Clinical trial NCT01653847
Conditions: End Stage Renal Failure With Renal Transplant
Keywords: transplant kidney renal disease
Sponsor: Northwestern University
Start date: 2013-02-01; Completion date: 2020-05-01
Enrollment: 88 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The immune system is the body's defense against infection and other disease. After transplantation, the body sees the new organ as "foreign" and tries to destroy or "reject" it. Immunosuppressive medications help to prevent the immune system from attacking a transplanted organ. The primary purpose of this study is to investigate the impact of two maintenance immunosuppressive regimens. Subjects who enroll in this study will be randomly selected to have tacrolimus and everolimus (group 1) or tacrolimus and mycophenolate mofetil (group 2) as their immunosuppression medication.

This study will enroll adult patients who are scheduled to receive a kidney transplant.

The study is designed to understand the mechanisms of Everolimus in regards to kidney function in transplant recipients. The investigators hypothesis is that decreased exposure to Tacrolimus to the immune system will then translate in better renal allograft function.

Detailed description:
Immunosuppressive therapy with the calcineurin inhibitors (CNI) Cyclosporine (CsA) and Tacrolimus (Tac), have radically changed the field of organ transplantation. Ironically, although extensively and effectively used for kidney transplantation and other solid organ transplants, CsA and Tac cause important adverse renal side effects: acute and chronic renal dysfunction, hemolytic-uremic syndrome, hypertension, electrolyte disturbances and tubular acidosis. Chronic nephrotoxicity from CNI has been implicated as a principal cause of post-transplant renal dysfunction and it is characterized by an irreversible and progressive tubular atrophy, interstitial fibrosis, and focal hyalinosis of small renal arteries and arterioles. Furthermore, this class of medications is associated also, by blocking Interleukin-2 (IL2) production, with negative impact on regulatory T cells (T-Regs) generation (an important subpopulation of T helper cells that has been associated with positive immunomodulation and donor specific hypo responsiveness).

In renal transplant recipients, complete avoidance of calcineurin inhibitors from the time of renal transplant surgery has been associated with increased incidence of acute cellular rejection, and the combination of mammalian target of rapamycin (mTOR) inhibitors with full dose CNI has been shown to be synergistically nephrotoxic and it has been associated with poor graft outcome. CNI conversion to mTOR inhibitors, at different time point post-transplant, has been tested with promising results, by different investigators and by the investigators group. The investigators have shown that in a Prednisone-free immunosuppression, conversion from Tacrolimus to mTor inhibitors at different time point post transplant is safe, it is not associated with an increased risk of acute rejection and more importantly it is associated with an a persistent increase of regulatory T cells (Data presented at the American Transplant Congress (ATC) 09 and 2010) Recently the A2309 study allowed Everolimus to be FDA approved. The A2309 was a study designed to combined reduced dose Cyclosporine+Everolimus. Interesting the reduced exposure to Cyclosporine was not associated with an increase rate of albumin-creatinine ratio (ACR) and renal allograft function was well maintained compared to the control group. The A2309 opens then an important question regarding the mechanism(s) that can explain the efficacy of a low dose CNI with an mTOR inhibitor in preventing acute allograft rejection.

The present proposal is designed to understand the mechanisms of the synergistic effect(s) of low dose CNI and mTOR inhibitors (Everolimus) in controlling allo-reactive T and B cells while expanding T-Regs.

The investigators hypothesis based in published data and from their laboratory (see preliminary data-Supportive documents), is that mTOR inhibitors allow expansion of T-Regs and low exposure of CNI is sufficient to control allo-reactive T cells. Decrease exposure to CNI and concomitant increase of T-Regs will then translate in better renal allograft function and histology.

Arms: arm 1: This group will receive a standard dose Tacrolimus and MMF. This will follow standard of care protocol at Northwestern Memorial Hospital's Comprehensive Transplant Center. arm 2: This group will receive a low dose Tacrolimus with concentration controlled Everolimus arm 3: One time blood samples will be collected from kidney donors to recipients in this study
Interventions: intervention 1: Tacrolimus with MMF intervention 2: Group 2: Tacrolimus with Everolimus.
Intervention descriptions: intervention 1: Standard dose Tacrolimus and MMF. This will follow standard of care procedures at Northwestern Memorial Hospital's Comprehensive Transplant Center. MMF trough or area under the concentration time curve (AUC) shall not be used to adjust dosing. In this group, Tacrolimus will be initiated according to our practice. The Tacrolimus dose will be adjusted from day 3 on to achieve a target whole blood trough concentration of 8 ng/mL to 10 ng/mL. From month 2 until Month 6, the target Tacrolimus trough level will be reduced to 6 ng/mL to 8 ng/mL. After month 6, the target level of Tacrolimus will be reduced to 4 ng/mL to 8 ng/mL. intervention 2: From day 5 on, the starting dose of Everolimus (0.75 mg bid) will be increased if the trough level is \< 3 ng/mL, or reduced if the trough level is \> 8 ng/mL. Tacrolimus will be initiated according to our practice. In this treatment arm, the Tacrolimus dose will be adjusted from day 3 on, to a target whole blood trough concentration of 4 ng/mL to 7 ng/mL. From month 2 until Month 6, the target Tacrolimus trough level will be 3 ng/mL to 6 ng/mL. After month 6, the Tacrolimus dose should be adjusted in order to achieve a target trough level of 2 ng/mL to 5 ng/mL. MMF dose will be initiated as 1 g b.i.d. (2 g/day). Adjustments should be made for adverse events including but not limited to gastrointestinal intolerance and a decrease in white blood cell (WBC).

Protocol documents:
Prot_SAP_000.pdf: 
 
Investigator’s Name: Lorenzo Gallon MD. 
Associated Professor of Medicine 
UNOS Medical Director  
Institution: Northwestern University Feinberg School of 
Medicine 
Address: 676 North St. Clair Suite 1900,  
Chicago, IL 60611 
Tel: 312-695-4457 
Email: l-gallon@northwestern.edu 
Version: 11-10-2016 
ePRISM ID: IIRP-1275 
 
 
Title of study 
Impact of two prednisone-free maintenance immunosuppressive regimens with 
reduced dose FK506+Everolimus vs. standard dose FK506+MMF on subpopulation 
of T and B cells, renal allograft function and gene expression profiles in renal allograft 
biopsies at 12, 24 and 36 months post-transplant. Prospective single center study in 
recipients of renal transplant allograft.  
 
