in a monitored inpatient room on the Surgical Intensive Care Unit at the Roudebush VA Hospital or the 
Clinical Research Center at IU Health University Hospital. Patients will be pre-medicated with 
hydrocortisone (25-50 mg. IV) and diphenhydramine (Benadryl, 25-50 mg. IV).  All subjects will be 
monitored throughout the MSC infusion procedure with vital signs and pulse oximetry beginning 15 
minutes prior to infusion and ending 2 hours post procedure.  They will also be evaluated for clinical signs 
of pulmonary distress including progressive or sustained hypoxia, dyspnea, and tachycardia. If enrolled 
patients develop any of the following conditions within 24 hours of planned infusion, MSC delivery will be 
halted: 
a. Fever (Temperature increase to ≥100.4oF) 
b. Upper respiratory tract infection diagnosed by independent health provider. 
c. Significant shortness of breath 
d. Unanticipated change in consciousness or neurological change 
e. Major adverse cardiac event  
 
All patients will be admitted for continued observation to the SICU at the Roudebush VA Hospital or the 
Clinical Research Center at IU Health University Hospital. The patient will be observed for two hours after 
the study product infusion and then discharged home. The patient will be re-examined on Days 7 and 14 
for treatment related adverse events.  
 
6.1.5 External studies 
In the event that plans are made to conduct additional studies, new protocols describing the relevant 
handling, storage, accountability, and training procedures will be prepared specifically for those studies.  
 
6.2 Other Study Materials 
6.2.1 Materials to be provided by study site 
• 
Study notebooks to maintain study documents, including signed ICFs, all applicable information, 
and additional forms to be collected and retained by the study institution during the course of the 
study.  
• 
Example spreadsheets for tracking patient information. 
 
6.2.2 Materials to be provided by external testing facilities  
There are no external testing facilities associated with this study. 
 


IRB # 1510579216      PI: Michael P. Murphy, MD 
Phase I study to examine the safety and efficacy of allogeneic MSCs in suppressing inflammation in patients with small 
abdominal aortic aneurysm (AAA)  
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7. STUDY PROCEDURES 
7.1 Workflow  
MSC preparation.  Donor infectious disease testing will be performed by CLIA certified Laboratories.  
Allogeneic donor Infectious Diseases testing will include anti-HIV-1/2 and anti-HCV. Testing will be 
repeated if it exceeds 30 days.  Potential donors whose testing is incomplete or not available within 30 
days will not be eligible to donate bone marrow and testing will be repeated to confirm ID markers.  
Potential donors testing positive for any of these infectious diseases will NOT be eligible.  
Randomization Scheme and MSC Dosing. The PI, Michael P. Murphy MD., will determine inclusion in the 
study. After that decision has been rendered, the patient will be screened for enrollment. After 
enrollment, 36 patients will be randomized to receive MSCs or placebo IV through an antecubital vein 
(Figure 1).  
 
 
 
 
Serum samples will be collected pre-MSC administration, 1 and 6 months’ post MSC-treatment and 
analyzed in the Cellular Therapy Laboratory of University Hospital to determine if patients develop 
antibodies against allogeneic MSCs. 
 
 
Baseline Screening and Follow-Up Schedule. The following evaluations will be carried out at baseline to 
determine if patient is eligible for study: (1) Baseline blood tests (complete blood count, serum 
chemistries and liver panel); (2) infectious disease panel and HLA typing; (3) medical history and physical 
exam; (4) concomitant medications; (5) pregnancy test for women of childbearing age ;(6)12 lead ECG; (7) 
18-fluorodeoxyglocose (FDG) uptake with positron emission tomography/computed tomography 
(PET/CT) will be performed at baseline and Day 14. Computed tomographic angiography of the abdominal 
aorta and iliac arteries (as part of “Standard of Care”) will be performed at month 12. Duplex ultrasound 
of the aorta will be performed at month 12 while the patients are enrolled in the trial to monitor AAA size. 
Follow up studies are detailed in Table 2, below.  Subjects will return for long-term follow-up visits at six 
month intervals from year 1 (+/- 4 weeks) through year 5 (+/- 4 weeks).  Window ranges for follow-up 
visits are guidelines for scheduling and will not be considered a protocol deviation if visits fall outside of 
these ranges. See Table 3, below, for details on the long-term follow-up visits. 
 
 
• Annual CT abdominal exams beginning at year 1 are considered Standard of Care. 


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Phase I study to examine the safety and efficacy of allogeneic MSCs in suppressing inflammation in patients with small 
abdominal aortic aneurysm (AAA)  
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• MSCs products will be thawed and diluted 1:1 with Plasmalyte. Samples for cell viability (i.e. Trypan 
Blue and/or 7AAD) and 14-day bacterial sterility testing will be obtained. Viability >70% will need to be 
entered in the Certificate of Analysis before the product is released for administration. 
 
• In the event of a positive sterility test result after products infusion, the physician and patient will be 
informed, and the results reported to the IRB and FDA. The positive result will be reported in an 
information amendment submitted to the IND in a timely manner, preferably within 30 calendar days 
after initial receipt of the positive culture test result (21 CFR 312.31). 
 
o Should cultures for detection of bacteria and fungi become positive, the Principal Investigator of 
the study will be notified. The PI will then notify the patient and the appropriate antibiotics will be 
started based on sensitivities of the identified organism.  
 
o A physical examination of will be conducted within 24 hours at which time a complete blood count 
will be obtained. Should there be an elevate white blood cell count (> 11.5K), the patient will be 
admitted to the hospital for intravenous antibiotics or antifungal medications. Should there be no 
clinical evidence of infection the patient will be treated for 7 days with oral antibiotics or anti-fungal 
medication 
 
o A systematic review of potential sources of contamination will be conducted with emphasis on skin 
preparation and draping and the components of the cell transport and preparation system. An 
examination of the sterile packaging for disposable components and the process of sterilization of 
non-disposable components will be performed as part of this review. 
 
o An infection as a result of contamination will be reported as an adverse event within 15 calendar  
 
 
 
 
 
 
 
 
 
 
 
 
Table 2. Follow-Up Schedule 


IRB # 1510579216      PI: Michael P. Murphy, MD 
Phase I study to examine the safety and efficacy of allogeneic MSCs in suppressing inflammation in patients with small 
abdominal aortic aneurysm (AAA)  
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Procedures 
Baseline 
Day 0 
MSC (4-6 
hr. visit)9 
 
Day 
7 F/U 
(+/- 2 
days) 
Day 14 
F/U 
(+/- 5 
days) 
Mo 1 
F/U  
(+/- 
1wk) 
Mo 6 
F/U 
(+/-
2wk) 
Mo 12 
F/U 
(+/-2 
wk) 
Mo 18 
F/U 
(+/-2 
wk) 
Mo 24 
F/U 
(+/-4 
wk) 
Informed 
Consent 
X 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
Physical Exam 
X 
X 
X 
X 
X 
X 
 
 
 
Vital Signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Con. 
Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
AE/SAE 
Evaluations 
X 
X 
X 
X 
X 
X 
X 
X 
X 
QoL 
Questionnaires 
X 
 
 
 
 
X 
X 
X 
X 
Infectious 
Disease Labs1 
X 
 
 
 
 
 
 
 
 
Laboratory 
Evaluations 
X2 
 
 
 
X3 
 
 
 
 
12 Lead ECG 
X8 
 
 
 
X 
 
 
 
 
Duplex 
Ultrasound 
X 
 
 
 
 
X 
X 
X 
X 
Randomization 
X 
 
 
 
 
 
 
 
 
PET CT  
X 
 
 
X 
 
 
 
 
 
CT Angiogram9 
 
 
 
 
 
 
X 
 
X 
Blood Sample4 
 
X5 
X 
X 
X 
X 
X 
X 
X 
Infusion 
Reaction 
Assessment6,7 
 
X 
 
X 
 
 
 
 
 
1. 
Infectious disease testing including basic HIV, Hepatitis C testing.  HLA Typing will be performed at baseline, but is not exclusionary to 
enrollment, nor a protocol deviation if HLA results after study product infusion. 
2. 
Baseline labs ONLY = CBC with differential, Glucose, Sodium, Potassium, Chloride, CO2, BUN, Creatinine, eGFR, hs-CRP, CPK, HbA1C, 
Total Bilirubin, Total Protein, Albumin, Alkaline phosphatase, alanine transaminase (ALT), aspartate transaminase (AST), platelet 
count, PT/INR, Pregnancy (childbearing Females-baseline only). 
3. 
Follow-up labs = CBC with differential, Glucose, Sodium, Potassium, Chloride, CO2, BUN, Creatinine, eGFR, hs-CRP, CPK, Albumin, 
platelet count. 
4. 
Peripheral blood draw for ancillary studies is up to 34 ml. 
5. 
Day of MSC administration blood sample to be collected prior to study product infusion (can be done at physical exam if within 2 
hours of infusion). 


