Transplant RejectionFACTORNCT01338779
Study of Tolerant Kidney Transplant Recipients
An observational study of Transplant Rejection and Kidney Transplantation, run by National Institute of Allergy and Infectious Diseases (NIAID) at 4 sites in United States.
Trial summary
The purpose of this multi-center (observational) registry study is to establish a database of clinical and laboratory information that may help to identify any unique characteristics of tolerant participants that differ from participants who reject their kidney after discontinuing immunosuppressive drugs. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Transplant Rejection, Kidney Transplantation, Renal Transplantation
- How many people
- 197 participants
- Where
- 4 sitesUnited States
- Study dates
- May 2004to Aug 2015
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: * Primary Care Clinics * Major Kidney (Renal) Transplant Programs
Who may be able to join
- Must be a renal transplant recipient or living donor
- Meet the criteria for inclusion in one of the study enrollment groups
- Provide informed consent
Who cannot join
- AIDS [includes all HIV-infected persons who have less than 200 cells/mm(3) CD4+ T-lymphocytes/microL, or a CD4+ T-lymphocyte/micro liter or a CD4+ T-lymphocyte percent of total lymphocytes less than 14, or who have been diagnosed with an AIDS-defining condition as defined by the Centers for Disease Control and Prevention (CDC)
- Current malignancy requiring recent surgery, ongoing chemotherapy or radiation
- Acute systemic infections within 30 days prior to enrollment
- Pregnancy
- Transplant of another organ
- Note: Patients meeting any of the exclusion criteria, if identified to have been clinically tolerant prior to the occurrence of the excluding condition, will be enrolled and demographic data collected for the registry; however, the decision as to whether or not to collect blood, urine, and tissue samples will be deferred until the participant's condition improves and the clinically tolerant state persists.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Emory University
Atlanta, Georgia, 30322
NIH Clinical Center
Bethesda, Maryland, 20814
University of Wisconsin
Madison, Wisconsin, 53792
Swedish Medical Center
Seattle, Washington, 98104
About this study
Official title: Identification and Mechanistic Investigations of Tolerant Transplant Recipients
The purpose of this multi-center (observational) registry study is to establish a database of clinical and laboratory information that may help to identify any unique characteristics of tolerant participants that differ from participants who reject their kidney after discontinuing immunosuppressive drugs.
Read the detailed description
Following kidney (renal) transplantation, one possible complication is rejection of the new kidney. This occurs as a results of the body's immune system attacking (or rejecting) the newly transplanted kidney. After transplant, medicines known as "immunosuppressive" or "anti-rejection" drugs are given to transplant recipients to help prevent rejection of the transplanted kidney. If a transplant recipient stops taking these medicines, they almost always reject their transplanted kidney. However, in some exceptionally rare instances, transplant recipients who stop taking these drugs do not reject their kidney, and the kidney keeps working. The recipients are said at that point to "tolerate" the transplanted kidney, and this condition is referred to as "tolerance".
In this study, participants will be asked to provide consent for the collection of extensive demographic and clinical information; medical histories; and blood and urine samples. Blood and urine samples collected will be used to perform specific assays to help define mechanisms of tolerance.
Originally the study included 11 groups as listed; however, at present only groups 1,4, and 8 remain active. Whereas the initial study duration was 6 years, this was extended to 11 years in order to follow over more extended time a B cell signature identified for tolerant kidney subjects and how this signature may change. (Refer to publications section: Newell, Kirk et al, J Clin Invest. 2010).
- Conditions
- Transplant Rejection, Kidney Transplantation, Renal Transplantation, Renal Transplant, Transplant Tolerance
- Keywords
- Tolerance, Renal, Allograft, B Cell Signature
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 - kidney tolerant | Renal allograft recipients showing functional tolerance (normal and stable renal function) after discontinuation of immunosuppressive medications for at least 1 year (or based on the investigator's discretion). | |
| Group 2 - acceptor | Enrollment for group 2 was closed. Renal transplant recipients with functioning allografts (not on dialysis) who had not received immunosuppressive medications for at least 1 year (or at investigator's discretion) but who had moderately impaired or gradually deteriorating renal function, defined as creatinine clearance (CrCl) < 40 mL/min and/or creatinine > 50% above baseline value, and thus did not qualify for group 1. | |
| Group 3 - kidney graft loss | Enrollment for group 3 is closed. These were renal transplant recipients who had subsequently rejected and lost function of their transplanted kidney. | |
| Group 4 - kidney monotherapy | Renal transplant recipients showing stable and normal renal function after receiving only prednisone 10 mg/day for at least 1 year (or based on the investigator's discretion). | |
| Group 5 - kidney standard immunotherapy | Enrollment for group 5 is closed. Stable renal transplant recipients currently on standard immunosuppression. | |
| Group 6 - kidney chronic rejector | Enrollment for group 6 is closed. Chronic allograft nephropathy group. | |
| Group 7 - kidney identical twin | Enrollment for group 7 is closed. | |
| Group 8 - living kidney donors | Corresponding to recipients in group 1 or 4. | |
| Group 9 - healthy controls | Enrollment for group 9 is closed. | |
| Group 10 - liver tolerant | Enrollment for group 10 is closed. Liver allograft recipients with functional tolerance (stable and normal liver function) after cessation of immunosuppressive medications for at least three years (or at investigator's discretion). | |
| Group 11 - liver standard immunotherapy | Enrollment for group 11 is closed. Subjects with a liver transplant who never had an attempt made to discontinue gradually their immunosuppression and who are currently taking standard immunosuppressive medications and have stable and normal liver allograft function after at least 1 year of receiving these drugs. |
What is being measured
The primary outcome is the main question the study is designed to answer.