Study purpose and rationale 
Immunosuppressive therapy with the calcineurin inhibitors (CNI) cyclosporine (CsA) 
and tacrolimus (Tac), has radically changed the field of organ transplantation. 
Ironically, although extensively and effectively used for kidney and other solid organ 
transplants, CsA and Tac cause significant adverse renal side effects: acute and 
chronic renal dysfunction, hemolytic-uremic syndrome, hypertension, electrolyte 
disturbances and tubular acidosis. Chronic nephrotoxicity from CNI has been 
implicated as a principal cause of post-transplant renal dysfunction. It is 
characterized by an irreversible and progressive tubular atrophy, interstitial fibrosis, 
and focal hyalinosis of small renal arteries and arterioles. Furthermore, by blocking 
IL2 production, this class of medications is also associated with a negative impact on 
generation of regulatory T cells, or (Tregs). (Tregs are an important subpopulation of 
helper T cells that has been associated with positive immunomodulation and donor 
specific hypo-responsiveness).  
 
In renal transplant recipients, complete avoidance of calcineurin inhibitors from the 
time of renal transplant surgery has been associated with increased incidence of 
acute cellular rejection. The combination of mTOR inhibitors with full dose CNI has 
been shown to be synergistically nephrotoxic, and has been associated with poor 
graft outcome. We and other investigators have tested conversion from CNI to mTOR 
inhibitors with promising results. We have shown that in a prednisone-free 
immunosuppression regimen, conversion from tacrolimus to mTor inhibitors is safe, 
and not associated with an increased risk of acute rejection. More importantly, we 
have shown that it is associated with a persistent increase of regulatory T cells (Data 
presented at ATC 09 and 2010). 
 
Recently, the A2309 study led to FDA-approval of Everolimus. The A2309 was a 
study designed to combine reduced dose CsA+Everolimus. Interestingly, the reduced 
exposure to CsA was not associated with an increased rate of ACR; renal allograft 
function was well maintained when compared to that of the control group. This study 


Investigator’s name: Lorenzo Gallon 
 
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study leads us to question the mechanism(s) behind the efficacy of a low dose CNI 
with an mTOR inhibitor in preventing acute allograft rejection. 
   
The present proposal is designed to investigate the mechanisms of the synergistic 
effect(s) of low dose CNI and mTOR inhibitors (Everolimus) in controlling alloreactive 
T and B cells while expanding Tregs.   
 
Our hypothesis, based on published data and our laboratory results (see preliminary 
data-Supportive documents), is that mTOR inhibitors allow expansion of Tregs and 
that low exposure to CNI is sufficient to control alloreactive T cells. Decreased 
exposure to CNI and concomitant increase of Tregs will then translate to improved 
renal allograft function and histology. 
 
Objectives  
The overall aim of the present study is to prospectively investigate the impact of two 
maintenance immunosuppressive regimens (both prednisone-free) on 
subpopulations of T and B cells and on renal allograft function at 12, 24 and 36 
months post-randomization. One regimen combines low CNI exposure (tacrolimus) 
with concentration controlled Everolimus, and the second combines standard dose 
CNI (Tacrolimus) with MMF. 
 
The primary endpoints of the study are to: 1) evaluate the impact of the two 
maintenance immunonusuppressive regimens on T cells subpopulations, including 
regulatory T cells and B cell subpopulations, at different time points post renal 
transplant, and2) determine the impact of the two regimens on renal allograft function 
at 12, 24 and 36 months post-randomization (post-transplant). Secondary endpoints 
of the study are to: 1) evaluate the impact of the two regimens on allograft 
immunohistopathology gene expression profiles and graft infiltrating cells (memory T 
cell (CD4+ or CD8+ CD45RO+), TREG (CD4+FoxP3+), memory B cell (CD19+CD27+)) at 
12 and 24 months in renal allograft biopsies, and 2) evaluate the impact of the 
regimens on acute rejection, graft loss and death at 12, 24 and 36 months post-
transplant. 
 
Population 
The study will be conducted at Northwestern University Feinberg School of 
Medicine/Northwestern Memorial Hospital, and subjects will be recruited during visits 
to the Comprehensive Transplant Center. We plan to enroll and randomize recipients 
and their respective donors until 40 recipients have started the study drug to which 
they were randomized. As of January 2014, 3 recipients randomized to the 
experimental arm and 1 randomized to the control arm were withdrawn prior to 
dosing due to surgical complications. Replacement pairs will be enrolled, bringing the 
prospective enrollment to a minimum of 44 donor/recipient pairs (at least 88 total 
subjects).   
 
Inclusion Criteria:  


Investigator’s name: Lorenzo Gallon 
 
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1) Adults between 18 and 70 years of age 
2) Either gender and of any ethnic background 
3) Single-organ recipients (kidney only) 
4) Able to understand the protocol and provide informed consent. 
5) Recipient of living donor kidney transplants 
6) PRA<20% 
 
Exclusion criteria: 
1) End Stage Renal Disease (ESRD) secondary to primary FSGS (focal segmental 
glomerulonephritis). 
2) Inability to fully understand the purpose of the study and the inability to sign the 
informed consent 
3) A significant or active infection 
4) Pregnant or nursing females 
5) History of severe hyperlipidemia not controlled with statins, subjects with 
Cholesterol > 400mg/dl 
6) Platelet count <100,000mm3, WBC < 2,000mm3 (or clinical practice) 
7) Any surgical, medical or psychiatric condition, other than the current transplant, 
which in the opinion of the investigator precludes enrollment into this trial 
 
Number of centers & subjects  
Northwestern University Feinberg School of Medicine /Northwestern Memorial 
Hospital. 
 
Investigational and reference therapy   
Everolimus. Dose: 0.75mg PO BID (concentration controlled). 
 
Study duration   
We expect the total duration for this study not to exceed 2 years from the date of the 
last subject’senrollment. 
 
Study design  
Renal Transplant Recipients: 
All recipients will receive the same induction immunotherapy at time of transplant.   : 
Campath (30mg IV x1) will be administered at the time of surgery. 
Methylprednisolone (500 mg IV) will be administered on the day of transplant and on 
days 1 (250 mg IV), and 2 (125 mg IV) post-transplant. No further steroids will be 
given post-transplant unless indicated by the following medical conditions: acute 
renal allograft rejection, renal diseases necessitating the use of steroids, and other 
systemic diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus 
(SLE), and asthma.  
 
Maintenance immunosuprression is administered according to the 1:1 randomization 
at time of enrollment:  20 subjects will begin standard dose tacrolimus and MMF 
(control arm) 


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Tacrolimus will be initiated according to our practice. The dose will be adjusted from 
day 3 on to achieve a target whole blood trough concentration of 8 ng/mL to 10 
ng/mL.  From month 2 until Month 6, the target tacrolimus trough level will be 
reduced to 6 ng/mL to 8 ng/mL.   After month 6, the target level will be reduced to 4 
ng/mL to 8 ng/mL.   
 
