Ignite Creation Date:
2024-05-05 @ 11:22 AM
Last Modification Date:
2024-10-26 @ 9:05 AM
Study NCT ID:
NCT00006178
Status:
COMPLETED
Last Update Posted:
2019-09-17
First Post:
2000-08-15
Brief Title:
Sirolimus and Thymoglobulin to Prevent Kidney Transplant Rejection
Sponsor:
National Institute of Diabetes and Digestive and Kidney Diseases NIDDK
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Sirolimus Monotherapy to Optimize Activation Induced Cell Death AICD in Renal Transplants Following Lymphocyte Depletion Induction With Thymoglobulin
Status:
COMPLETED
Status Verified Date:
2010-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will test the safety and effectiveness of two drugs Sirolimus and Thymoglobulin for preventing rejection of transplanted kidneys Standard anti-rejection therapy uses a combination of drugs such as cyclosporine tacrolimus azathioprine steroids and others that are taken daily for life However even with this daily therapy more than half of kidney recipients slowly reject their transplant within 10 years Both Thymoglobulin an antibody and Sirolimus an anti-rejection drug prevent rejection by lowering the response of the immune system to the transplanted organ Thymoglobulin is given in the pre- and postoperative period and Sirolimus is taken long term
Patients who receive a kidney transplant at the National Institutes of Health Clinical Center are eligible for this study Candidates will be screened with a medical history physical examination and blood and urine tests
Participants will undergo a kidney transplant Before the surgery a central line intravenous catheter through which blood and medicine can be given is placed in the neck or chest Patients may also undergo leukapheresis a procedure for collecting white blood cells The cells can be stored for transfusion later if white cell counts drop following Thymoglobulin treatment For this procedure blood is drawn from a needle placed in the arm and flows into a machine that separates the blood components by spinning The white cells are collected in a bag and the red cells and plasma are returned through a second needle in the other arm
Thymoglobulin will be given intravenously the day before the transplant and days 1 through 9 after the operation Sirolimus will be taken by mouth mixed with water or orange juice Sirolimus therapy starts the day of the transplant and continues for life
Follow-up study visits will be scheduled weekly for the first month after the transplant then every 6 months for 1 year and then once a year for 4 years Procedures during these visits may include blood and urine tests physical examination and check of vital signs ie blood pressure heart rate breathing rate temperature Kidney biopsies removal of a small piece of tissue for examination under the microscope will be done at 2 weeks 1 month and 6 months after surgery and then yearly for 4 years to check for any damage to the kidney In addition a local doctor will do routine laboratory tests 2 to 3 times a week for the first 2 to 3 months aft
Patients who receive a kidney transplant at the National Institutes of Health Clinical Center are eligible for this study Candidates will be screened with a medical history physical examination and blood and urine tests
Participants will undergo a kidney transplant Before the surgery a central line intravenous catheter through which blood and medicine can be given is placed in the neck or chest Patients may also undergo leukapheresis a procedure for collecting white blood cells The cells can be stored for transfusion later if white cell counts drop following Thymoglobulin treatment For this procedure blood is drawn from a needle placed in the arm and flows into a machine that separates the blood components by spinning The white cells are collected in a bag and the red cells and plasma are returned through a second needle in the other arm
Thymoglobulin will be given intravenously the day before the transplant and days 1 through 9 after the operation Sirolimus will be taken by mouth mixed with water or orange juice Sirolimus therapy starts the day of the transplant and continues for life
Follow-up study visits will be scheduled weekly for the first month after the transplant then every 6 months for 1 year and then once a year for 4 years Procedures during these visits may include blood and urine tests physical examination and check of vital signs ie blood pressure heart rate breathing rate temperature Kidney biopsies removal of a small piece of tissue for examination under the microscope will be done at 2 weeks 1 month and 6 months after surgery and then yearly for 4 years to check for any damage to the kidney In addition a local doctor will do routine laboratory tests 2 to 3 times a week for the first 2 to 3 months aft
Detailed Description:
This protocol will test a novel dual agent combination therapy for its ability to prevent human renal allograft rejection Thymoglobulin Sangstat a FDA-approved polyclonal rabbit-IgG antithymocyte preparation will be given for ten days at the time of transplantation to achieve profound lymphocyte depletion This will be paired with chronic therapy with Sirolimus rapamycin Wyeth-Ayerst an oral immunosuppressant agent recently approved by the FDA Rapamycin allows for antigen specific T cell activation but prevents T cell clonal expansion by interrupting IL-2 receptor beta-chain signal transduction The rationale for this combination is to eliminate existing alloreactive T cell clones that could initiate a rejection at the time of transplantation and to promote graft specific activation induced cell death AICD in repopulating T cells such that an allospecific T cell deficit is induced The desired effect of this therapy is to prevent allograft rejection without the chronic use of calcineurin inhibitors or glucocorticosteroids and in doing so develop a regimen for transplantation that avoids most of the chronic drug toxicities inherent in the use of these two classes of immunosuppressants
Twenty people will be evaluated in this pilot protocol Ten will receive living donor kidney allografts and ten will receive cadaveric kidney allografts Patients will be treated with Thymoglobulin beginning prior to graft implantation and continuing for ten days Glucocorticosteroids will be given during the Thymoglobulin treatment to limit monocyte activation and prevent the cytokine release syndrome associated with this antibody preparation Patients will be given Sirolimus orally beginning the day after transplantation and continuously thereafter 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 a specific desired effect allospecific AICD that should promote the development of allospecific graft tolerance This will be accomplished by assaying peripheral blood and allograft biopsies for apoptosis and peripheral blood for evidence of alloreactive T cell clone depletion
Twenty people will be evaluated in this pilot protocol Ten will receive living donor kidney allografts and ten will receive cadaveric kidney allografts Patients will be treated with Thymoglobulin beginning prior to graft implantation and continuing for ten days Glucocorticosteroids will be given during the Thymoglobulin treatment to limit monocyte activation and prevent the cytokine release syndrome associated with this antibody preparation Patients will be given Sirolimus orally beginning the day after transplantation and continuously thereafter 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 a specific desired effect allospecific AICD that should promote the development of allospecific graft tolerance This will be accomplished by assaying peripheral blood and allograft biopsies for apoptosis and peripheral blood for evidence of alloreactive T cell clone depletion
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 00-DK-0196 | OTHER | NIDDKNIH | None |