IRB # 1510579216      PI: Michael P. Murphy, MD 
Phase I study to examine the safety and efficacy of allogeneic MSCs in suppressing inflammation in patients with small 
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6. 
Infusion reaction assessment will include:  clinical observation for signs of tachycardia and cutaneous flushing and vital signs (blood 
pressure, heart rate, respiratory rate, and temperature) at 15 min intervals throughout infusion starting 15 min prior to infusion.  
Post infusion vital signs will be monitored at 15 min, 30 min, 1 and 2 hours. 
7. 
Oxygen saturation will be continuously monitored throughout infusion by pulse oximetry starting 15 min prior to infusion through 2 
hours post infusion. 
8. 
Baseline ECG may be obtained any time prior to study product infusion. 
9. 
CT Angiograms beginning at year 1 and performed annually throughout subjects’ participation are considered Standard of Care.  
 
 
Table 3. Long-Term Follow-Up Schedule 
 
Mo 30 
(+/-4wks) 
Mo 36 
(+/-4wks) 
Mo 42 
(+/-4wks) 
Mo 48 
(+/-4wks) 
Mo 54 
(+/-4wks) 
Mo 60 
(+/-4wks) 
Duplex 
Ultrasound1 
X 
X 
X 
X 
X 
X 
CT 
Angiogram3 
 
X 
 
X 
 
X 
QOL 
Questionnaire 
X 
X 
X 
X 
X 
X 
AE/SAE 
Evaluations 
X 
X 
X 
X 
X 
X 
Blood 
Sample2 
X 
X 
X 
X 
X 
X 
1. Duplex ultrasound measured every six months is considered standard of care. 
2. Peripheral blood draw for ancillary studies is 34 ml. 
3. CT Angiograms performed annually are considered Standard of Care. 
 
7.2 Study Data 
Eligible subjects will be invited to participate in the study on a first-come basis. Potential donors must 
provide informed consent to participate. To be eligible for participation, subjects must be between 40 
and 80 years of age with an AAA 30-50 in MTD. 
     7.2.1 Collection of data  
At the discretion of the Investigator and subject to Indiana University School of Medicine requirements, 
data (Table 1) will be collected from each eligible subject providing signed informed consent.  
 
7.3 Procedures for Study Closure 
     7.3.1 Routine study close-out 
The study will end when Indiana University School of Medicine has obtained all data necessary to 
complete its studies of the test product. Study close-out will follow Indiana University School of Medicine 
standard procedures and may include, but is not limited to, review of regulatory documents, collection of 
completed case report forms, reconciliation of study records, removal or destruction of ancillary study 
supplies, and informing the Investigator of remaining obligations (e.g., record retention, final report 
submission to the IRB, financial disclosure updates, etc.).  
      7.3.2 Suspension or premature termination of the study 
 
This study may prematurely terminate at any time because of a regulatory authority decision, a change in 
opinion of the IRB, or at the discretion of the Investigator or Sponsor. If this trial is temporarily suspended 
or prematurely discontinued, Indiana University School of Medicine will promptly notify the 
Investigator(s) and provide instructions. If the study is temporarily suspended, Indiana University School 


IRB # 1510579216      PI: Michael P. Murphy, MD 
Phase I study to examine the safety and efficacy of allogeneic MSCs in suppressing inflammation in patients with small 
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of Medicine will provide guidance on timing and procedures for resuming the study. If the study is 
prematurely discontinued, all study materials must be collected and all study forms completed to the 
extent possible. All such materials must be returned to Indiana University School of Medicine upon 
request.   
 
8. DATA QUALITY ASSURANCE  
The study site will be responsible for the accuracy of data.  Indiana University School of Medicine or its 
agent may periodically conduct monitoring visits to ensure the quality of data collection. 
 
9. STATISTICAL METHODS 
The safety of systemic administration of allogeneic MSCs will be measured by treatment-related adverse 
events. Treatment-related adverse events will be categorized by overlapping systems and severities. The 
three categories of systems are cardiovascular, respiratory, or infectious. Two categories of severity will 
be serious adverse (SAE) and major adverse cardiac events (MACE). For completeness, instances of 
adverse events may appear in more than one category. Within each of these categories adverse events 
will be listed in descending order of frequency for the treatment-group. In addition, for each category, the 
sum and difference between the two routes of delivery of the proportions will be reported as percent 
incidence. Confidence Intervals at the 95% confidence level and P-values for these four groups will be 
calculated. Since four previous trials have not reported adverse events with MSC treatment, confidence 
intervals will be generated by the method of the Wilson Score Interval because they are robust, with good 
coverage probability even for small number of trials and are not degenerate near zero. These intervals 
will be used to summarize the data rather than as any formal inferential statement. No adjustment for 
multiplicity will be made.  
Primary attention in Aim 1 will focus on the detection of cellular immunosuppression activity coincident 
with MSC administration in both proliferation (six decreasing and one increasing) and function (three 
decreasing functional outcomes). Ten mixed model repeated measures with a fixed term for MSC dose 
and their appropriate baseline covariate will be fit. The denominator degrees of freedom will be estimated 
by the method of Kenward and Rodger.12 A compound symmetry covariance structure will be fit if the 
model with the unstructured covariance does not converge. For these data the directionality of superiority 
or inferiority will be assessed. Specifically, the alternative hypotheses are that (1) three T-cell counts 
(CD4+CD28-, CD8+CD28- T-cells and Th-17+ T-cell) will be decreased; (2) CD28- T-cell function will be 
inhibited (decreased; as measured by IFN-γ–producing cells, Perforin-producing cells, and CD57 
expression); (3) T-regulatory cells (CD4+Fox3P+ T-regs) will be increased; and (4) monocytes will be 
decreased (fewer CD45+CD14++CD16-, CD45+CD14+CD16+, CD45+CD14dim/-CD16++). To assess the 
individual hypotheses, the model-derived, confidence interval for the intercept will be reported. 
Confidence intervals at the 95% level from the same models will be constructed to estimate the difference, 
or contrast, between routes of administration 
 
9.1 Bias Minimization 
All subjects meeting the specified eligibility criteria will be enrolled on a first-come basis.  
9.2 Planned Analyses 
The clinical study report will contain only summary data analyses reflecting safety profiles, and summary 
data analyses of efficacy.  All patient data will remain coded during analyses to maintain patient 
confidentiality. 
 


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Phase I study to examine the safety and efficacy of allogeneic MSCs in suppressing inflammation in patients with small 
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10. ADVERSE EVENT REPORTING 
10.1 Adverse Events and Stopping Rules 
Adverse events occurring during the enrollment period should be documented by the Investigator in 
progress notes, but will not be collected or analyzed by Indiana University School of Medicine unless 
considered serious by the Investigator. Adverse events will be reported according to federal guidelines for 
safety reporting for Investigational New Drug Application (IND). 
 
Serious adverse events (SAEs) encountered during study enrollment will be documented by the 
Investigator and reported to Indiana University School of Medicine immediately upon discovery. SAEs are 
defined under current Good Clinical Practice (cGCP) guidelines as events that result in one or more of the 
following: 
• 
life-threatening illness or injury;  
• 
permanent impairment of a body structure or a body function;  
• 
medically necessary in-patient hospitalization;  
• 
medical or surgical intervention necessary to prevent permanent impairment to body 
structure or function; or  
• 
fetal distress, fetal death, or congenital abnormality. 
 
Serious events that affect the rights, safety, or welfare of subjects must be documented on a form and 
be reported immediately to Indiana University School of Medicine and to the Investigator’s IRB 
according to that IRB’s policies. 
 
Major Adverse Cardiac Events (MACE). MACE endpoints will include: death, nonfatal myocardial 
infarction, including, Q-wave, non Q-wave, and CK/CKMB elevation, stroke, transient ischemic attack 
(TIA), hospitalization for heart failure, hospitalization for hypo or hypertension, life-threatening 
arrhythmia, and aneurysm rupture, which will be collected throughout the 6-month time period.   
 