MMF dose will be initiated as 1 g b.i.d. (2 g/day).  Adjustments should be made for 
adverse events including but not limited to gastrointestinal intolerance and a 
decrease in WBC.  MMF trough or AUC shall not be used to adjust dosing.   
 
Twenty (20) subjects will begin low dose tacrolimus with concentration 
controlled everolimus (treatment arm) 
Tacrolimus will be initiated according to our practice.  In this treatment arm, the 
Tacrolimus dose will be adjusted from day 3 on, to a target whole blood trough 
concentration of 4 ng/mL to 7 ng/mL.  From month 2 until Month 6, the target 
Tacrolimus trough level will be 3 ng/mL to 6 ng/mL.  After month 6, the Tacrolimus 
dose should be adjusted in order to achieve a target trough level of 2 ng/mL to 5 
ng/mL.   
 
From day 5 on, the starting dose of Everolimus (0.75 mg bid) will be increased if the 
trough level is < 3 ng/mL, or reduced if the trough level is > 8 ng/mL.  
 
All drugs will be administered in an open label fashion. 
 
The following transplant recipient data will be collected at the time of randomization:. 
Demographics: Age at transplantation, sex and race. 
Causes of end-stage renal disease 
Transplant related information: donor age, histocompatibility and cross match data, 
viral serology, history of acute rejection and delayed graft function, use of ACEI 
and/or ARB, level of renal allograft function - estimated GFR ( e-GFR(12) using 
MDRD formula, proteinuria.  
 
Blood samples will be obtained prior to randomization from all renal transplant 
recipients for baseline T and B cell functional activity and characterization of the cell 
subpopulations by flow cytometry.  
 
-All recipients will be routinely followed at our Transplant center with post-transplant 
labs (SMA7, CBC, and relevant immunosuppression trough levels).  
 
Additional blood will be collected and analyzed for the study at 3, 6, 12, 24 and 36 
months post-randomization. If the final blood sample cannot be drawn at the 36 
month timepoint, it may be drawn up to 50 months post-transplant. These samples 
will be used to investigate the impact of the two maintenance immunonusuppressive 
regimens on subpopulation of T cells In comparison with baseline levels. Specifically, 


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we will look at regulatory T cells (Treg: Foxp3+CD4+ CD25bright+) that could have 
been generated via the two maintenance immunonusuppressive regimens, and 
correlate the generation of with their function.  
 
RNA from peripheral blood will be also collected and stored for post-hoc analyses of 
T and B-cell immunoresponse gene expression via gene arrays.  
 
Kidney biopsy samples will be collected with standard-of-care samples at time of 
transplant (back table), 3 months, 12 months and at 24 months post-transplant. 
These will help evaluateand compare the impacts of the two maintenance 
immunonusuppressive regimens on allograft immunohistopathology.  Gene 
expression profiles will also be analyzed.  These samples will be processed in the 
principal investigator’s research laboratory.   
 
Both groups of subjects will be followed through 36-months post-randomization. In 
addition to monitoring renal allograft function, we will evaluate the incidence of acute 
rejection, subject and graft survival, incidence of hypertension (HTN), malignancies, 
opportunistic infections and post-transplant diabetes mellitus (DM). 
 
Donors: 
Blood samples from donor subjects will also be obtained at either the time of 
randomization or post-surgery during standard-of-care follow-up appointments These 
donor leukocytes will be used as stimulator cells in studies of functional activity of 
recipient T-cells.  These samples will be processed in the principal investigator’s 
research laboratory.   
 
 
 
 
 


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Safety:  
Safety Endpoints: The primary safety endpoints will be assessed on the AEs and 
SAEs that are observed throughout the trial. 
For the purpose of this clinical trial, the National Cancer Institute Common 
Terminology Criteria for Adverse Events v3.0 (CTCAE), dated December 12, 2003, 
will be used to grade all adverse events. 
 
Recording of Adverse Events 
At each contact with the subject, the investigator/member of investigator’s team will 
seek information on adverse events by specific questioning and, as appropriate, by 
examination.  Information on all adverse events will be recorded in the source 
document, and also in the appropriate adverse event module of the case report form 
(CRF).  All clearly related signs, symptoms, and abnormal diagnostic procedures 
results should recorded in the source document, though should be grouped under 
one diagnosis. 
 
All adverse events occurring during the study period will be recorded.  The clinical 
course of each event should be followed until resolution, stabilization, or until it has 
been determined that the study treatment or participation is not the cause.  Serious 
adverse events that are still ongoing at the end of the study period must be followed 
up to determine the final outcome.  Any serious adverse event that occurs after the 
study period and is considered to be possibly related to the study treatment or study 
participation will be recorded and reported immediately. 
 
Stopping Rules 
Subjects developing post-transplant infections (i.e., UTI, CMV, HSV, EBV, HCV, 
HBV, HIV,PCP), that in the opinion of the investigator are detrimental to the subject 
and his/her participation in this research trial, will be stopped from participating in this 
study..  
 
Patient Authorization: This study is to be conducted according to US and international 
standards of Good Clinical Practice (FDA Title 21 part 312 and International 
Conference on Harmonization guidelines), applicable government regulations and 
Institutional research policies and procedures. 
 
This protocol and any amendments will be submitted to a properly constituted 
independent Institutional Review Board (IRB), (Northwestern University Institutional 
Review Board), in agreement with local legal prescriptions, for formal approval of the 
study conduct.  The decision of the IRB concerning the conduct of the study will be 
made in writing to the investigator and a copy of this decision will be provided to the 
investigator/sponsor before commencement of this study.  The investigator will place 
a list of IRB members and their affiliate in the regulatory binder for the clinical trial. 
 
All subjects for this study will be provided with a printed consent form describing this 
study and providing sufficient information for subjects to make an informed decision 


Investigator’s name: Lorenzo Gallon 
 
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about their participation in this study. This consent form will be submitted with the 
protocol for review and approval by the IRB for the study.  The formal consent of a 
subject, using the IRB-approved consent form, will be obtained before the subject is 
submitted to any study procedures. This consent form will be signed by the subject 
and the investigator-designated research professional obtaining the consent.  The 
subject will be given a signed copy of the informed consent for their records. 
 
Statistical analysis:   
The primary endpoints of the study are graft function and subpopulations of T cells, 
including regulatory T cells and B cell subpopulations at 3, 6, 12, 24 and 36 months 
post kidney transplant. The secondary endpoints of the study include 1) incidence of 
acute rejection, graft loss, and death at 12,24 and 36 months post kidney transplant; 
2) allograft immunohistopathology and gene expression profiles at 12 and 24 months 
post kidney transplant. 
 
We will run univariate and bivariate analyses for all variables prior to our main 
analyses. We will evaluate continuous variables using t-tests or F-tests and 
categorical variables using c2. We will examine data distributions and test all 
variables for linear relationships or non-linear relationships.  
 
