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Sponsored by: |
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) |
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Information provided by: | National Institutes of Health Clinical Center (CC) |
ClinicalTrials.gov Identifier: | NCT00076570 |
This study will test the safety and effectiveness of a combination of three drugs followed by long-term treatment with just one drug in preventing organ rejection in kidney transplant patients. Current anti-rejection medicines are not completely effective in preventing rejection. This trial will test how well Thymoglobulin, Tacrolimus, and Sirolimus work together post-transplant and if the treatment can be reduced over time to control rejection with either Tacrolimus or Sirolimus alone.
Candidates for kidney transplantation at the National Institutes of Health Clinical Center may participate in this 5-year study. Patients will be screened for eligibility with a medical history, physical examination, and blood tests.
Participants will undergo the following tests and procedures:
Condition | Intervention | Phase |
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Kidney Transplantation |
Drug: Rabbit anti-thymocyte globulin |
Phase II |
Study Type: | Interventional |
Study Design: | Treatment |
Official Title: | Depletional Induction With Rabbit Anti-Thymocyte Globulin, Followed by Two Approaches Toward Monotherapy Immunosuppression in Kidney Transplant Recipients |
Estimated Enrollment: | 60 |
Study Start Date: | January 2004 |
This protocol will test a novel combination of three FDA-approved immunosuppressive agents for its ability to prevent human renal allograft rejection, and eventually allow for a single agent to be used for chronic maintenance immunosuppression. It will test two variations of the therapy to determine if one is better tolerated or superior for the prevention of rejection.. It will also evaluate the two variations for their ability to induce donor-specific hyporesponsiveness over time. All patients will receive rabbit anti-thymocyte globulin (RATG, Thymoglobulin, Genzyme Corporation) for four consecutive days beginning within 24 hours prior to allograft reperfusion to achieve perioperative T-cell depletion. Glucocorticosteroids will be given as premedication for the RATG treatment to limit the cytokine release syndrome associated with this antibody preparation. However, thereafter, steroids will not be used for immunosuppression. Beginning on the first post-operative day all patients will be started on oral therapy with sirolimus (Rapamune, Wyeth), and tacrolimus (Prograf, Fujisawa). These two agents have been shown to synergistically inhibit allograft rejection. Patients will remain on these agents for 6 months. After 6 months, patients who have been rejection-free will undergo a protocol surveillance biopsy and then be weaned from either sirolimus or tacrolimus in a randomized fashion. Patients will be followed to determine if this monotherapy approach prevents rejection, and if either agent is significantly more efficacious in inducing a state of donor-specific hyporesponsiveness. A follow-up biopsy will be performed on each patient 1 year after he or she has been weaned to monotherapy immunosuppression.
A total of sixty non-sensitized (peak Panel Reactive Antibody less than 20 percent, non-HLA identical recipients of first living donor or cadaveric kidney allografts will be enrolled and followed for five years. In addition to standard measures of allograft and patient survival, assays will be performed to evaluate potential mechanisms of donor-specific hyporesponsiveness.
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Candidates for a kidney transplant at the Clinical Center.
Willingness and legal ability to give informed consent.
Availability of donor tissue for testing. This could include splenic or peripheral blood lymphocytes from a cadaveric donor or a willing living donor who consents to periodic phlebotomy for peripheral blood lymphocyte isolation.
EXCLUSION CRITERIA:
Immunosuppressive drug therapy at the time of or 2 months prior to enrollment. Specifically, candidates may not be taking prednisone, cyclosporine, tacrolimus, azathioprine, mycophenolate mofetil, anti-lymphocyte agents, cyclophosphamide, methotrexate, or other agents whose therapeutic effect is immunosuppressive.
Any active malignancy or any history of any hematogenous malignancy or lymphoma. Patients with primary, cutaneous basal cell or squamous cell cancers may be enrolled providing the lesions are appropriately treated prior to transplant.
Any known immunodeficiency syndrome, or other condition that, in the opinion of the investigators, would likely increase the risk of protocol participation or confound the interpretation of the data.
Any history of sensitization to rabbits or extensive exposure to rabbits, as defined by symptomatic allergic response upon exposure to rabbits.
Inability or unwillingness to comply with protocol monitoring and therapy including, among others, a history of noncompliance, circumstances where compliance with protocol requirements is not feasible due to living conditions, travel restrictions, access to urgent medical services, or access to anti-rejection drugs after the research protocol is completed.
Peak Panel Reactive Antibody greater than 20%, or historically positive crossmatch due to HLA-specific antibodies.
HLA identity between the donor and recipient.
Pregnancy or unwillingness to practice an approved method of birth control. Acceptable methods of birth control may include barrier methods (condom and/or diaphragm with spermicide), oral contraceptives, Norplant, Depo-Provera or partner sterility.
Responsible Party: | National Institutes of Health ( Monique E. Cho, M.D./National Institute of Diabetes and Digestive and Kidney Diseases ) |
Study ID Numbers: | 040099, 04-DK-0099 |
Study First Received: | January 26, 2004 |
Last Updated: | October 11, 2008 |
ClinicalTrials.gov Identifier: | NCT00076570 |
Health Authority: | United States: Federal Government |
Tolerance Kidney Transplant Polyclonal |
Antibody Kidney Kidney Transplant |
Antilymphocyte Serum Antibodies Immunoglobulins |
Immunologic Factors Physiological Effects of Drugs Immunosuppressive Agents Pharmacologic Actions |