Severity Assessment. We will use the Common Terminology Criteria for Adverse Events (CTCAE), version 
4.0, for detailed descriptions of Severity Grades.  The CTCAE schema is classified by body system and 
event using the MedDRA hierarchy and provides descriptions of events that qualify under each severity 
rating.  
                The following table contains general descriptions of Adverse Event Severity Grades. 
 
Severity Grade 
Description 
1 
Mild. Asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention is not indicated.  
2 
Moderate. Minimal, local, or non-invasive intervention indicated or limiting 
activities of daily living (i.e. preparing meals, shopping for groceries/clothes, 
managing money, using telephone, etc.) 
3 
Severe or medically significant but not immediately life-threatening. 
Hospitalization or prolongation of hospitalization indicated OR disabling OR 
limiting self-care (e.g. bathing, dressing, feeding self, using toilet, taking 
medications, etc.) 
4 
Life-threatening consequences; urgent intervention indicated. 


IRB # 1510579216      PI: Michael P. Murphy, MD 
Phase I study to examine the safety and efficacy of allogeneic MSCs in suppressing inflammation in patients with small 
abdominal aortic aneurysm (AAA)  
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5 
Death. Death related to adverse event. 
 
 
3. Stopping Rules 
With any of the events listed below, the trial will be stopped, no additional patients will be enrolled and 
the FDA, the NIH, DMSB, and IRB will be notified. A comprehensive review of the cases will be 
conducted by the principal investigator, study coordinator, DMSB, and selected specialists to determine 
the etiology of each event. A decision to permanently halt or resume the study will be rendered by the 
aforementioned boards independent of the principal investigator. 
• 
Expansion of AAA by > 7 mm. MTD in five or more patients in the MSC treatment group in a 6-
month period. 
• 
Two or more aortic aneurysm ruptures in the MSC treatment group within a 12-month period. 
• 
One non-pulmonary embolism within a 12-month period indicative of acute respiratory distress 
syndrome (ARDS). 
• 
One death related to MSC infusion. 
 
10.2 Sponsor Contact for Serious Adverse Event Reporting 
 
 
 
11. RISK ANALYSIS 
11.1 Potential Risks of the Investigational Product and Clinical Investigation 
Study sites will not be provided with an investigational device. 
 
The types of risk associated with injection of allogeneic MSCs align with those associated with injection of 
autologous bone marrow mononuclear cells (ABMNCs), most notably rash, mild fever, and myalgia. These 
risks are mild and rare. These risks are all stated in the consent form.  
 
11.2 Potential Benefits of the Investigational Product and Clinical Investigation 
Subjects are not expected to benefit in any way from their participation in the study. 
The studies made possible by the data collected in this study are expected to lead to effective 
therapeutic strategies using MSCs or their secreted products to suppress expansion of small AAA 
negating the need for surgery and preventing rupture. 
 
11.3 Minimization of Risks 
Although the risk to subjects participating in the study is anticipated to be minimal, the clinician, at 
his/her discretion, will not collect data from those individuals for whom collection is judged to pose an 
unusually high risk of physical or mental harm or discomfort. Participation in this study poses no risk to 
study personnel other than that normally encountered during standard practice. These risks will be 
minimized by adherence to the following guidelines: 
Michael P. Murphy, MD 
1801 N. Senate Blvd. 
MPC2, #3500 
Indianapolis, IN 46202 


IRB # 1510579216      PI: Michael P. Murphy, MD 
Phase I study to examine the safety and efficacy of allogeneic MSCs in suppressing inflammation in patients with small 
abdominal aortic aneurysm (AAA)  
Page 26 
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Indiana University School of Medicine 
  
• 
Personnel should wear appropriate personal protective equipment to avoid contact of the eyes 
or skin with hazardous materials or products derived from biological sources.  
 
12. INVESTIGATOR RESPONSIBILITIES 
12.1 Site Qualification and Study Oversight 
The PI is responsible for general administration of the study.  
Before the study, the PI must: 
• 
Obtain approval to conduct the study from the study site’s IRB; 
• 
Sign the Signature Page him/herself and have all sub-investigators sign the  Signature Page and 
return it to Indiana University School of Medicine; 
• 
Provide financial disclosures to Indiana University School of Medicine for themselves and all sub-
investigators participating in study conduct, per Title 21CFR 54 (see Section 12.4 below).  
 
 
During the study, the PI must ensure that:  
• 
The study is conducted ethically;  
• 
Case report forms (CRFs), including Subject ICFs, are provided with each transfer of data 
requiring informed consent; and 
• 
All other study forms are completed as instructed by Indiana University School of Medicine. 
 
In the case of completion or termination of the study or an Investigator's role in the study, or at Indiana 
University School of Medicine request, all study materials must be returned to Indiana University School 
of Medicine. 
 
12.2 Case Report Forms/Electronic Data Records 
As used in this protocol, the term CRF should be understood to refer to either a paper form or an electronic 
data record or both, depending on the data collection method(s) used. 
Original CRFs are the sole property of Indiana University School of Medicine and should not be made 
available in any form to third parties, except for authorized representatives of Indiana University School 
of Medicine or appropriate regulatory authorities, without written permission from Indiana University 
School of Medicine.  
 
It is the PI's responsibility to ensure completion, review, and approval of all CRFs. CRFs must be signed by 
the PI or by an authorized staff member. These signatures serve to attest that the information contained 
on the CRFs is true. At all times, the PI has final personal responsibility for the accuracy and authenticity 
of all clinical and laboratory data entered on the CRFs.  
 
12.3 Access to Source Documents 
Indiana University School of Medicine or its agents and appropriate regulatory authorities shall be granted 
direct access to all study-related documents to perform verification that the protocol and all applicable 
current Good Laboratory Practices (cGLPs), Good Clinical Practices (GCPs), and regulations are being 
followed and to confirm that study documents are complete and accurate. It is important that 
Investigator(s) and their relevant personnel be made available during monitoring visits and any audits or 
inspections, and that sufficient time is allotted for the process.  
 


IRB # 1510579216      PI: Michael P. Murphy, MD 
Phase I study to examine the safety and efficacy of allogeneic MSCs in suppressing inflammation in patients with small 
abdominal aortic aneurysm (AAA)  
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Indiana University School of Medicine 
  
12.4 Financial Disclosure 
Investigators must provide Indiana University School of Medicine with sufficient, accurate financial 
information in accordance with local regulations to allow Indiana University School of Medicine to submit 
complete and accurate financial certification or disclosure statements to the appropriate health 
authorities. Investigators are responsible for providing information to Indiana University School of 
Medicine concerning their relevant financial interests during the course of the study and for 1 year after 
completion of the study. Conflicts of interest should be disclosed as required by law.  
 
Financial support for this project is provided by Indiana Clinical and Translational Sciences Institute 
(CTSI).   
 
12.5 Deviations from the Study Protocol 
An Investigator may not deviate from the study protocol without prior approval by Indiana University 
School of Medicine unless the deviations are necessary under emergency circumstances to protect the 
rights, safety, or well-being of human subjects or the scientific integrity of the clinical investigation. These 
deviations must be documented and promptly reported to Indiana University School of Medicine and, if 
applicable, to the IRB providing oversight of the study. Protocol deviations may result in corrective and 
preventive actions and/or disqualification of the Investigator.  
 
12.6 Record Retention 
To enable evaluations and/or audits from regulatory authorities or Indiana University School of Medicine, 
the PI and all sub-investigators agrees to retain all study records, including copies of all CRFs, UADE forms, 
and source documents, for 3 years following completion of the project dependent upon the study data. 
The Investigator must obtain the Indiana University School of Medicine written permission before 
disposing of any records, even if retention requirements have been met. 
If an Investigator relocates, retires, or for any other reason withdraws from the trial, Indiana University 
School of Medicine must be notified in advance, and study records must be transferred to a designee 
acceptable to Indiana University School of Medicine. This designee might be another Investigator, another 
institution, or Indiana University School of Medicine itself. 
 
12.7 Publication Policy 
The results of this study will be submitted for publication to a medical journal.  The PI agrees that any 
publication of data from this study will comply with Indiana University School of Medicine publication 
policy, the instructions to authors outlined by the editor of the journal or conference proceedings where 
the data is to be published, and the spirit of recommendations made in the good publication practice 
guidelines (GPP2) of the International Society of Medical Publication Professionals. Indiana University 
School of Medicine has the right to review any manuscripts, presentations, or abstracts that originate 
from this study or that utilize these data before they are submitted for publication or other means of 
communication.  
 