Descriptive statistics (means, standard deviation, frequency) and correlations (both 
Pearson and Spearman) among variables will be calculated for preliminary data 
assessment. 
Necessary transformation and imputations will be carried out based on the raw data 
distribution.  
 
As missing data are inevitable in a longitudinal study, we will determine whether 
missing data are MCAR (data are missing completely at random), MAR (data are 
missing at random), or NMAR (not missing at random). If missing data are MCAR or 
MAR, it is likely that the standard multivariate computations using PROC MI (multiple 
imputations) will not result in biased standard error estimates.   However, if missing 
data are NMAR, we will use the "pattern mixture" approach to compute a weighted 
average of the parameters that are associated with the missing data to estimate what 
the data would have been. 
 
For the primary objective, we hypothesize that subjects receiving low dose CNI with 
mTOR inhibitor (Everolimus) will exhibit significantly greater graft function and higher 
numbers of regulatory T cells as compared to the standard dose CNI+MMF group.  
 We will utilize both repeated-measures ANOVA and random mixed effect models to 
compare the trajectory change in graft function and proportion of regulatory T cells 
over 12, 24 and 36 months between the two experimental groups. The method of 
estimation will be maximum likelihood (ML).   
 


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A variety of covariance structures (first order regressive, compound symmetry, 
Toeplitz, variance components, unstructured) will be carefully examined and 
compared using the best fitting statistics, such as Akaike’s Information (AIC) and 
Bayesian Information Criteria (BIC). These statistics are likelihood functions and can 
be compared across models. If, in spite of randomization, distributions of subjects’ 
baseline characteristics are found to be different between the two experimental 
groups, these variables will be entered as covariates in the statistical analysis. 
 
For the secondary endpoints, we will use logistic regression, Kaplan-Meier method, 
and Cox proportional hazards models to analyze time-to-event outcomes (acute 
rejection, graft failure, and death). For allograft immunohistopathology and gene 
expression profile outcomes, we will first develop a comprehensive immune profile of 
each participant by longitudinal analysis of frequency and function of T and B cell 
subsets. We will examine how these correlate with immunohistopathology and 
alloantibody production using Pearson or Spearman correlations. We will compare 
correlation coefficients between the two experimental groups using Z -tests to 
determine the distinct effects of each treatment arm.  We will also compare the 
trajectory changes in cell populations and antibody production over 12, 24 and 36 
months using both repeated measures ANOVA and random mixed effect models. All 
tests will be two-sided, and an error rate of α <0.05 will be considered statistically 
significant. All data analyses will be performed using SAS 9.2 statistical software 
(SAS Inc., Cary, NC).      
 
Sample size and power   
We calculated our sample power for the two primary endpoints based on our clinical 
experience and small pilot data. Using a two-tailed α of 0.05, the anticipated effect 
sizes corresponding to each specific aim between the two treatment arms were 
calculated using a minimum of 80% statistical power and assumed 10% attrition at 12 
months.  
 
For the sample size of n= 20 in each group, the proposed study will have a power of 
0.82 and 0.99 to detect effect size of 1.0 and 2.0 for graft function and % regulatory T 
cell change, respectively, between the two treatment arms.  Because this is a pilot 
study, we do not consider the statistical power of secondary outcomes; It is 
anticipated that a much larger sample size will be needed in order to achieve 
statistical power for the secondary endpoints in this proposed study. 
 
Evaluation schedule:   
 
 
Supportive documents and preliminary data: 
 
Conversion from CNI to Mtor-based immunosuppression after kidney transplant 
changes the frequency and phenotype of Tregs 
 


Investigator’s name: Lorenzo Gallon 
 
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Abstract ATC 2010: 
Lorenzo Gallon, Yuming Yu, Nader Najafian, Xuemei Huang, Giovanna La Monica, James Mathew, Josh 
Miller, Joseph Leventhal, Luting Xu Medicine/Comprehensive Transplant Center, Northwestern University, 
Chicago; Medicine, Harvard University 
 
Subpopulation of T helper cells (Th1, Th17, and Treg) can play a major role in promoting rejection or can facilitate 
regulatory immune-mechanisms that can help the development of a pro-tolerant state towards the transplant. 
Little is known about the impact of immunosuppressive (IS) drugs on allospecific T cell subpopulations. Methods: 
A two-step culture system was used. Alloreactve memory CD4+ T cells were first generated in MLR culture with 
responding CD4+CD45RA+ nave T cells and allogeneic CD14+ monocytes. Memory CD4+ T cells, from the 
primary MLR, were enriched and re-stimulated by co-culturing with autologous CD14+ monocytes in the presence 
of antigenic stimulation of anti-CD3 to increase the frequency of Th1,Th17 and Treg cells. Two different IS agents, 
Tacrolimus (Tac) and Sirolimus (SRL) were added to the second culture alone or in combination at different 
concentrations. The effects on the generation of Th1, Th17, Treg cells from alloreactive memory T cells 
(CD4+CD45RO+) were then determined by intracellular cytokine staining. Results: After secondary stimulation, 
there was up to 10-fold increase, compared to primary stimulation, in the % of Th1, Th17 and Treg cells. Tac at 
low doses, significantly blocked the productions of IFN-  (Th1) and IL-17 (Th17), while SRL even at high 
concentration (10ng/ml or 20ng/ml) had minimal effect on IFN-  and IL-17 production (see top panels of figure). 
FOXP3 expression (Treg) was markedly increased in SRL compared to Tac (see bottom panel). When Tac and 
SRL were used in combination and at different concentrations, we found that Tac at 2-5 ng/ml with SRL at 2.5-
10ng/ml achieved the maximal effect in inhibiting the production of IFN-  and IL-17 while maintaining a high level 


Investigator’s name: Lorenzo Gallon 
 
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of FOXP3 expression. 
 
