Study of Tolerant Kidney Transplant Patients - Full Text View

Sponsors and Collaborators:	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Allergy and Infectious Diseases
Information provided by:	National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:	NCT00083655

Purpose

This study will investigate tolerance in kidney transplant patients. One of the most common complications of kidney transplantation is organ rejection, which occurs because the body's immune system tries to attack (reject) the newly transplanted kidney. To prevent this, patients are given immunosuppressive, or anti-rejection, drugs.

Most patients who stop taking these drugs reject their transplanted kidney; however, some patients do not reject the transplanted kidney and it continues to work well. These patients are said to "tolerate" the transplanted kidney, and this condition is referred to as tolerance. This study will establish a database of clinical and laboratory information that may help to identify unique characteristics of tolerant patients.

Patients 18 years of age and older who have had a kidney transplant and people who donated their kidneys for these patients may be eligible for this study. Patients are divided into 6 groups, according to the medicines they are currently taking and the status of their kidney function. A seventh group comprises patients who received a kidney from an identical twin, and an eighth group comprises kidney donors. Patients are screened with a medical history and a skin test to determine how well their immune system responds to foreign substances.

Patients in group 1 (patients who have stopped taking immunosuppressive medications for at least 1 year and whose transplanted kidney functions in a normal and stable manner) are required only to undergo the screening assessment, but may choose to participate in the following procedures, which are required for groups 2-7:

Baseline visit - Review of medical history and demographic information; routine blood tests; 24-hour urine sample; blood draw by standard method (phlebotomy) or by leukapheresis for tolerance tests. For leukapheresis, a needle is placed in a vein in each arm. Blood is collected from one arm and directed to a machine that separates it into its components. Some of the white blood cells are removed, and the rest of the blood is returned to the patient through the needle in the other arm.
Visits 1-6 (months 6, 12, 18, 24, and 36) - Review of medical history, including status of transplanted kidney; blood and urine samples for routine laboratory tests. If kidney function declines during the course of the study, patients will be asked to provide: additional blood and urine samples for routine laboratory tests; a 24-hour urine sample; and blood for tolerance tests, collected by standard phlebotomy or leukapheresis.

Patients in all groups may be asked to provide a biopsy sample of their transplanted kidney for tolerance assays and for microscopic examination. The biopsy may be repeated if kidney function worsens. For this procedure, a small piece of the transplanted kidney is removed with a special needle. Biopsies are an optional procedure.

Kidney donors provide blood samples for tolerance assays. They may be asked to provide additional samples if the kidney they donated deteriorates in function. The donor may choose to provide the blood sample by leukapheresis or by phlebotomy.

Condition
Immune System Diseases Graft Rejection Kidney Transplantation

Study Type:	Observational
Official Title:	Identification and Mechanistic Investigations of Tolerant Kidney Transplant Patients

Resource links provided by NLM:

MedlinePlus related topics: Kidney Transplantation

U.S. FDA Resources

Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment:	420
Study Start Date:	May 2004
Primary Completion Date:	July 2008 (Final data collection date for primary outcome measure)

Detailed Description:

This study is designed to obtain information from Kidney Transplant recipients and donors that will help scientists understand those factors causing and preventing transplant rejection. Approximately 210 renal transplant recipients and donors will be recruited into the study. The recruitment period for this study will be for 3 years after the first participant is enrolled. Based on the Network Executive Committee (NEC) and Tolerance Assay Sub-Group's annual review of the recruitment status of the study, the recruitment period may be adjusted. Participants will be classified into one of eight study groups and, once the participant has been assigned to a particular group, they will remain in that group until the end of the trial, regardless of change of status during the course of the study.

Each participant will be asked to provide consent for the collection of extensive demographic/clinical information and medical histories, and blood, urine and tissue (biopsy) samples upon study entry and during the study depending on the study group. Blood, urine and tissue samples (when provided) will be used to perform specific assays, to help define mechanism(s) of tolerance. In addition, specimens collected may be archived for use in future research assays. Participants will be asked to provide permission before any specimens are utilized in future research not described within this protocol. Information will be obtained regarding the donor of the renal allograft from the recipient's medical records. Living donors may be informed of this study by the recipient of their organ. The donor of the renal allograft may then contact study personnel if they are interested in participating in the study. The donor participants will be asked to consent to joining the study and asked to provide medical histories and blood samples. Information and archived blood and/or tissue samples from cadaveric donors will be requested from the Organ Procurement Organization (OPO) or UNOS (United Network for Organ Sharing) based on the unique UNOS number assigned to the donated kidney.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

INCLUSION CRITERIA:

Participants for this study will be renal transplant recipients or living-related donors who are:

18 years of age or older
meet the criteria for inclusion in one of the study groups
provide informed consent
participants who agree to a biopsy must have a International Normalized Ratio (INR) (minimum value less than 1.6) completed and/or a bleeding time of less than 9 minutes, to ensure that their risk of bleeding is minimal or a normal platelet function assay (PFA).

EXCLUSION CRITERIA:

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 Center for Disease Control (CDC)
Current malignancy requiring recent surgery, ongoing chemotherapy or radiation
Acute systemic infections within 30 days prior to enrollment
pregnancy
Non-compliance with their treatment follow-up
Transplant of another organ

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00083655

Locations

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892

Sponsors and Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Allergy and Infectious Diseases

More Information

Additional Information:

NIH Clinical Center Detailed Web Page This link exits the ClinicalTrials.gov site

Publications:

Benfield MR, Herrin J, Feld L, Rose S, Stablein D, Tejani A. Safety of kidney biopsy in pediatric transplantation: a report of the Controlled Clinical Trials in Pediatric Transplantation Trial of Induction Therapy Study Group. Transplantation. 1999 Feb 27;67(4):544-7.

Hergesell O, Felten H, Andrassy K, Kuhn K, Ritz E. Safety of ultrasound-guided percutaneous renal biopsy-retrospective analysis of 1090 consecutive cases. Nephrol Dial Transplant. 1998 Apr;13(4):975-7.

Heeger PS, Greenspan NS, Kuhlenschmidt S, Dejelo C, Hricik DE, Schulak JA, Tary-Lehmann M. Pretransplant frequency of donor-specific, IFN-gamma-producing lymphocytes is a manifestation of immunologic memory and correlates with the risk of posttransplant rejection episodes. J Immunol. 1999 Aug 15;163(4):2267-75.

Study ID Numbers:	040193, 04-DK-0193
Study First Received:	May 27, 2004
Last Updated:	August 24, 2009
ClinicalTrials.gov Identifier:	NCT00083655 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):

Tolerance
Renal
Allograft

Rejection
Immunosuppression
Kidney Transplant

Additional relevant MeSH terms:

Immune System Diseases

ClinicalTrials.gov processed this record on September 03, 2009