13. ETHICS AND COMPLIANCE 
13.1 Informed Consent and De-Identification  
     13.1.1 Prospectively collected data 
All subjects will be given a copy of the IRB-approved ICF to review before their study participation begins. 
The Investigator will explain all aspects of the study in lay language and answer all of the potential 
participant’s questions regarding the study. If the participant decides to participate in the study, s/he will 


IRB # 1510579216      PI: Michael P. Murphy, MD 
Phase I study to examine the safety and efficacy of allogeneic MSCs in suppressing inflammation in patients with small 
abdominal aortic aneurysm (AAA)  
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Indiana University School of Medicine 
  
be asked to sign and date the ICF. Subjects who refuse to participate or who withdraw from the study will 
be treated without prejudice. 
 
13.2 IRB Review 
The PI is required to obtain IRB oversight of the research study. The IRB must be provided with the Indiana 
University School of Medicine-approved study protocol. Performance of the study may not begin until 
written evidence of IRB approval has been provided to Indiana University School of Medicine.  
The conduct and performance of this study will be in accordance with applicable Sponsor and Investigator 
responsibilities as described in Title 21 CFR 812 and other Good Clinical Practice guidance.  
IRB/Ethics Committee oversight will be required as human subjects or data from humans are being used. 
This protocol and the associated informed consent document(s) (if applicable) must be submitted to the 
IRB for review and approval. Performance of the study at a given site may not begin until written evidence 
of IRB oversight has been provided to an Indiana University School of Medicine study manager. IRB Review 
and approval must comply with Title 21 CFR 812 Subpart D. 
 
13.3 Confidentiality of Data and Patient Records 
The study institution shall keep all records associated with this study for at least 3 years, as specified in. 
Investigators will keep all records associated with this study for at least 3 years. 
 
13.3.1 Provisions to Protect the Privacy Interests of Participants 
The PI and/or study institution shall provide sufficient information to allow the IRB to evaluate the 
researcher’s provisions to maintain the confidentiality of data. 
 
Privacy data will be maintained in accordance with HIPAA and other applicable policies and local law.  
 
All records will be kept in a locked file in the PI’s office. All patient records and labels will be deidentified 
with regards to the patient’s name, medical record number, address, phone number, social security 
number, and date of birth. 
 
14. REFERENCES 
1. Nordon IM, Hinchliffe RJ, Loftus IM, Thompson MM. Pathophysiology and epidemiology of 
abdominal aortic aneurysms. Nat Rev Cardiol. 2011; 8(2):92-102. 
2. Stroupe KT, Lederle FA, Matsumara, JS, et a. Cost effectiveness or open versus endovascular 
repair of abdominal aortic aneurysm in the OVER trial. J Vasc Surgery 2012; 56:901-909. 
3. Meijer CA, Stijnen T, Wasser M, et al. Doxycycline for Stabilization of Abdominal Aortic 
Aneurysms: A Randomized Trial. Ann Intern Med. 2013;159:815-823. 
4. Di Nicola M, Carlo-Stella C, Magni M, et al. Human bone marrow stromal cells suppress T-
lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 2002; 
99:3838-3843. 
5. Nauta AJ, Fibbe WE. Immunomodulatory properties of human mesenchymal stromal cells. Blood 
2007;110:3499-3506. 
6. Sharma AK, Lu G, Jester A, Johnston W, Zhao Y, Hajzus V, Saadatzadeh MR, Su G, Bhamidipati 
CM, Mehta G, Kron IL, Laubach VE, Murphy MP, Ailawadi G and Upchurch GR. Experimental 
abdominal aortic aneurysm formation is mediated by IL-17 and attenuated by mesenchymal 
stem cell treatment. Circulation 2012;126:S38-S45. 


IRB # 1510579216      PI: Michael P. Murphy, MD 
Phase I study to examine the safety and efficacy of allogeneic MSCs in suppressing inflammation in patients with small 
abdominal aortic aneurysm (AAA)  
Page 29 
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Indiana University School of Medicine 
  
7. Hare JM, Traverse JH, Henry TD, Dib N, Strumpf RK, Schulman SP, Gerstenblith G, DeMaria AN, 
Denktas AE, Gammon RS, Hermiller JB, Jr., Reisman MA, Schaer GL, Sherman W. A randomized, 
doubleblind, placebo-controlled, dose-escalation study of intravenous adult human 
mesenchymal stem cells (prochymal) after acute myocardial infarction. J Am Coll Cardiol. 
2009;54(24):2277-86. 
8. Hare JM, Fishman JE, Gerstenblith G, et al. Comparison of allogeneic vs. autologous bone 
marrow derived mesenchymal stem cells delivered by transendocardial injection in patients with 
ischemic cardiomyopathy. JAMA. 2012;308 (22):2369-2379. 
9. Weiss DL, Casaburi R, Flannery R, et al. A Placebo-Controlled Randomized Trial of Mesenchymal 
Stem Cells in Chronic Obstructive Pulmonary Disease. Chest. 2013;143:1590-1598.  
10. Le Blanc K, Frassoni F, Ball L, et al; Developmental Committee of the European Group for Blood 
and Marrow Transplantation. Mesenchymal stem cells for treatment of steroid-resistant, severe, 
acute graft versus host disease: a phase II study. Lancet. 2008; 371(9624):1579-1586. 
11. Tan J,Wu W, Xu X, et al. Induction Therapy With Autologous Mesenchymal Stem Cells in Living-
Related Kidney Transplants. JAMA. 2012; 307:1169-1177. 
12. Kenward, MG,Roger, J H Small Sample Inference for Fixed Effects from Restricted Maximum 
Likelihood. Biometrics, 1997;53: 983–997. 
 
 
<< End of Document >> 
 
 

ICF_001.pdf: 
Official Title:  Phase I study to examine the safety and efficacy of allogeneic MSCs in suppressing 
inflammation in patients with small abdominal aortic aneurysm (AAA)
ClinicalTrials.gov Identifier: NCT02846883
Date of Document:  July 15, 2021 


         A Phase I study to examine the safety and efficacy of allogeneic Mesenchymal Stromal Cells in suppressing              
         inflammation in patients with small abdominal aortic aneurysm (AAA); IRB#1510579216 
 
 
Physical exams 
and medical 
history collection 
 
 
 
 
 
Blood draws to 
test your blood 
 
 
 
Electrocardiogram 
(ECG) to check 
your heart 
function 
 
 
 
 
 
PET / CT scans to 
check the size and 
shape of your 
aneurysm 
 
 
 
 
 
Ultrasound to 
monitor the size 
of your aorta 
 
 
Cell Infusion 
Procedure 
 
BENEFITS OF PARTICIPATING IN THIS RESEARCH:  A possible benefit of your participation in this study is the 
slowing of your aneurysm’s growth; however, you may not benefit at all.   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Accessing your medical 
records has the risk of a 
potential loss of 
confidentiality. 
 
Blood Draws have the risk of 
discomfort, bruising, 
infection, excess bleeding, 
clotting and fainting. 
 
ECG has the risk of slight 
discomfort from the adhesive 
patches. 
 
PET / CT scans has the risk of 
radiation exposure; risk of an 
allergic reaction from the dye 
injection and the dye can 
also cause injury to the 
kidneys. 
 
There are no known risks to 
ultrasounds. 
Cell Infusion Procedure has 
the risk of fever, rash, rapid 
(fast) heart rate, or shortness 
of breath. 
 
RISKS 
PROCEDURES 
WHERE & HOW LONG 
Procedures for 
veterans will take 
place at Roudebush 
VAMC and for non-
veterans at IU Health 
Methodist Hospital.   
 
Your overall 
participation will last 
five years. 
If you have questions, 
please contact Dr. 
Michael Murphy at 317-
988-4049. 
Please review the Informed Consent Statement for details about these topics and additional things you should know before 
making a decision about whether to participate in this study.   
What We are Researching:  This research project is hoping to find out if taking a special kind of cells from a 
healthy human being and injecting them into people with an abdominal aortic aneurysm will decrease 
inflammation and slow down the enlargement of their aneurysm. 
 
Why You:  You have an abdominal aortic aneurysm discovered on the scan requested by your doctor. 
 
Do You Have to Participate:  No, participation is voluntary. You may choose to take part in this research or 
even leave the study at any time after you choose to take part.  Your choice will not change the benefits to 
which you are entitled and will not affect your relationship with Roudebush VAMC or IU Health. 
If you choose to participate in this research project, this is what we will ask you to do and what that means for you: 
There is no payment for 
your participation, but 
you will receive meal 
vouchers and your travel 
may be covered. 