To identify individuals who have received a kidney transplant and who have achieved a state of immune tolerance to graft
Measured: 0 to 11 years
To create an electronic registry of data on the tolerant and comparison groups that will serve as the basis for statistical analyses
Measured: 0 to 11 years
To use data from the registry to perform classical tests of hypotheses regarding the establishment of immune tolerance
Measured: 0 to 11 years
To use data from the registry to create and assess predictive statistical models to model such variables as clinical features, duration of tolerant state, and time to onset of immune sensitization
Measured: 0 to 11 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2011 (estimated)
- Study startMay 2004
- Primary completionAug 2015
- Study completionAug 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Transplant RejectionStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 197 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Immune Tolerance Network (ITN)
- Responsible party
- Sponsor
- Investigators
- Kenneth Newell, MD, PhD, Study chair, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01338779
- Sponsor's protocol ID
- DAIT ITN507ST
- Acronym
- FACTOR
- Status last verified
- Sep 2016
- First submitted
- 18 Apr 2011
- Last updated
- 30 Sep 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Participant level data access is available to the public in: 1.) the Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts; and 2.) TrialShare, the Immune Tolerance Network (ITN) Clinical Trials Research Portal.
Publications
Schroppel B, Heeger PS. Gazing into a crystal ball to predict kidney transplant outcome. J Clin Invest. 2010 Jun;120(6):1803-6. doi: 10.1172/JCI43286. Epub 2010 May 24.
PubMed 20501950Newell KA, Asare A, Kirk AD, Gisler TD, Bourcier K, Suthanthiran M, Burlingham WJ, Marks WH, Sanz I, Lechler RI, Hernandez-Fuentes MP, Turka LA, Seyfert-Margolis VL; Immune Tolerance Network ST507 Study Group. Identification of a B cell signature associated with renal transplant tolerance in humans. J Clin Invest. 2010 Jun;120(6):1836-47. doi: 10.1172/JCI39933. Epub 2010 May 24.
PubMed 20501946Haynes LD, Jankowska-Gan E, Sheka A, Keller MR, Hernandez-Fuentes MP, Lechler RI, Seyfert-Margolis V, Turka LA, Newell KA, Burlingham WJ. Donor-specific indirect pathway analysis reveals a B-cell-independent signature which reflects outcomes in kidney transplant recipients. Am J Transplant. 2012 Mar;12(3):640-8. doi: 10.1111/j.1600-6143.2011.03869.x. Epub 2011 Dec 7.
PubMed 22151236Newell KA, Asare A, Sanz I, Wei C, Rosenberg A, Gao Z, Kanaparthi S, Asare S, Lim N, Stahly M, Howell M, Knechtle S, Kirk A, Marks WH, Kawai T, Spitzer T, Tolkoff-Rubin N, Sykes M, Sachs DH, Cosimi AB, Burlingham WJ, Phippard D, Turka LA. Longitudinal studies of a B cell-derived signature of tolerance in renal transplant recipients. Am J Transplant. 2015 Nov;15(11):2908-20. doi: 10.1111/ajt.13480. Epub 2015 Oct 13.
PubMed 26461968Yu J, Steck AK, Babu S, Yu L, Miao D, McFann K, Hutton J, Eisenbarth GS, Klingensmith G. Single nucleotide transcription factor 7-like 2 (TCF7L2) gene polymorphisms in antiislet autoantibody-negative patients at onset of diabetes. J Clin Endocrinol Metab. 2009 Feb;94(2):504-10. doi: 10.1210/jc.2007-2694. Epub 2008 Dec 2.
