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Evaluating the Use of Thymoglobulin, Sirolimus, and Donor Bone Marrow with Kidney Transplantation Patients Clinical Trials Info presented on Clinical Trials Search is not intended to be a substitute for certified medical advice, visits or professional assistance using a real physician. We are not physicians. Always consult your dr. about Evaluating the Use of Thymoglobulin, Sirolimus, and Donor Bone Marrow with Kidney Transplantation Patients conditions. Clinical Trials Search.org is a site dedicated to listing clinical research studies in human subjects. Evaluating the Use of Thymoglobulin, Sirolimus, and Donor Bone Marrow with Kidney Transplantation Patients Clinical research trials and Evaluating the Use of Thymoglobulin, Sirolimus, and Donor Bone Marrow with Kidney Transplantation Patients health trials happen in many of localities throughout the U.S.. A clinical trial or clinical study is a research project with human volunteer subjects. Clinical drug trials and pharmaceutical clinical trials typically measure the effectualness of new drugs. The function of the studies / projects is to resolve particular human medical questions. Clinical trials are a popular manner for mDs, government agencies, and private sector corporations to discover remedies for all varieties of circumstances, like Evaluating the Use of Thymoglobulin, Sirolimus, and Donor Bone Marrow with Kidney Transplantation Patients. Evaluating the Use of Thymoglobulin, Sirolimus, and Donor Bone Marrow with Kidney Transplantation Patients Clinical Trials and other clinical trials allow volunteers to obtain healthcare treatment options before they are available to the masses. Some times the participants undergo professional assistance for free of charge, and occasionally they are paid for their time. Sometimes there is a cost for a Evaluating the Use of Thymoglobulin, Sirolimus, and Donor Bone Marrow with Kidney Transplantation Patients clinical trial. Human subjects often get the best healthcare available for their Evaluating the Use of Thymoglobulin, Sirolimus, and Donor Bone Marrow with Kidney Transplantation Patients condition. Dangers are a reality, however, and may include additional or frequent mD visits, healthcare dangers (potentially life-jeopardising), and/or the treatment being ineffectual. Trials are federally governed with rigorous guidelines to protect clinical trials patients.
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Home > "E" Clinical Trials Conditions > Evaluating the Use of Thymoglobulin, Sirolimus, and Donor Bone Marrow with Kidney Transplantation Patients  Evaluating the Use of Thymoglobulin, Sirolimus, and Donor Bone Marrow with Kidney Transplantation Patients
Evaluating the Use of Thymoglobulin, Sirolimus, and Donor Bone Marrow with Kidney Transplantation Patients
For Condition: Kidney Transplantation
Status: Recruiting
Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) ,
Synopsis: Patients with renal failure need chronic dialysis or a kidney transplant to survive. Most kidney transplant patients must take medicines indefinitely to prevent their immune systems from rejecting the kidney. Long-term exposure to these anti-rejection medicines can damage the transplanted kidney. The purpose of this study is to determine whether giving patients cells from the donor's bone marrow will reduce or eliminate the need for long-term use of these anti-rejection drugs. In addition to the donor's bone marrow cells, patients will receive the drugs thymoglobulin and sirolimus. A total of 20 patients will participate in this five-year study.
Details: This protocol will evaluate the combination of Thymoglobulin (Sangstat), sirolimus and donor bone marrow infusion for its ability to induce a state of donor specific hematopoietic chimerism and immune hyporesponsiveness within the context of renal transplantation. Thymoglobulin (Sangstat), a FDA-approved polyclonal rabbit-IgG antithymocyte preparation, will be given for up to ten days at the time of transplantation to effect lymphocyte depletion. This will be combined with sirolimus (rapamycin, Wyeth-Ayerst), an oral immunosuppressant agent recently approved by the FDA. Sirolimus allows for antigen specific T cell activation but prevents T cell clonal expansion by interrupting IL-2 receptor beta-chain signal transduction. Donor bone marrow will be administered seven days following transplant. Patients demonstrating six months of rejection free graft survival will have their sirolimus withdrawn over three months beginning at the sixth month anniversary of the transplant. The rationale for this combination is to 1) eliminate existing alloreactive T cell clones that could initiate a rejection at the time of transplantation using the T cell depleting properties of Thymoglobulin; 2) to create a milieu conducive for the induction of graft specific activation induced cell death (AICD) in repopulating T cells in the periphery and in the thymus such that an allospecific T cell deficit is induced; and 3) to establish a state of mixed allogeneic chimerism with donor bone marrow to promote the maintenance of allospecific hyporesponsiveness. The desired effect of this therapy is to induce a state of allospecific tolerance allowing for rejection-free graft survival without the chronic need for immunosuppressants, and to do so using a regimen that avoids most of the chronic drug toxicities inherent in the use of calcineurin inhibitors and glucocorticosteroids. Twenty people will be evaluated in this pilot protocol. Approximately ten will receive living donor kidney allografts and the remaining patients will receive cadaveric kidney allografts. Patients will be treated with Thymoglobulin beginning prior to graft implantation and continuing for approximately ten days. Glucocorticosteroids will be given during the first Thymoglobulin treatment to limit monocyte activation and prevent the cytokine release syndrome associated with the initial administration of this antibody preparation. Patients will be given sirolimus orally beginning the day after transplantation and continuously thereafter. Donor bone marrow will be administered seven days following transplantation. Patients will then be monitored for evidence of allograft rejection using standard functional parameters and protocol allograft biopsies. In addition, patients will be followed for specific desired effects, including a transient state of donor hematopoietic mixed microchimerism and allospecific AICD. Both of these are expected to promote the development of allospecific graft tolerance. This will be accomplished by assaying peripheral blood and allograft biopsies for apoptosis and the peripheral blood for evidence of alloreactive T cell clone depletion and donor chimerism.