Department of Veterans Affairs 
VA Research 
Consent Form 
Subject Name:  
Date:   
Title of Study:  
A Phase I study to examine the safety and efficacy of allogeneic Mesenchymal Stromal 
Cells in suppressing inflammation in patients with small abdominal aortic aneurysm 
(AAA); IRB #1510579216 
Sponsor: 
VAMC  
Principal Investigator: 
Michael P. Murphy, MD 
VAMC:  Roudebush VA   
 
   Indianapolis 
 
VERSION CONTROL 
Version Date   
 
Page 2 of 14 
 
Created/Updated: 
           7/15/21 
 
 
Master Template for: Roudebush  
VA Form 10-1086 
 
07/2015 
 
 
 
                                                                                                                                                                                                                                                                                                                                                          O 
You are invited to participate in a research study to determine the safety and explore the effectiveness of 
allogeneic (not your cells but those of another human) mesenchymal stromal cells (MSCs) in decreasing 
inflammation and possible enlargement of your abdominal aortic aneurysm.  You were selected as a possible 
subject because you have an abdominal aortic aneurysm discovered on the ultrasound or computed tomographic 
(“CT”) scan requested by your doctor.  We ask that you read this form and ask any questions you may have 
before agreeing to be in the study.  
 
Michael P. Murphy, MD, Indiana University, Department of Surgery, and Richard Roudebush VAMC and IU 
Health Methodist Hospital are conducting the study. 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 
your aneurysm. We will also be collecting blood samples to study special inflammatory cells that cause 
aneurysms as well as asking you to have an abdominal “PET” (positron emission tomography) scan that can 
measure inflammation directly in your aneurysm. Dr. Murphy has no financial relationship with the design, 
conduct or outcome of this study. Dr. Murphy is acting as the Principal Investigator for this study and will not 
receive salary support for his time commitment to the study.  
 
If you currently have malignant cancer of any kind or if you have had malignant cancer within the last 5 years 
that has been untreated, except basal cell skin carcinoma, you cannot take part in this study.   
 
Purpose of study and how long it will last:  
 
The purpose of this study is to determine the safety and explore the effectiveness of MSCs given through a vein 
in your arm into your circulation.  The study doctor is researching this method for decreasing the activity of certain 
inflammatory cells called T cells and B cells and increasing the activity of anti-inflammatory “Regulatory” cells to 
see if this procedure can help decrease inflammation and enlargement of your aneurysm. Our research has 
shown MSCs can prevent aneurysm enlargement in mouse models. This will be the first study to see if MSCs 
can do the same in humans.  The allogeneic MSCs will be donated by a healthy volunteer from Case Western 
Reserve University in Cleveland, Ohio.  The Case Comprehensive Cancer Center (CCCC) at Case Western 
Reserve University is located at WRB 6-303 2103 Cornell Road Cleveland, Ohio 44106.  The MSCs will be 
delivered to the IU Health University Hospital Cell Therapy Lab in Indianapolis, IN.  The frozen sample of MSCs 
will be thawed and delivered to the SICU at the Roudebush VA Hospital, where your infusion of these cells will 
take place.   
 
Description of the study including procedures to be used:  
If you agree to participate, you will be one of up to 50 people who will participate in this study. 


Department of Veterans Affairs 
VA Research 
Consent Form 
Subject Name:  
Date:   
Title of Study:  
A Phase I study to examine the safety and efficacy of allogeneic Mesenchymal Stromal 
Cells in suppressing inflammation in patients with small abdominal aortic aneurysm 
(AAA); IRB #1510579216 
Sponsor: 
VAMC  
Principal Investigator: 
Michael P. Murphy, MD 
VAMC:  Roudebush VA   
 
   Indianapolis 
 
VERSION CONTROL 
Version Date   
 
Page 3 of 14 
 
Created/Updated: 
           7/15/21 
 
 
Master Template for: Roudebush  
VA Form 10-1086 
 
07/2015 
 
 
 
                                                                                                                                                                                                                                                                                                                                                          O 
 
If you agree to be in the study, you must sign this consent form prior to undergoing any study related procedures.  
If you agree to participate in the study, the following things will happen: 
 
You will be randomized into one of three different time treatment groups based on MSC dose or placebo. Group 
1 will receive 1 million MSCs per kilogram of your body weight intravenously, Group 2 will receive 3 million 
MSCs per kilogram of your body weight intravenously, and Group 3 will receive the placebo (control) which is 
the solution the MSCs are stored in, called Plasmalyte A. Randomization means that you are placed in a group 
by chance (like flipping a coin).  You will not have a choice into which group you are placed, but you have a 
66% chance that you will be in one of the MSC treatment groups.  At your Month 24 follow-up visit, you will 
have the option to be unblinded from your study treatment group.   
 
The following evaluations will be carried out at the baseline screening visit to determine if you are eligible for 
the study.  A study calendar is also included later in this consent which shows the study procedures and the 
timing of those procedures.  
 
Baseline screening includes: 
• 
Complete medical history and physical exam. Your medical history includes: your current medications 
and medications you have taken in the past 30 days; all medical problems that you have now or used to 
have; all surgeries and procedures that you have had; and information about you such as age, gender, 
race, height/weight. 
• 
Vital signs (such as blood pressure, heart rate, respiratory rate, temperature) 
• 
Pregnancy test for women of childbearing age;  
• 
Blood tests (complete blood count, serum chemistry, liver panel, lipid panel, infectious disease testing, 
hs-CRP, CPK, HLA typing) will be obtained to make sure you do not have current infection, and to 
make sure your kidneys and other organs are functioning normally.   
• 
Electrocardiogram (ECG) to check your heart function;  
• 
18-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (PET/CT) scan to 
measure the inflammation of your aneurysm at baseline and Day 14 to monitor the size of your 
aneurysm.  You will have CT Angiograms annually from Month 12 through the end of your participation 
at Month 60.  Annual CT Angiograms are considered standard of care. 
• 
Duplex ultrasound of your aorta at baseline and every 6 months while you are enrolled in this study to 
monitor the size of your aneurysm. 
• 
Current medication list. 


Department of Veterans Affairs 
VA Research 
Consent Form 
Subject Name:  
Date:   
Title of Study:  
A Phase I study to examine the safety and efficacy of allogeneic Mesenchymal Stromal 
Cells in suppressing inflammation in patients with small abdominal aortic aneurysm 
(AAA); IRB #1510579216 
Sponsor: 
VAMC  
Principal Investigator: 
Michael P. Murphy, MD 
VAMC:  Roudebush VA   
 
   Indianapolis 
 
VERSION CONTROL 
Version Date   
 
Page 4 of 14 
 
Created/Updated: 
           7/15/21 
 
 
Master Template for: Roudebush  
VA Form 10-1086 
 
07/2015 
 
 
 
                                                                                                                                                                                                                                                                                                                                                          O 
• 
If you are on a blood thinner medication, a pre-operative blood test to check your blood clotting ability 
will be performed.  This will require approximately one teaspoon of blood drawn from a vein in your 
arm. 
 
The baseline procedures may take most of the day (approximately 4 to 5 hours) and will take place at the 
Roudebush VA Hospital if you are a veteran or IU Health Methodist Hospital if you are not a veteran. 
 
Veterans will be admitted to Richard L. Roudebush VA Hospital for the infusion of the mesenchymal stromal 
cells and stay in the SICU for up to 2-4 hours, until the assessments have been completed.  The study doctor 
will assess you before you are discharged home. If you are a veteran, all study visits will occur at the Richard 
L. Roudebush VA Hospital, Indianapolis, Indiana. 
 
If you are not a veteran, the infusion procedure will take place at the Clinical Research Center at IU Health 
University Hospital, 5050 University Blvd., Indianapolis, IN. This will be the only study visit that will occur at 
University Hospital; all other study related visits and procedures will take place at IU Health Methodist Hospital. 
 
Mesenchymal Stromal Cell Infusion Procedure: 
Depending upon the group to which you are assigned, we will infuse allogeneic (cells that are not your own) 
mesenchymal stromal cells (MSCs), or a solution of Plasmalyte A (placebo) intravenously into a vein in your 
arm. MSCs will circulate through your bloodstream where they will release signals that turn off inflammation and 
injury. This infusion procedure will be performed over 30-45 minutes while we monitor your heart rate and rhythm, 
blood pressure, and breathing, including oxygen levels (pulse oximetry). This monitoring will require attachment 
of pads to your chest, a blood pressure cuff on your arm, and a pulse oximeter on your fingertip. Before the 
infusion procedure, up to 34 milliliters of blood, about 2.5 tablespoons will be drawn from a vein for laboratory 
analysis.  Blood will be drawn up to 12 times (approx. 2 cups total over a duration of 5 years) throughout the 
course of your participation in the study.  After the infusion is complete, you will be monitored for an additional 
two hours, then discharged home. 
 