Conclusions: Tac and SRL have differential effects on subpopulation of T helper cells. These findings can help to 
guide the clinical use of IS drugs to promote Treg expansion while controlling Th1 and Th17 responses. 
Keywords: Immunosuppression; Sirolimus (SLR); Calcineurin; T cell activation 
Oral Session: Late-Breaking Basic Abstract Session (10:45 AM-12:15 PM) 
 
Selected references to support this application: 
 
1. 
Bennett WM. Insights into chronic cyclosporine nephrotoxicity. Int J Clin 
Pharmacol Ther 1996, 34:515. 
2. 
Bennett WM, DeMattos A, Meyer MM, Andoh T, Barry JM. Chronic 
cyclosporine nephropathy: the Achilles' heel of immunosuppressive therapy. 
Kidney Int 1996, 50:1089. 
3. 
Myers BD: Cyclosporine nephrotoxicity. Kidney Int 1986, 30:964. 
4. 
Puschett JB, Greenberg A, Holley J, McCauley J. The spectrum of 
cyclosporine nephrotoxicity. Am J Nephrol 1990, 10: 296. 
5. 
Myers BD, Ross J, Newton L, Luetscher J, Perlroth M. Cyclosporine-
associated chronic nephropathy. N Engl J Med 1984, 311:699. 
6. 
Goldstein DJ, Zuech N, Sehgal V, Weinberg AD, Drusin R, Cohen D. 
Cyclosporine-associated end-stage nephropathy after cardiac transplantation: 
incidence and progression. Transplantation 1997, 63:664. 
7. 
Hornberger J, Best J, Geppert J, McClellan M. Risks and costs of end-stage 
renal disease after heart transplantation. Transplantation 1998, 66:1763. 


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8. 
Ojo AO, Held PJ, Port FK, et al. Chronic renal failure after transplantation of a 
nonrenal organ. N Engl J Med 2003, 349:931. 
9. 
Burdmann EA, Andoh TF, Yu L, Bennett WM. Cyclosporine nephrotoxicity. 
Semin Nephrol 2003, 23:465. 
10.  
Nankivell B., Alexander S. Rejection of the kidney allograft. New England 
Journal of Medicine 363:1451-1462 (2010). 
11. 
Kim IK, Bedi DS, Denecke C, Ge X, Tullius SG. Impact of innate and adaptive 
immunity on rejection and tolerance. Transplantation 86:889-94 (2008) 
12. 
Meier-Kriesche HU, Shold JD, Srinivas TR, Kaplan B. Lack of improvement in 
renal allograft survival despite a marked decrease in acute rejection rates over 
the most recent era. Am J Transplant 4:378-83 (2004) 
13 
Nankivell B, Borrows R, Fung C, et al. The natural history of chronic allograft 
nephropathy. N Engl J Med 349:2326:2333 (2003).  
14 
Pontrelli P, Rossini M, Infante B, et al. Rapamycin inhibits PAI-1 expression 
and reduces interstitial fibrosis and glomerulosclerosis in chronic allograft 
nephropathy. Transplantation 85: 125-134 (2008). 
15 
Lebranchu Y, Thierry A, Toupance O, Westeel P, Etienne I, Thervet E, Moulin 
B, Frouget T, Le Meur Y, Glotz D, Heng A, Onno C, Buchler M, Girardot-
Seguin S, Hurault de Ligny B. Efficacy on renal function of early conversion 
from cyclosporine to sirolimus 3 months after renal transplantation: concept 
study. Am J Transplant 9:1115:1123 (2009) 
16 
Servais A, Meas-Yedid V, Toupance O, Lebranchu Y, Thierry A, Moulin B, 
Etienne I, Presne C, Hurault de Ligny B, Le Pogamp P, Le Meur Y, Glotz D, 
Hayem C, Olivo Marin J, Thervet E. Interstitial fibrosis quantification in renal 
transplant recipients randomized to continue cyclosporine or convert to 
sirolimus.   Am J Transplant 9: 2552:2560 (2009) 
17 
Chhabra D, Grafals M, Cabral B, Leventhal J, Parker M, Gallon L. Late 
conversion of tacrolimus to sirolimus in a prednisone-free immunosuppression 
regimen in renal transplant patients. Clin Transplant 24 (2):199:206. 2010. 
18.  
Levitsky J, Gallon L, Miller J, Tambur A, Leventhal J, Flaa C, Huang X, Sarraj 
B, Wang E, Mathew JM. Allospecific regulatory effects of sirolimus and 
tacrolimus in the human mixed lymphocyte reaction. Transplantation 27;91(2): 
199-206, 2011 
19. 
Battaglia, M., et al. Rapamycin and interleukin-10 treatment induces T 
regulatory type 1 cells that mediate antigen-specific transplantation tolerance. 
Diabetes 55, 40-49 (2006). 
20. 
Battaglia, M., Stabilini, A. & Roncarolo, M.G. Rapamycin selectively expands 
CD4+CD25+FoxP3+regulatory T cells. Blood 105, 4743-4748 (2005). 
21. 
Nikolaeva, N., Bemelman, F.J., Yong, S.L., van Lier, R.A. & ten Berge, I.J. 
Rapamycin does not induce anergy but inhibits expansion and differentiation 
of alloreactive human T cells. Transplantation 81,445-454 (2006). 
22. 
Turnquist, H.R., et al. Rapamycin-conditioned dendritic cells are poor 
stimulators of allogeneic CD4+ T cells, but enrich for antigen-specific Foxp3+ 
T regulatory cells and promote organ transplant tolerance. J Immunol 178, 
7018-7031 (2007). 


Investigator’s name: Lorenzo Gallon 
 
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Everolimus 
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Valmori, D., et al. Rapamycin-mediated enrichment of T cells with regulatory 
activity in stimulated CD4+ T cell cultures is not due to the selective expansion 
of naturally occurring regulatory T cells but to the induction of regulatory 
functions in conventional CD4+ T cells. J Immunol 177, 944-949 (2006). 
24. 
Baan, C.C., et al. Differential effect of calcineurin inhibitors, anti-CD25 
antibodies and rapamycin on the induction of FOXP3 in human T cells. 
Transplantation 80, 110-117 (2005). 
25. 
Gao, W., et al. Contrasting effects of cyclosporine and rapamycin in de novo 
generation of alloantigen specific regulatory T cells. Am J Transplant 7, 1722-
1732 (2007). 
26. 
Bestard O, Cruzado J, Mestre M, Caldes A, Bas J, Carrera M, Torras J, Rama 
I, Moreso F, Seron D, Grinyo J. Achieving donor-specific hyporesponsiveness 
is associated with FoxP3+ regulatory T cell recruitment in human renal 
allograft infiltrates. Journal of Immunology 179 4901:4909 (2007) 
27. 
Alvarez C, Opelz G, Garcia L, Susal C. Expression of regulatory T-cell-related 
molecule genes and clinical outcomes in kidney transplant recipients. 
Transplantation 87:857-863 (2009) 
28. 
Noris M, Casiraghi F, Todeschini M, Cravedi P, Cugini D, Monteferrante G, 
Aiello S, Cassis L, Gotti E, Gaspari F, Cattaneo D, Perico N, Remuzzi G. 
Regulatory T cells and T cells depletion: role of immunosuppressive drugs. 
JASN 18: 1007-1018 (2007) 
29. 
Ruggenenti P, Perico N, Gotti E, et al. Sirolimus versus cyclosporine therapy 
increases circulating regulatory T cells, but does not protect renal transplant 
patients given alemtuzumab induction from chronic allograft injury. 
Transplantation, 84: 956-964 (2007) 
30. 
Wang Y, Camirand G, Lin Y, Froicu M, Deng S, Shlomchik W, Lakkis F, 
Rothstein D. Regulatory T cells require mammalian target of rapamycin 
signaling to maintain both homeostasis and alloantigen-driven proliferation in 
lymphocyte-replete mice. Journal of Immunology 186:000-000 (2011) 
31. 
Valujskikh A. The challenge of inhibiting alloreactive T cell memory. Am J 
Transplantation 6: 647-651 (2006) 
32. 
Valujskikh A, Baldwin III W, Fairchild R. Recent progress and new 
perspectives in studying T cell responses to allografts. Am J Transplantation 
10: 1117-1125 (2010) 
33. 
Pearl J, Parris J, Hale D, Hoffmann S, Bernstein W, McCoy K, Swanson S, 
Mannon R, Roederer M, Kirk A. Immunocompetent T cells with a memory-like 
phenotype are the dominant cell type following antibody-mediated T-cell 
depletion. Am J Transplantation 5:465-474 (2005) 
34. 
Araki K, Turner A, Shaffer V, Gangappa S, Keller S, Bachmann M, Larsen C, 
Ahmed R. mTOR regulates memory CD8 T-cell differentiation. Nature 
460:108-112 (2009) 
35. 
Ferrer I, Wagener M, Robertson J, Turner A, Araki K, Ahmed R, Kirk A, Larsen 
C, Ford M. Cutting edge: Rapamycin augments pathogen-specific but not graft-
reactive CB8+ T cell responses. The Journal of Immunology 185:2004-2008, (2010) 

