Ignite Creation Date:
2024-05-05 @ 11:29 AM
Last Modification Date:
2024-10-26 @ 9:08 AM
Study NCT ID:
NCT00056784
Status:
COMPLETED
Last Update Posted:
2017-10-06
First Post:
2003-03-22
Brief Title:
The Role of Connective Tissue Growth Factor in the Development of Kidney Disease After Organ Transplantation
Sponsor:
National Institute of Diabetes and Digestive and Kidney Diseases NIDDK
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
The Pathogenesis of Chronic Graft Failure After Kidney Transplantation
Status:
COMPLETED
Status Verified Date:
2014-06-17
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 examine whether measurements of connective tissue growth factor CTGF and other cell proteins can identify which kidney transplant recipients are likely to develop chronic allograft nephropathy CAN a disease of the transplanted kidney CAN may occur months to years after the transplant The kidney becomes progressively scarred and eventually loses all function so that dialysis or another transplant is needed A better understanding of how CTGF and other proteins are involved in the development of CAN may provide new targets for treating for the disease
Patients who are scheduled to receive a kidney or combined kidney-pancreas transplant or who have received a transplant recently within 6 months may be eligible for this study Participants will be enrolled before the transplant if possible or after the transplant and will undergo the following tests and procedures
Physical examinations at the screening visit at 1 6 12 and 24 months and then once yearly
Blood sample collections at the screening visit at 1 6 12 18 and 24 months and then once yearly
Urine sample collections at the screening visit at 1 6 12 18 and 24 months and then once yearly
Kidney biopsies at the beginning of the study at 1 6 12 and 24 months and then once a year for research purposes Participants may refuse to have a research biopsy at any time during the study Also patients who are having a kidney biopsy for another reason at these time points will not have a second biopsy The biopsy procedure takes about 15 minutes and is done in the hospital The patient lies on his or her back and the skin over the transplanted kidney is cleaned with alcohol and iodine The area is numbed with an injection of an anesthetic and then a biopsy needle is placed through the kin The biopsy may be repeated up to three times to get enough tissue to test for CAN Patients lie flat for 4 hours after the procedure to reduce the risk of bleeding and are observed for another 2 hours for possible complications
Patients who are scheduled to receive a kidney or combined kidney-pancreas transplant or who have received a transplant recently within 6 months may be eligible for this study Participants will be enrolled before the transplant if possible or after the transplant and will undergo the following tests and procedures
Physical examinations at the screening visit at 1 6 12 and 24 months and then once yearly
Blood sample collections at the screening visit at 1 6 12 18 and 24 months and then once yearly
Urine sample collections at the screening visit at 1 6 12 18 and 24 months and then once yearly
Kidney biopsies at the beginning of the study at 1 6 12 and 24 months and then once a year for research purposes Participants may refuse to have a research biopsy at any time during the study Also patients who are having a kidney biopsy for another reason at these time points will not have a second biopsy The biopsy procedure takes about 15 minutes and is done in the hospital The patient lies on his or her back and the skin over the transplanted kidney is cleaned with alcohol and iodine The area is numbed with an injection of an anesthetic and then a biopsy needle is placed through the kin The biopsy may be repeated up to three times to get enough tissue to test for CAN Patients lie flat for 4 hours after the procedure to reduce the risk of bleeding and are observed for another 2 hours for possible complications
Detailed Description:
Following transplantation recipients of organ allografts are placed on immunosuppression indefinitely Despite dramatic improvements in acute rejection rates and short-term graft survival long term graft survival has not changed appreciably over the past 20 years In kidney transplantation the leading cause of late graft loss is chronic allograft nephropathy CAN This disorder is clinically characterized by a progressive decline in kidney function associated with the characteristic histologic features of interstitial fibrosis and inflammation arteriosclerosis glomerulosclerosis and tubular atrophy Both immunologic and non-immunologic factors have been implicated in the development of CAN However the etiology of this disorder has not been clearly defined nor is there specific therapy for treating CAN
Implicated in the development of CAN in rodents and humans is transforming growth factor beta TGF-beta a pleiotropic cytokine which is elevated in CAN recipients and stimulates matrix deposition within the graft A downstream effector of TGF-b is connective tissue growth factor CTGF which has been recently associated with other fibrotic renal diseases In preliminary studies in a mouse model of CAN CTGF gene expression is increased in kidney transplants with CAN However its role in human CAN is unknown
The aim of this investigation is to identify whether CTGF may play a role in the pathogenesis of CAN in humans Our long-term objective is to determine whether CTGF and other cytokine mediators may be novel targets for the therapy of CAN Our goals are to 1 Determine the level of CTGF expressed in the urine and serum CTGF of recipients of kidney transplants 2 Identify whether urinary or serum CTGF might be a marker of CAN and be utilized as a predictor for those at risk to develop the disease 3 Identify other molecular messages and proteins that may identify the development of CAN as potential future targets of treatment
In this prospective study serial urine and serum samples will be obtained in recipients before during and after transplantation of a kidney allograft The graft will be monitored in the context of standard measures of renal function which include serum creatinine and creatinine clearance These results will be correlated with other clinically descriptive information regarding the recipient s transplant
Implicated in the development of CAN in rodents and humans is transforming growth factor beta TGF-beta a pleiotropic cytokine which is elevated in CAN recipients and stimulates matrix deposition within the graft A downstream effector of TGF-b is connective tissue growth factor CTGF which has been recently associated with other fibrotic renal diseases In preliminary studies in a mouse model of CAN CTGF gene expression is increased in kidney transplants with CAN However its role in human CAN is unknown
The aim of this investigation is to identify whether CTGF may play a role in the pathogenesis of CAN in humans Our long-term objective is to determine whether CTGF and other cytokine mediators may be novel targets for the therapy of CAN Our goals are to 1 Determine the level of CTGF expressed in the urine and serum CTGF of recipients of kidney transplants 2 Identify whether urinary or serum CTGF might be a marker of CAN and be utilized as a predictor for those at risk to develop the disease 3 Identify other molecular messages and proteins that may identify the development of CAN as potential future targets of treatment
In this prospective study serial urine and serum samples will be obtained in recipients before during and after transplantation of a kidney allograft The graft will be monitored in the context of standard measures of renal function which include serum creatinine and creatinine clearance These results will be correlated with other clinically descriptive information regarding the recipient s transplant
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 |
|---|---|---|---|
| 03-DK-0132 | None | None | None |