Eligibility:
Study Type: Interventional, Treatment, Safety/Efficacy
Minimum Age/Maximum Age: /
Genders: Both
Protocol Entry Criteria: INCLUSION CRITERIA: Candidates for a kidney transplant. Age 12 through 50 at the time of transplant for the first 10 patients transplanted. Age 12 through 75 for subsequent patients. Patients younger than age 12 are better served being transplanted in a center with more extensive pediatric medical and nephrology support. Patients less than 12 years of age are also at higher risk for post transplant lymphoproliferative disorder following transplant than adults and intensive induction immunosuppression increases the risk further. The use of aggressive induction imunosuppression in this population would be inappropriate. Patients over the age of 75 generally require less immunosuppression than younger patients. The use of aggressive induction immunosuppression in this population would be inappropriate. Willingness 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 enrolled on the Clinical Center Living Donor Protocol who consents to periodic phlebotomy for peripheral blood lymphocyte isolation. Availability of adequate donor bone marrow for infusion. 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, antilymphocyte agents, cyclophosphamide, methotrexate, or other agents whose therapeutic effect is immunosuppressive. Treatment with a nucleoside analogue chemotherapeutic agent (i.e. fludarabine phosphate, cladribine, or pentostatin) within 12 months of kidney transplant. Absolute lymphocyte count less than 1000/mm(3) prior to first dose of Thymogobulin. Any active malignancy or any history of a hematologic 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. Donor/recipient combinations in which there are 0 HLA mismatches or in which the donor is homozygous for a shared HLA haplotype. Related donor/recipient combinations with a one haplotype match. Serologic HLA typing to be conducted at the Walter Reed Army Medical Center Tissue Typing Laboratory. Sensitization as defined by historical or current PRA less than 20 percent in patients receiving their first kidney allograft. First kidney graft survival less than 3 years or positive T or B cell crossmatch in patients receiving second kidney allograft. Historical or current positive T cell cross match between donor and recipient. Significant coagulopathy or requirement for anticoagulation therapy that would contraindicate protocol allograft biopsies. Platelet count less than 75,000/mm(3) at the time of transplant. Any known immunodeficiency syndrome such as HIV, Chronic Granulomatous Disease, Severe Combined Immunodeficiency, DiGeorge Syndrome, etc. Presence of uncorrected cardiac insufficiency (either valvular or vascular) or major vascular disease. Subjects unwilling/unable to practice birth control if potentially fertile. Presence of active or chronic infection. Any condition that would likely increase the risk of protocol participation or confound data interpretation such as 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. CMV positive donor to CMV negative recipient. Any history of allergy or anaphalaxis to rabbit proteins.
Total Enrollment: 20
Location and Contact Information:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) *Recruiting*
Bethesda, Maryland, 20892
United States
Recruiting Patient and Public Liaison Office 1-800-411-1222
Additional Information:
Study ID Numbers: 030204; 03-DK-0204
Study Start Date: June 9, 2003
Record last reviewed: March 17, 2004
Additional information available at: clinicaltrials.gov
Clinicaltrials.gov Reference link: NCT00062712
Other Kidney Transplantation Studies:
1. An Evaluation of IV Gamma Globulin As a Method to Improve Kidney Transplant Survival in Patients with End-Stage Renal Disease Who are Highly Sensitized to Transplant Antigens
2. A Study of the Safety and Effectiveness of Varivax (the Chicken Pox Vaccine) in Children Who Have Received Kidney Transplants
3. Kidney and Liver Transplantation in People with HIV
4. TThe Role of Connective Tissue Growth Factor in the Development of Kidney Disease After Organ Transplantation
5. A Study To Test An Anti-Rejection Therapy After Kidney Transplantation
Related Studies:
Other Kidney Transplantation Clinical Trials
Other Maryland Clinical Trials
Other Bethesda Clinical Trials
Evaluating the Use of Thymoglobulin, Sirolimus, and Donor Bone Marrow with Kidney Transplantation Patients
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