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Northwestern University 
Comprehensive Transplant Center 
Consent Form and HIPAA Authorization for Research 
 
 
PROTOCOL TITLE:  Impact of two prednisone-free maintenance immunosuppressive regimens 
with reduced dose FK506+Everolimus vs. standard dose FK506+MMF on subpopulation of T and 
B cells, renal allograft function and gene expression profiles in renal allograft biopsies at 12, 24 and 
36 months post-transplant.  Prospective single center study in recipients of renal transplant allograft 
(Protocol Version 26Oct2017).  
 
PRINCIPAL INVESTIGATOR:  Lorenzo Gallon, MD  
 
SUPPORTED BY:  Novartis Pharmaceuticals 
 
Conflict of Interest Disclosure 
The following disclosure is made to give you an opportunity to decide if this relationship will affect 
your willingness to participate in this research study:  
 
If your doctor is also the person responsible for this research study, please note that he is interested 
in both your clinical care and the conduct of this research study.  You have the right to discuss this 
study with another person who is not part of the research team before making your decision whether 
or not to be in the study. 
 
Introduction 
You are being asked to take part in a research study. This document has important information 
about the reason for the study, what you will do if you choose to take part, and the way we, 
Northwestern University, would like to use information about you and your health. 
 
What is the reason for doing this study? 
You are being asked to be part of this research study because you are going to receive a kidney 
transplant.   
 
The immune system is your body’s defense against infection and other disease. After 
transplantation, the body sees the new organ as “foreign” and tries to destroy or “reject” it.  
Immunosuppressive medications help to prevent your immune system from attacking your 
transplanted organ. The primary purpose of this study is to investigate the impact of two 
maintenance immunosuppressive treatment plans on your immune system.    
 
The immunosuppressants used in this study are mycophenolate mofetil, tacrolimus and everolimus. 
All of these medications are approved for use by the United States Food and Drug Administration 
(FDA) to prevent your body from rejecting the kidney you receive during your kidney transplant 
surgery.   
 
Randomization: 
In this research study, you will be randomly placed into one of the two following groups. You will 
be placed into either group by chance using a process similar to the flip of a coin. Neither you nor 
the study staff will select what group you will be in. 


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(Group 1): tacrolimus and mycophenolate mofetil 
(Group 2): tacrolimus and everolimus  
 
What you will do if you choose to be in this study?  
If you decide to take part in this study, your participation will last for about 3 years or 36 months 
after your transplant date, and will include 5 study visits.  Visits for this study will occur at pre-
transplant and then 3, 6, 12, 24 and 36 months post-transplant. If it is not possible for the final visit 
to occur at 36 months, this visit may take place up to 50 months post-transplant.   
 
Screening/Baseline Data and Sample Collection 
Once you have read and signed this consent form, information about you (age, gender and race) will 
be collected by study staff. We will collect additional data from your medical record, as explained 
on the following page. 50 mL or about 3.5 tablespoons of blood and a sample of your urine will be 
collected for research on the day of your surgery, before you receive your transplant. 
 
At the time of transplant, a kidney biopsy will be performed as standard of care.  We will collect a 
piece of tissue from this biopsy for research purposes. 
 
Follow-Up Visits 
You will be followed at the transplant center and receive similar care as participants not taking part 
in a research study.  This study was designed so that follow-up information is collected when you 
would already be in the clinic as part of your normal care. All subjects in this study will be required 
to visit the clinic for study-related visits at the time points listed above.  In the event that you are not 
scheduled for a 3, 6 12, 24 or 36 month visit as standard-of-care, we would ask you to come 
specifically for the study, at no additional cost to you. On average, a research-only visit may last 
from 15 to 30 minutes in length. 
 
At each research follow-up, you will answer questions regarding your health.  Blood and urine 
samples will be collected for research tests at each visit, in addition to any required for your normal 
care.  About 50 mL or 3.5 tablespoons of blood will be collected specifically for research.  
Tests strictly associated with this research protocol also involve kidney biopsy tissue. Kidney 
biopsies are done for standard of care once at 3 months, 12 months and 24 months post-transplant, 
and a piece of the kidney biopsy tissue from each of these visits will be used for our research study.   
 
Medical History 
We will review your medical chart to obtain your previous medical history.  Information about your 
health history will be recorded in the study database.  Other information collected from your 
medical record will include: your height and weight, serum creatinine, blood type, Rh factor, HLA 
& PRA (tests related to your immune system’s compatibility for the kidney transplant), CBC, viral 
panel results (Hepatitis B, Hepatitis C, Human Immunodeficiency Virus (HIV), Cytomegalovirus 
(CMV), and Epstein–Barr virus (EBV), and immunosuppression medication levels.   
 
Blood Samples 
All transplant participants have blood drawn after their transplant.  You will have some extra blood 
drawn for this research study according to the schedule above.  In most cases, this blood can be 
collected when you are already having blood drawn for your clinic visit or a standard lab visit.  The 
research samples will be sent to the Principal Investigator’s (Dr. Lorenzo Gallon) research 
laboratory on Northwestern’s medical campus.  The amount of blood drawn for research purposes 
will not exceed 60 mL or 4 tablespoons of blood during a 6-week period.  
 