A portion of the blood sample collected at each time point will be sent to a laboratory directed by Dr. Phillip Yang, 
MD, Professor of Medicine, Division of Cardiology.  This lab is located at 300 Pasteur Drive, a260 Palo Alto, 
California, 94304.  Your samples will not be identifiable which means that researchers will not have any personal 
identifiable information to link your sample to your health records, nor will they know to which you will be 
randomized.  After laboratory analysis, your sample will be discarded and no portion will be stored or banked for 
future use in research. 
 
We will follow your health for 5 years to see if you have developed any problems after MSC administration and 
to see if we can determine if MSCs have had any effect in decreasing inflammatory cell numbers in your 


Department of Veterans Affairs 
VA Research 
Consent Form 
Subject Name:  
Date:   
Title of Study:  
A Phase I study to examine the safety and efficacy of allogeneic Mesenchymal Stromal 
Cells in suppressing inflammation in patients with small abdominal aortic aneurysm 
(AAA); IRB #1510579216 
Sponsor: 
VAMC  
Principal Investigator: 
Michael P. Murphy, MD 
VAMC:  Roudebush VA   
 
   Indianapolis 
 
VERSION CONTROL 
Version Date   
 
Page 5 of 14 
 
Created/Updated: 
           7/15/21 
 
 
Master Template for: Roudebush  
VA Form 10-1086 
 
07/2015 
 
 
 
                                                                                                                                                                                                                                                                                                                                                          O 
circulation as well as decreasing inflammation in your aneurysm.  After your 5-year follow-up visit, you will have 
completed participation in the study; however, because of the possibility that your aneurysm may enlarge you 
need to follow-up with your private physician after your participation in the study ends. 
 
It is important for you to follow the directions for treatment and the study.  The study requires you to return to 
the study doctor for follow-up evaluations of your progress at days 7, 14 and months 1, 6, 12, 18, and 24. You 
will also return to the VAMC in Indianapolis at 6-month intervals through your 5-year visit.  Screening and 
follow-up visits will take place at the Peripheral Vascular Clinic located on the first floor of the Richard 
Roudebush Veterans Administration Center, 1481 West 10th Street, Indianapolis, IN  46202.  
 
For Non-Veterans, screening and follow up evaluations will take place in the Vascular Clinic at IU Health 
Methodist Hospital, 1801 N. Senate Blvd., Indianapolis, IN 46202.  Evaluation of your progress at days 7, 14 
and months 1, 6, 12, 18, and 24 will be completed at IU Health Methodist Hospital. You will also return at 6-
month intervals through your 5-year visit. 
 
Calendars have been inserted below so that you can see the number of study visits you will have and the time 
intervals. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Department of Veterans Affairs 
VA Research 
Consent Form 
Subject Name:  
Date:   
Title of Study:  
A Phase I study to examine the safety and efficacy of allogeneic Mesenchymal Stromal 
Cells in suppressing inflammation in patients with small abdominal aortic aneurysm 
(AAA); IRB #1510579216 
Sponsor: 
VAMC  
Principal Investigator: 
Michael P. Murphy, MD 
VAMC:  Roudebush VA   
 
   Indianapolis 
 
VERSION CONTROL 
Version Date   
 
Page 6 of 14 
 
Created/Updated: 
           7/15/21 
 
 
Master Template for: Roudebush  
VA Form 10-1086 
 
07/2015 
 
 
 
                                                                                                                                                                                                                                                                                                                                                          O 
 
Follow-Up Schedule 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
     
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Procedures 
 
 
Baseline 
Day 0 
MSC 
 (2-4 
hr) 
Day 7 
F/U 
(+/-2 
days) 
Day 14 
F/U      
(+/- 5 
days) 
Mo 1 
F/U 
(+/- 
1wk) 
 
Mo 6 
F/U 
(+/-
2wk) 
Mo 12 
F/U 
(+/-
2wk) 
Mo 18 
F/U 
(+/- 
2wk) 
Mo 24 
F/U 
(+/-4wk) 
Informed 
Consent 
X 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
Physical Exam 
X 
X 
X 
X 
X 
X 
 
 
 
Vital Signs 
X 
X 
X 
X 
X 
X 
X 
X 
     X 
Con. 
Medications 
X 
X 
X 
X 
X 
X 
X 
X 
     X 
AE/SAE 
Evaluations 
X 
X 
X 
X 
X 
X 
X 
X 
     X 
QoL 
Questionnaires 
X 
 
 
 
 
X 
X 
X 
     X 
Infectious 
Disease Labs 
X 
 
 
 
 
 
 
 
 
Laboratory 
Evaluations 
X 
 
 
 
X 
 
 
 
 
12 Lead ECG 
X 
 
 
 
X 
 
 
 
 
Duplex U/S 
X 
 
 
 
 
X 
X 
X 
     X 
Randomization 
X 
 
 
 
 
 
 
 
 
    PET/CT  
X 
 
 
X 
 
 
 
 
 
CT Angiogram 
 
 
 
 
 
 
X 
 
X 
Blood Sample 
 
X 
X 
X 
X 
X 
X 
X 
     X 
Infusion 
Reaction 
Assessment 
 
X 
 
X 
 
 
 
 
 


Department of Veterans Affairs 
VA Research 
Consent Form 
Subject Name:  
Date:   
Title of Study:  
A Phase I study to examine the safety and efficacy of allogeneic Mesenchymal Stromal 
Cells in suppressing inflammation in patients with small abdominal aortic aneurysm 
(AAA); IRB #1510579216 
Sponsor: 
VAMC  
Principal Investigator: 
Michael P. Murphy, MD 
VAMC:  Roudebush VA   
 
   Indianapolis 
 
VERSION CONTROL 
Version Date   
 
Page 7 of 14 
 
Created/Updated: 
           7/15/21 
 
 
Master Template for: Roudebush  
VA Form 10-1086 
 
07/2015 
 
 
 
                                                                                                                                                                                                                                                                                                                                                          O 
 
Long-Term Follow-Up Schedule 
 
 
 
Mo 30 
(+/-4wks) 
Mo 36 
(+/-4wks) 
Mo 42 
(+/-4wks) 
Mo 48 
(+/-4wks) 
Mo 54 
(+/-4wks) 
Mo 60 
(+/-4wks) 
Duplex 
Ultrasound 
X 
X 
X 
X 
X 
X 
CT Angiogram 
 
X 
 
X 
 
X 
QOL 
Questionnaire 
X 
X 
X 
X 
X 
X 
AE/SAE 
Evaluations 
X 
X 
X 
X 
X 
X 
Blood Sample 
X 
X 
X 
X 
X 
X 
 
Risks:  
While on the study, the risks are: 
 
Cell Infusion  
Risks associated with MSC infusion are fever, rash, rapid heart rate, or shortness of breath. These risks are rare 
and you will be given medication (Benadryl) to prevent these risks. Your heart rate and rhythm as well as 
breathing and blood oxygen level will be monitored during and after the MSC infusion process to recognize these 
rare risks. 
 
Blood Draws  


Department of Veterans Affairs 
VA Research 
Consent Form 
Subject Name:  
Date:   
Title of Study:  
A Phase I study to examine the safety and efficacy of allogeneic Mesenchymal Stromal 
Cells in suppressing inflammation in patients with small abdominal aortic aneurysm 
(AAA); IRB #1510579216 
Sponsor: 
VAMC  
Principal Investigator: 
Michael P. Murphy, MD 
VAMC:  Roudebush VA   
 
   Indianapolis 
 
VERSION CONTROL 
Version Date   
 
Page 8 of 14 
 
Created/Updated: 
           7/15/21 
 
 
Master Template for: Roudebush  
VA Form 10-1086 
 
07/2015 
 
 
 
                                                                                                                                                                                                                                                                                                                                                          O 
Risks associated with drawing blood from your arm include minimal discomfort and/or bruising. Infection, 
excess bleeding, clotting, and fainting are also possible, although unlikely. In order to minimize these risks, 
blood will be drawn by experienced technicians.  
 
ECG 
You may experience slight discomfort when the adhesive patches are removed. Care will be taken when 
removing the adhesive patches to reduce your discomfort.  
 