PubMed 19050058Brennan DC, Shannon MB, Koch MJ, Polonsky KS, Desai N, Shapiro J. Portal vein thrombosis complicating islet transplantation in a recipient with the Factor V Leiden mutation. Transplantation. 2004 Jul 15;78(1):172-3. doi: 10.1097/01.tp.0000128332.71657.ea. No abstract available.
PubMed 15257060
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Identification and Mechanistic Investigations of Tolerant Transplant Recipients
- ClinicalTrials.gov ID
- NCT01338779
- Acronym / sponsor ID
- FACTOR / DAIT ITN507ST
- Conditions
- Transplant Rejection, Kidney Transplantation, Renal Transplantation, Renal Transplant, Transplant Tolerance
- Keywords
- Tolerance, Renal, Allograft, B Cell Signature
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 197 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Immune Tolerance Network (ITN)
- Study start
- May 2004
- Primary completion
- Aug 2015 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 20 Apr 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this multi-center (observational) registry study is to establish a database of clinical and laboratory information that may help to identify any unique characteristics of tolerant participants that differ from participants who reject their kidney after discontinuing immunosuppressive drugs.
Detailed description
Following kidney (renal) transplantation, one possible complication is rejection of the new kidney. This occurs as a results of the body's immune system attacking (or rejecting) the newly transplanted kidney. After transplant, medicines known as "immunosuppressive" or "anti-rejection" drugs are given to transplant recipients to help prevent rejection of the transplanted kidney. If a transplant recipient stops taking these medicines, they almost always reject their transplanted kidney. However, in some exceptionally rare instances, transplant recipients who stop taking these drugs do not reject their kidney, and the kidney keeps working. The recipients are said at that point to "tolerate" the transplanted kidney, and this condition is referred to as "tolerance".
In this study, participants will be asked to provide consent for the collection of extensive demographic and clinical information; medical histories; and blood and urine samples. Blood and urine samples collected will be used to perform specific assays to help define mechanisms of tolerance.
Originally the study included 11 groups as listed; however, at present only groups 1,4, and 8 remain active. Whereas the initial study duration was 6 years, this was extended to 11 years in order to follow over more extended time a B cell signature identified for tolerant kidney subjects and how this signature may change. (Refer to publications section: Newell, Kirk et al, J Clin Invest. 2010).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 11
| Arm | Type | Receives |
|---|---|---|
| Group 1 - kidney tolerant | – | –Renal allograft recipients showing functional tolerance (normal and stable renal function) after discontinuation of immunosuppressive medications for at least 1 year (or based on the investigator's discretion). |
| Group 2 - acceptor | – | –Enrollment for group 2 was closed. Renal transplant recipients with functioning allografts (not on dialysis) who had not received immunosuppressive medications for at least 1 year (or at investigator's discretion) but who had moderately impaired or gradually deteriorating renal function, defined as creatinine clearance (CrCl) < 40 mL/min and/or creatinine > 50% above baseline value, and thus did not qualify for group 1. |
| Group 3 - kidney graft loss | – | –Enrollment for group 3 is closed. These were renal transplant recipients who had subsequently rejected and lost function of their transplanted kidney. |
| Group 4 - kidney monotherapy | – | –Renal transplant recipients showing stable and normal renal function after receiving only prednisone 10 mg/day for at least 1 year (or based on the investigator's discretion). |
| Group 5 - kidney standard immunotherapy | – | –Enrollment for group 5 is closed. Stable renal transplant recipients currently on standard immunosuppression. |
| Group 6 - kidney chronic rejector | – | –Enrollment for group 6 is closed. Chronic allograft nephropathy group. |
| Group 7 - kidney identical twin | – | –Enrollment for group 7 is closed. |
| Group 8 - living kidney donors | – | –Corresponding to recipients in group 1 or 4. |
| Group 9 - healthy controls | – | –Enrollment for group 9 is closed. |
| Group 10 - liver tolerant | – | –Enrollment for group 10 is closed. Liver allograft recipients with functional tolerance (stable and normal liver function) after cessation of immunosuppressive medications for at least three years (or at investigator's discretion). |
| Group 11 - liver standard immunotherapy | – | –Enrollment for group 11 is closed. Subjects with a liver transplant who never had an attempt made to discontinue gradually their immunosuppression and who are currently taking standard immunosuppressive medications and have stable and normal liver allograft function after at least 1 year of receiving these drugs. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- * Primary Care Clinics * Major Kidney (Renal) Transplant Programs
Key inclusion criteria (3 listed)
- Must be a renal transplant recipient or living donor
- Meet the criteria for inclusion in one of the study enrollment groups
- Provide informed consent
Key exclusion criteria (6 listed)
- AIDS [includes all HIV-infected persons who have less than 200 cells/mm(3) CD4+ T-lymphocytes/microL, or a CD4+ T-lymphocyte/micro liter or a CD4+ T-lymphocyte percent of total lymphocytes less than 14, or who have been diagnosed with an AIDS-defining condition as defined by the Centers for Disease Control and Prevention (CDC)
- Current malignancy requiring recent surgery, ongoing chemotherapy or radiation
- Acute systemic infections within 30 days prior to enrollment
- Pregnancy
- Transplant of another organ
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
To identify individuals who have received a kidney transplant and who have achieved a state of immune tolerance to graft
Time frame: 0 to 11 years
To create an electronic registry of data on the tolerant and comparison groups that will serve as the basis for statistical analyses
Time frame: 0 to 11 years
To use data from the registry to perform classical tests of hypotheses regarding the establishment of immune tolerance
Time frame: 0 to 11 years
To use data from the registry to create and assess predictive statistical models to model such variables as clinical features, duration of tolerant state, and time to onset of immune sensitization
Time frame: 0 to 11 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2016.