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Kidney Biopsy  
A kidney biopsy is a procedure to remove and examine a small piece of kidney tissue. At 
Northwestern, it is recommended that all recipients have this procedure performed on their 
transplanted kidneys, at time of transplant and then at 3, 12 and 24 months post-transplant, These 
biopsies will be billed to you or your insurance company. If you choose to participate in this study, 
an additional piece of tissue will be taken for research during each of your routine care biopsies.  
Only the extra tissue sample taken for this study is considered a research-related test.   
   
Urine Collection 
You will have urine collected at the time points listed in the schedule above. 
 
What are some of the risks and discomforts that may happen to people who are in this study?   
According to a report sent by Novartis Pharmaceuticals in March 2014, some participants receiving 
everolimus in other research studies have experienced cardiac arrest, with some instances resulting 
in death. Based on these findings, your risk of cardiac arrest, and death as a result, may be increased 
with the use of everolimus.  
 
In another report sent by Novartis Pharmaceuticals in May 2014, some participants in other research 
studies have experienced ascites which is a build-up of fluid in the abdomen causing bloating and 
discomfort. Based on these findings, your risk of ascites may be increased with the use of 
everolimus. 
 
Additionally, taking part in this study may involve the following risks: 
 
Blood Draws 
The risks of drawing blood are pain, bruising, infection, redness, swelling at the site of the needle 
entry, and a small chance of fainting.  Care will be taken to avoid these risks.  
 
Biopsies 
No biopsies will be performed solely due to your participation in this study.  However, at your 
routine care biopsies, an extra piece of kidney tissue (possibly requiring an extra needle) will be 
taken for use in this study.  Risks of a kidney biopsy include bleeding in or around the kidney that 
can lead to a fall in blood pressure and rise in heart rate.  In some cases a hole can form between 
blood vessels inside the kidney.  The hole is called a fistula.  Most fistulas close on their own and 
do not present a problem.  However, occasionally (in approximately 1 in 100 cases), a hole in a 
blood vessel can lead to bleeding, and may require a blood transfusion.  Very rarely (in less than 1 
in 1000 cases), the fistula can lead to a need for surgery or result in loss of the kidney.  Additional 
risks of a biopsy include;infection, pain, bleeding at the site of needle entry and/or having blood in 
urine.  There is a very small chance a small scar may form at the site of needle entry.  To lessen 
these risks, the biopsy procedure will be done using ultrasound guidance.  Ultrasound allows the 
doctor to see where to place the needle.  
 
These risks for a kidney biopsy will be explained to you by your doctor.  The risks of the kidney 
biopsy are not changed because you are in this study.  However, an extra needle is sometimes 
required to get the research tissue for the study, and may minimally increase the risks associated 
with this procedure.   
 
Genetic Information 


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Genetic testing will be performed on your blood samples for this study. Knowledge of these tests 
may make you feel emotionally uncomfortable. This genetic information is collected to see how 
your genes related to your immune system have responded to your immunosuppression 
medications. These tests are only for research. That means the results will not be shared with you, 
even if they containextra information about conditions you may have, or about certain types of 
treatments that may help you.  
 
If you withdraw from the study your samples from these tests will be destroyed.  Strict 
precautionary measures will be taken to ensure that this genetic information and any identifying 
information are only accessible to the appropriate research staff.  We will password-protect the 
electronic documents containing genetic information, and keep all files with genetic information in 
locked areas to which only authorized staff have access. 
 
What do I need to know about reproductive health/sexual activity if I am in this study? 
The drugs associated with this study may be harmful to a fetus.  Sexually active men and women 
should use an effective method of birth control while taking the anti-rejection drugs. Condoms or 
diaphragm with spermicide, intrauterine devices (IUD), hormonal pills, injections, or patches, 
surgical sterilization (vasectomy or tubal ligation) and complete abstinence are examples of 
effective methods of birth control. Only methods that use condoms provide adequate protection 
against sexually transmitted diseases. 
 
If you or your partner becomes pregnant while on the study, you must inform your study 
nurse/physician immediately.  You may be required to switch anti-rejection drugs, in which case 
other treatment options will be discussed with you. Information will be collected on your pregnancy 
and the outcome. 
 
What are some of the benefits that are likely to come from my being in this study? 
If you take part in this study there may be no direct medical benefit to you.  The information learned 
from this study may someday benefit future kidney transplant recipients.   
 
What other procedures or courses of treatment might be available to me? 
You do not have to take part in this research study. Before you decide to take part in this study, you 
can speak with the Principal Investigator Dr. Lorenzo Gallon about these and other options 
available to you. Your decision to take part in this study will not affect your chances of receiving a 
kidney transplant or the amount of time you will wait for a transplant.  The drugs used in this study 
are FDA approved and are available outside of this study. 
 
Your study doctor will tell you about any new information (good or bad) from this research or other 
studies that relate to this study.  If new information is provided to you, you may be asked to re-
consent to continue your participation. 
 
Are there any financial costs to being in this study? 
While there will be tests and procedures done only for this study, there will be no additional costs to 
you for being in this study.    
 
You will be responsible for the cost of your transportation, including parking. You will receive a 
voucher for up to 6 hours of free parking for your study visits. This voucher is only valid if you park 
in the 251 E. Huron Street Garage, which is connected to the Galter Pavilion and the Feinberg 
Pavilion (hospital) by the street overpass on the second floor. The garage is also known as 
“university parking garage A.”  If you park in any other garage, this parking voucher will not be 


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valid and you will need to pay for your own parking. 
 
What should I do if I am injured as a result of being in this study?  
If you have an injury or illness from taking the study drug or procedures required for this study, the 
reasonable medical expenses required to treat such injury or illness may be paid for by the study 
sponsor.    
  
The coverage for such injury or illness is only available if the Northwestern University principal 
investigator has decided that the injury/illness is directly related to the study drug or study 
procedures and is not the result of a pre-existing condition or the normal progression of your 
disease, or because you have not followed the directions of the study doctor. If your insurance is 
billed, you may be required to pay deductibles and co-payments that apply.  You should check with 
your insurance company about any such payments. 
 
If I have questions or concerns about this research study, whom can I call? 
You can call us with your questions or concerns. If you have any illness or injury during your time 
on this study, you should call us promptly. Lorenzo Gallon, MD is the person in charge of this 
research study. You can call him at telephone number 312-695-4457, Monday through Friday, from 
9am to 5pm. 
 
For problems arising evenings or weekends, you may call 312-695-8900 and ask to speak to the 
transplant research nurse on-call.  
 