18F-fluorodeoxyglucose (FDG) uptake with positron emission tomography/computed tomography 
(PET/CT).  
 
18-FDG PET/CT is performed two times during this study.  Each test involves exposure to radiation.  Your 
participation in this research study involves exposure to radiation in addition to what you may receive as part of 
your standard care. The benefit from the radiation you receive for your standard care typically outweighs the 
risk because it allows your doctor to provide appropriate medical care; however, the additional radiation “dose” 
you receive for research purposes may not benefit you personally. Regulatory agencies have established 
annual radiation dose limits for both individuals who work with radiation (e.g. x-ray technologists, radiologists, 
etc.) and those participating in research studies. If you decide to participate in this research study, the radiation 
dose you receive will be below the annual limit for radiation workers. 
 
Radiation has been shown to cause cancer and/or leukemia from doses that are significantly higher than the 
additional annual radiation dose you will receive by participating in this study. According to the Health Physics 
Society (an international organization that specializes in radiation protection), the increased risk of health 
effects (i.e. cancer and/or leukemia) from radiation doses of this amount is either too small to be observed or 
nonexistent in a normal population. While there is no evidence that any risk exists for humans exposed to such 
low levels, it is assumed that the risks rise with lifetime accumulated dose from all sources of ionizing radiation, 
including the doses you receive from medical procedures and the environment. You should also be aware that 
everyone’s sensitivity to radiation is not the same and some diseases (e.g. genetic diseases, diseases 
affecting DNA repair, and immune diseases such as HIV) may make you more sensitive to the effects and 
consequences of the radiation exposure than the normal population. Finally, you should know that even if there 
is an increased risk of an effect, it could be 5 to 20 years before any effect would actually occur. Thus, you may 
want to factor in your age, overall health, and the number of medical radiation procedures that you’ve had 
when determining if this risk is acceptable to you. The calculated effective dose resulting from your 
participation in this study is available upon request. 
There is a risk of an allergic reaction, which may be serious, whenever contrast material containing iodine is 
injected. A patient with a history of allergy to x-ray dye may be advised to take hydrocortisone and Benadryl for 
24 hours before 18-FDG PET/CT to lessen the risk of allergic reaction or advised to not participate in the study. 


Department of Veterans Affairs 
VA Research 
Consent Form 
Subject Name:  
Date:   
Title of Study:  
A Phase I study to examine the safety and efficacy of allogeneic Mesenchymal Stromal 
Cells in suppressing inflammation in patients with small abdominal aortic aneurysm 
(AAA); IRB #1510579216 
Sponsor: 
VAMC  
Principal Investigator: 
Michael P. Murphy, MD 
VAMC:  Roudebush VA   
 
   Indianapolis 
 
VERSION CONTROL 
Version Date   
 
Page 9 of 14 
 
Created/Updated: 
           7/15/21 
 
 
Master Template for: Roudebush  
VA Form 10-1086 
 
07/2015 
 
 
 
                                                                                                                                                                                                                                                                                                                                                          O 
Contrast can also cause injury to the kidneys and so patients with impaired kidney function will be excluded 
from enrollment.  
 
Computerized tomography (CT) scan 
 
This test can provide clear images of your aorta, and it can detect the size and shape of an aneurysm. This 
annual test is considered normal “Standard of Care.”  
 
During a CT scan, you lie on a table inside a doughnut-shaped machine. CT scanning generates X-rays to 
produce cross-sectional images of your body. Doctors may inject a dye into your blood vessels that helps your 
arteries to be more visible on the CT pictures (CT angiography). 
 
During a CT scan, you are briefly exposed to ionizing radiation. The amount of radiation is greater than you 
would get during a plain X-ray because the CT scan gathers information that is more detailed. CT scans have 
not been shown to cause long-term harm, although there may be a very small potential to increase your risk of 
cancer. CT scans have many benefits that outweigh this small potential risk. Doctors use the lowest dose of 
radiation possible to obtain the needed medical information. 
 
You will receive a special dye called a contrast material through a vein in your arm before your CT scan. 
Although rare, the contrast material can cause medical problems or allergic reactions. 
 
There is a risk of an allergic reaction, which may be serious, whenever contrast material containing iodine is 
injected. Most reactions are mild and result in a rash or itchiness. In rare instances, an allergic reaction can be 
serious, even life threatening. Contrast can also cause injury to the kidneys and so patients with impaired 
kidney function will be excluded from enrollment. 
 
Other Risks: 
There also may be side effects that we cannot predict. 
If you feel that you are experiencing problems directly related to the study treatment, you should tell the study 
doctor immediately. If you cannot do this because it is an emergency, you should get treatment and tell the 
study doctor as soon as possible.  
 
Confidentiality:   
There is a risk of loss of confidentiality. 
  
 
Payment: 
You may receive compensation for travel related expenses. If you are a veteran and your visits take place at 
the Roudebush VAMC, you will receive a meal voucher in the amount of $6.00 before each of the first three CT 


Department of Veterans Affairs 
VA Research 
Consent Form 
Subject Name:  
Date:   
Title of Study:  
A Phase I study to examine the safety and efficacy of allogeneic Mesenchymal Stromal 
Cells in suppressing inflammation in patients with small abdominal aortic aneurysm 
(AAA); IRB #1510579216 
Sponsor: 
VAMC  
Principal Investigator: 
Michael P. Murphy, MD 
VAMC:  Roudebush VA   
 
   Indianapolis 
 
VERSION CONTROL 
Version Date   
 
Page 10 of 14 
 
Created/Updated: 
           7/15/21 
 
 
Master Template for: Roudebush  
VA Form 10-1086 
 
07/2015 
 
 
 
                                                                                                                                                                                                                                                                                                                                                          O 
visits.  If you do not have transportation and live within 60 miles of the VA or IUH Methodist Hospitals you will 
be offered roundtrip, prepaid Lyft or Uber transportation for each of the first 5 study visits: Baseline through 
Month 1 visits. If you provide your own transportation to the VA or IUH Methodist Hospital you will be given a 
$30 gift card for each of the first 5 study visits: Baseline through Month 1 visits.  
 
Benefits:  
You may or may not benefit from taking part in this study. The possible benefits you may have from being in this 
study include the possibility of slowing your aneurysm’s growth. The information that we gather will help us learn 
more about stem cell therapy and could help patients in the future.  
 
Alternate Courses of Action or Treatment:  
The alternative to participating in this research study is to continue with supportive measures that include 
smoking cessation, blood pressure control, and an exercise program. Your doctor will discuss these alternatives 
with you.  
 
Medical Results: 
We may learn things about you from the study activities which could be important to your health or to your 
treatment.  If this happens, this information will be provided to you. This information may include laboratory 
results or results of a CT scan. This information will be provided to you by phone or as soon as possible.  
 
Statement of Use of Research Results:  
The results of this study may be published, but your records or identity will not be revealed 
unless required by law.  
 
You will be told about new information that may affect your health, welfare, or willingness to stay in the study.  
Your participation may be terminated by the investigator without regard to your consent if he feels that it is in 
your best interest to do so. In addition, Indiana University, the VA Medical Center, IU Health Methodist 
Hospital, or the FDA could discontinue further enrollment of people into this study. Should your participation in 
the study be stopped, a full explanation and possible alternatives will be discussed with you.  
 
Re-contact for Future Use: 
 
In the future, researchers may design a particular research study that requires use of the biological materials 
you have given as well as additional samples and/or information.  If, in the future, we would like to obtain 
additional samples and/or information, we will need to contact you to request your permission.  Please indicate 
below whether or not you give your permission for us to contact you about obtaining more information.   


Department of Veterans Affairs 
VA Research 
Consent Form 
Subject Name:  
Date:   
Title of Study:  
A Phase I study to examine the safety and efficacy of allogeneic Mesenchymal Stromal 
Cells in suppressing inflammation in patients with small abdominal aortic aneurysm 
(AAA); IRB #1510579216 
Sponsor: 
VAMC  
Principal Investigator: 
Michael P. Murphy, MD 
VAMC:  Roudebush VA   
 
   Indianapolis 
 
VERSION CONTROL 
Version Date   
 
Page 11 of 14 
 
Created/Updated: 
           7/15/21 
 
 
Master Template for: Roudebush  
VA Form 10-1086 
 
07/2015 
 
 
 
                                                                                                                                                                                                                                                                                                                                                          O 
 
I give my permission for researchers to contact me about obtaining additional samples and/or information. 
 