- Background: PubMed 20501950Schroppel B, Heeger PS. Gazing into a crystal ball to predict kidney transplant outcome. J Clin Invest. 2010 Jun;120(6):1803-6. doi: 10.1172/JCI43286. Epub 2010 May 24.
- Results publication: PubMed 20501946Newell KA, Asare A, Kirk AD, Gisler TD, Bourcier K, Suthanthiran M, Burlingham WJ, Marks WH, Sanz I, Lechler RI, Hernandez-Fuentes MP, Turka LA, Seyfert-Margolis VL; Immune Tolerance Network ST507 Study Group. Identification of a B cell signature associated with renal transplant tolerance in humans. J Clin Invest. 2010 Jun;120(6):1836-47. doi: 10.1172/JCI39933. Epub 2010 May 24.
- Results publication: PubMed 22151236Haynes LD, Jankowska-Gan E, Sheka A, Keller MR, Hernandez-Fuentes MP, Lechler RI, Seyfert-Margolis V, Turka LA, Newell KA, Burlingham WJ. Donor-specific indirect pathway analysis reveals a B-cell-independent signature which reflects outcomes in kidney transplant recipients. Am J Transplant. 2012 Mar;12(3):640-8. doi: 10.1111/j.1600-6143.2011.03869.x. Epub 2011 Dec 7.
- Results publication: PubMed 26461968Newell KA, Asare A, Sanz I, Wei C, Rosenberg A, Gao Z, Kanaparthi S, Asare S, Lim N, Stahly M, Howell M, Knechtle S, Kirk A, Marks WH, Kawai T, Spitzer T, Tolkoff-Rubin N, Sykes M, Sachs DH, Cosimi AB, Burlingham WJ, Phippard D, Turka LA. Longitudinal studies of a B cell-derived signature of tolerance in renal transplant recipients. Am J Transplant. 2015 Nov;15(11):2908-20. doi: 10.1111/ajt.13480. Epub 2015 Oct 13.
- Results publication: PubMed 19050058Yu J, Steck AK, Babu S, Yu L, Miao D, McFann K, Hutton J, Eisenbarth GS, Klingensmith G. Single nucleotide transcription factor 7-like 2 (TCF7L2) gene polymorphisms in antiislet autoantibody-negative patients at onset of diabetes. J Clin Endocrinol Metab. 2009 Feb;94(2):504-10. doi: 10.1210/jc.2007-2694. Epub 2008 Dec 2.
- Results publication: PubMed 15257060Brennan DC, Shannon MB, Koch MJ, Polonsky KS, Desai N, Shapiro J. Portal vein thrombosis complicating islet transplantation in a recipient with the Factor V Leiden mutation. Transplantation. 2004 Jul 15;78(1):172-3. doi: 10.1097/01.tp.0000128332.71657.ea. No abstract available.
- National Institute of Allergy and Infectious Diseases (NIAID)Link provided by the sponsor.
- Immune Tolerance Network (ITN)Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Participant level data access is available to the public in: 1.) the Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts; and 2.) TrialShare, the Immune Tolerance Network (ITN) Clinical Trials Research Portal.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kenneth Newell, MD, PhD study chair
Emory University
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Transplant Rejection and Kidney Transplantation, run by National Institute of Allergy and Infectious Diseases (NIAID) at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To identify individuals who have received a kidney transplant and who have achieved a state of immune tolerance to graft (time frame: 0 to 11 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01338779, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2016.