Reasons why you may be taken off study without your consent: 
You may be removed from the study without your consent at any time for the following reasons: 
        
- Your doctor or the study staff thinks that it is in your best interest not to continue in the            
study         
- You are unable to complete required study visits 
- The study is stopped by Northwestern University, or Novartis Pharmaceuticals 
 
If you are discontinued from the study, the study staff will contact you to discuss the procedures and 
appropriate future treatment for your continued care.  
 
What are my rights as a research subject? 
If you choose to be in this study, you have the right to be treated with respect, including respect for 
your decision whether or not you wish to continue or stop being in the study.  You are free to 
choose to stop being in the study at any time.   
 
Choosing not to be in this study or to stop being in this study will not result in any penalty to you or 
loss of benefit to which you are entitled.  Your choice not to be in this study will not negatively 
affect the routine medical care to which you are otherwise entitled.  
 
If you want to speak with someone who is not directly involved in this research, or have questions 
about your rights as a research subject, please contact the Northwestern University Institutional 
Review Board (IRB) Office.  You can call them at 312-503-9338. 
 
What about my confidentiality and privacy rights?  
¨ We are committed to respect your privacy and to keep your personal information confidential.  
When choosing to take part in this study, you are giving us the permission to use your personal 


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health information that includes health information in your medical records and information 
that can identify you. For example, personal health information may include your name, 
address, phone number or social security number. Your health information we may collect and 
use for this research includes:  
¨ Transplant history: Date of transplant, cause of renal disease 
¨ Demographics: Age, race, ethnicity, gender 
¨ Results of physical examinations 
¨ Medical history  
¨ Blood test results 
¨ All medications 
¨ Related events of interest: admissions to the hospital, rejection, infections, etc. 
 
During this study you may be coming to the Northwestern Memorial Hospital clinical offices for 
research appointments or to get clinical services, such as lab tests, needed for the study.  When that 
happens, you will be scheduled for these services through the NMH computer system.  When a 
clinical exam or lab is done by NMH or one of its employees for the purpose of this research study, 
that information will be kept in both NMH’s clinical records and in the study records. 
 
The following groups of people may give the researchers information about you: All current and 
previous health care providers, including but not limited to Northwestern Medical Group (NMG) 
and Northwestern Memorial Hospital (NMH). 
Your medical and research records will be confidential to the extent permitted by law. Data from 
this study will be entered into a computerized database through a secured website and only study 
staff with a password will be allowed to enter data.  Efforts will be made to keep your personal 
information private; however, we cannot guarantee complete confidentiality.  Your data will be 
identified by a code and not by your name. Personal information from your records will not be 
released without your written permission.   
Once we have the health information listed above, we may share some of this information with the 
following people. Please note that any research information shared with people outside of 
Northwestern University and its clinical partners (or affiliates), the Northwestern University 
Institutional Review Board Office and Office for Research Integrity, the US Office of Research 
Integrity, the US Office for Human Research Protections, the US Food and Drug Administration 
will not contain your name, address, telephone or social security number or any other direct 
personal identifier unless disclosure of the direct identifier is necessary for review by such parties or 
is required by law [except that such information may be viewed by the Study sponsor and its 
partners or contractors at the Principal Investigators office]. 
• Authorized members of the Northwestern University workforce, who may need to see your 
information, such as administrative staff members from the Office for Research, Office for 
Research Integrity and members of the Institutional Review Board (a committee which is 
responsible for the ethical oversight of the study). 
• Clinical affiliates, including but not limited the Rehabilitation Institute of Chicago (RIC), 
Northwestern Medical Group (NMG), Northwestern Memorial Hospital (NMH), 
Northwestern Lake Forest Hospital (NLFH), and the Ann & Robert H. Lurie Children’s 
Hospital of Chicago (Lurie Children’s).  Your participation in this study may be tracked in 
an electronic database and may be seen by investigators running other trials that you are 
enrolled in and by your healthcare providers. 


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• Clinical affiliates, including but not limited to Northwestern Medical Group (NMG), 
Northwestern Memorial Hospital (NMH), and Northwestern Lake Forest Hospital (NLFH), 
for purposes including, but not limited to, the affiliate’s provision of care to you and/or the 
affiliate’s scheduling of appointments and/or billing activities. 
• Other University research centers and University contractors who are also working on the 
study, 
• Study monitors and auditors who make sure that the study is being done properly,  
• Novartis Pharmaceuticals, who is sponsoring the study, and that company’s contractors and 
partners. 
• Government agencies and public health authorities, such as the Food and Drug 
Administration (FDA) and the Department of Health and Human Services (DHHS). 
 
Those persons who get your health information may not be required by Federal privacy laws (such 
as the Privacy Rule) to protect it. Some of those persons may be able to share your information with 
others without your separate permission. 
The results of this study may also be used for teaching, publications, or for presentation at scientific 
meetings. If your individual results are discussed, your identity will be protected by using a study 
code number rather than your name or other identifying information.  Examples of identifying 
information include medical record number, Social Security number, and address. 
 
ClinicalTrials.gov  
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by 
U.S. Law. This Web site will not include information that can identify you. At most, the Web site 
will include a summary of the results. You can search this Web site at any time.   
 
Please note that: 
Ø You do not have to sign this consent form.  If you do not, it will not affect your treatment by 
health care providers, or the payment or enrollment in any health plans, or affect your 
eligibility for benefits. However, you will not be allowed to take part in this research study.  
Ø You may change your mind and “take back” (revoke) this consent at any time. Even if you 
revoke this consent, the Principal Investigator may still use or share health information that 
was obtained about you before you revoked your consent as needed for the purpose of this 
study. To revoke your consent for the use of your health information, you must do so in 
writing to:                            
 
Lorenzo Gallon, MD 
Northwestern University 
Transplant Surgery- Clinical Research 
676 N. St. Clair Street, Ste. 1900 
Chicago IL, 60611 
 
Ø Unless you revoke your consent, it will not expire. If you “take back” (revoke) your consent 
to use any blood or tissue taken for the study, the Principal Investigator will make sure that 
these specimens are destroyed or will make sure that all information that could identify you 
is removed from these samples. 
 
 
 


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Consent Summary:  
I have read this consent form and the research study has been explained to me. I have been given 
time to ask questions, and have been told whom to contact if I have more questions.  I agree to be in 
the research study described above.  
 
A copy of this consent form will be provided to me after I sign it. A copy of this signed consent 
document, information about this study and the results of any test or procedure done may be 
included in my medical record and may be seen by my insurance company.  
 
 
_______________________________________________________ 
 
__________ 
Subject’s Name (printed) and Signature 
 
 
 
 
 
Date 
 
_______________________________________________________ 
 
__________ 
Name (printed) and Signature of Person Obtaining Consent  
 
 
Date