Yes______ No ______   Initials_________ Date __________ 
 
 
Confidentiality: 
 
Efforts will be made to keep your personal information confidential.  We cannot guarantee absolute 
confidentiality.  Your personal information may be disclosed if required by law.  Your identity will be held in 
confidence in reports in which the study may be published and databases in which the results may be stored.  
Study records that identify you will be kept confidential as required by law. Federal Privacy Regulations provide 
safeguards for privacy, security, and authorized access. Except when required by law, you will not be identified 
by name, social security number, address, telephone number, or any other direct personal identifier in study 
records disclosed outside of Indiana University or the Roudebush VA Medical Center. For records disclosed 
outside of Indiana University or the Roudebush VA Medical Center, you will be assigned a unique code number. 
The key to the code will be kept in a locked file in Dr. Murphy’s office or other appropriate research staff.  
 
Organizations that may inspect and/or copy your research records for quality assurance and data analysis 
include groups such as the investigator and his/her research associates, the Indiana University Institutional 
Review Board or its designees, , the Indiana CTSI Clinical Research Center (CRC), the Data Safety Monitoring 
Board (DSMB), the VA Research and Development Committee’s designees, and federal agencies, including 
but not limited to the Office for Human Research Protections (OHRP), the Office of Research Oversight (ORO), 
VA Office of the Inspector General (OIG), the General Accounting Office (GAO), Food and Drug Administration 
(FDA), etc., who may need to access your medical and/or research records. When you sign this form, you will 
be giving permission for these groups to see your confidential information when it is necessary. If your research 
record is reviewed by any of these groups, they may also need to review your entire medical record. 
 
Any documents we copy for this study will remain in your study file at the VA Hospital and will not be 
removed from the VA Hospital.  However, identifiable personal health information will be stored in two 
databases at Indiana University.  These two databases (one called Redcap and one called Oncore) are 
password protected, and no one other than study team personnel or authorized administrators can access 
your information stored in these databases.   
 
 
 


Department of Veterans Affairs 
VA Research 
Consent Form 
Subject Name:  
Date:   
Title of Study:  
A Phase I study to examine the safety and efficacy of allogeneic Mesenchymal Stromal 
Cells in suppressing inflammation in patients with small abdominal aortic aneurysm 
(AAA); IRB #1510579216 
Sponsor: 
VAMC  
Principal Investigator: 
Michael P. Murphy, MD 
VAMC:  Roudebush VA   
 
   Indianapolis 
 
VERSION CONTROL 
Version Date   
 
Page 12 of 14 
 
Created/Updated: 
           7/15/21 
 
 
Master Template for: Roudebush  
VA Form 10-1086 
 
07/2015 
 
 
 
                                                                                                                                                                                                                                                                                                                                                          O 
 
Retention of Research Records: 
 
Research records will be maintained by the investigator in accordance with the VHA Records 
Control Schedule. 
 
CLINICAL TRIAL POSTING  
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. Law. This 
Website will not include information that can identify you. At most, the Website will include a summary of the 
results. You can search this Web site at any time.  
 
Research Subject Costs:  
1. There will be no costs to you for any of the treatment or testing done as part of this 
research study.  Eligibility for medical care at a VA Medical Center is based upon the 
usual VA eligibility policy and is not guaranteed by participation in a research study. 
2. The study is sponsored by the principal investigator, Dr. Michael P. Murphy. 
3. You will not be required to pay for medical care or services received as a subject in a 
VA research project except as follows: 
Some veterans are required to pay co-payments for medical care and services 
provided by the VA.  These co-payment requirements will continue to apply to 
medical care and services provided by VA that are not part of this study. 
 
Compensation & Treatment for Injury:  
1. You will not receive payment for taking part in this study. 
2. The VA medical facilities shall provide necessary medical treatment to a research 
subject injured as a result of participation in a research project approved by a VA 
Research and Development Committee and conducted under the supervision of one 
or more VA employees.  This does not apply to (1) treatment for injuries due to 
noncompliance by a subject with study procedures; or (2) research conducted for VA 
under a contract with an individual or a non-VA institution. 
3. Financial compensation for research-related injuries is not available. However, by 
signing this form, you do not give up your legal rights to seek such compensation 
through the courts. 
4. You will be provided three meal vouchers for use at the VA during the study. These 
are for a late breakfast or early lunch on the three visits you will have a CT scan. 
 
 


Department of Veterans Affairs 
VA Research 
Consent Form 
Subject Name:  
Date:   
Title of Study:  
A Phase I study to examine the safety and efficacy of allogeneic Mesenchymal Stromal 
Cells in suppressing inflammation in patients with small abdominal aortic aneurysm 
(AAA); IRB #1510579216 
Sponsor: 
VAMC  
Principal Investigator: 
Michael P. Murphy, MD 
VAMC:  Roudebush VA   
 
   Indianapolis 
 
VERSION CONTROL 
Version Date   
 
Page 13 of 14 
 
Created/Updated: 
           7/15/21 
 
 
Master Template for: Roudebush  
VA Form 10-1086 
 
07/2015 
 
 
 
                                                                                                                                                                                                                                                                                                                                                          O 
 
VOLUNTARY NATURE OF STUDY: 
 
Taking part in this study is voluntary. You may choose not to take part or may leave the study at any time. 
Leaving the study will not result in any penalty or loss of benefits to which you are entitled. Your decision whether 
or not to participate in this study will not affect your current or future relations with the Roudebush VA Medical 
Center or Indiana University. If you withdraw from the study, no new information about you will be collected for 
study purposes unless the information concerns an adverse event (a bad effect) related to the study. If such an 
adverse event occurs, we may need to review your entire medical record. If you choose to withdraw from the 
study, we ask that you do so in writing to Dr. Michael Murphy, Richard L. Roudebush VA Medical Center, 1481 
W. 10th Street, Room D3009, Indianapolis, Indiana 46202. However, if you choose to withdraw from the study 
by telling us on the phone or in person, we will honor that as well.  
 
Your participation may be terminated by the investigator without regard to your consent if he feels that it is in 
your best interest to do so. In addition, Indiana University or the FDA could discontinue further enrollment of 
people into this study. Should your participation in the study be stopped, a full explanation and possible 
alternatives will be discussed with you.  
 
RESEARCH SUBJECT’S RIGHTS: 
Participation in this study is entirely voluntary.  You may refuse to participate.  Refusal to 
participate will involve no penalty or loss of rights to which individuals are entitled.  You may 
withdraw from this study at any time without penalty or loss of VA or other benefits.  You will 
receive a copy of this signed consent form. 
 
In case there are medical problems or questions, Dr. Michael Murphy can be called at 317-988-
4049 during the day and after hours you may call 317-554-0000 and ask for Dr. Murphy to be 
paged or ask for the Vascular Surgeon on call to be paged.  If any medical problems occur in 
connection with this study, the VA will provide emergency care. 
 
Please direct questions about the consent process and the rights of research subjects to the VA 
Customer Service Office at (317) 988-2602.  For questions about your rights as a research 
subject or complaints about a research study, contact the Indiana University Human Subjects 
Office at 317-278-3458 or 800-696-2949. If you have any questions about the research study or 
want to check the validity, discuss problems, concerns or obtain information or offer input, 
please call the VA Research Personnel Office at 317-988-3032. 


Department of Veterans Affairs 
VA Research 
Consent Form 
Subject Name:  
Date:   
Title of Study:  
A Phase I study to examine the safety and efficacy of allogeneic Mesenchymal Stromal 
Cells in suppressing inflammation in patients with small abdominal aortic aneurysm 
(AAA); IRB #1510579216 
Sponsor: 
VAMC  
Principal Investigator: 
Michael P. Murphy, MD 
VAMC:  Roudebush VA   
 
   Indianapolis 
 
VERSION CONTROL 
Version Date   
 
Page 14 of 14 
 
Created/Updated: 
           7/15/21 
 
 
Master Template for: Roudebush  
VA Form 10-1086 
 
07/2015 
 
 
 
                                                                                                                                                                                                                                                                                                                                                          O 
 
The study has been explained to me and all of my questions have been answered.  The risks or 
discomforts and possible benefits of the study have been described.  Other choices of available 
treatment have been explained. 
 
 
 
__________________________________ 
____________________________     _______________ 
Subject’s Signature 
Printed Name of Subject                      Date 
 
 
 
 
__________________________________ 
____________________________     _______________ 
Signature of Person Obtaining Consent 
Printed Name of Person Obtaining      Date 
Consent