Ignite Creation Date:
2024-05-05 @ 11:57 AM
Last Modification Date:
2024-10-26 @ 9:17 AM
Study NCT ID:
NCT00198224
Status:
COMPLETED
Last Update Posted:
2005-09-20
First Post:
2005-09-13
Brief Title:
Immunosuppressive Effects of Mycophenolate Mofetil and Valganciclovir in Kidney Transplant Recipients
Sponsor:
Indiana University School of Medicine
Organization:
Indiana University
Study Overview
Official Title:
Pilot Study of In Vitro Immunosuppressive Effects of Mycophenolate Mofetil and Valganciclovir in Kidney Transplant Recipients
Status:
COMPLETED
Status Verified Date:
2004-11
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:
Valganciclovir VGCV has recently been approved by the Food and Drug Administration FDA for the treatment and prevention of cytomegalovirus CMV retinitis in HIV patients It is under review for the prevention of CMV disease following organ transplantation Mycophenolate mofetil MMF the morpholinoethyl ester of mycophenolic acid MPA is currently the most widespread used immunosuppressant in kidney transplantation These drugs exerts their effects by blocking the production of DNA primarily in lymphocytes
Recent studies have suggested that combining both MMF and GCV in vitro may have a beneficial effect on the treatment of CMV infections However the effect of these two drugs in combination on the effects of the immune system both in vitro and in vivo have not been studied Preliminary studies in our lab show that a combination of these two drugs have an additive effect on the level of immunosuppression of both the growth and differentiation of progenitor bone marrow cells as well as lymphocyte proliferation
This study is designed to test patients degree of immune reactivity both on and off VGCV when used in combination with MMF Patients will have blood drawn as several time points and an immune assay will be performed to show if VGCV when used in combination with MMF exerts immunosuppressive effects
Recent studies have suggested that combining both MMF and GCV in vitro may have a beneficial effect on the treatment of CMV infections However the effect of these two drugs in combination on the effects of the immune system both in vitro and in vivo have not been studied Preliminary studies in our lab show that a combination of these two drugs have an additive effect on the level of immunosuppression of both the growth and differentiation of progenitor bone marrow cells as well as lymphocyte proliferation
This study is designed to test patients degree of immune reactivity both on and off VGCV when used in combination with MMF Patients will have blood drawn as several time points and an immune assay will be performed to show if VGCV when used in combination with MMF exerts immunosuppressive effects
Detailed Description:
Recruitment and screening of subjects will be performed between 4 and 8 weeks after transplantation at which time consent will be obtained Per clinical standard of care at Indiana University VGCV is routinely stopped at 12 weeks post transplantation At week 10 and the day of discontinuation of their prophylaxis the patients will be seen by the study physician The subjects will also be seen at 2 and 4 weeks after discontinuing VGCV At each study visit the subject will have a limited history and physical HP performed one 3ml light green top lithium heparin tube one 3ml dark green top sodium heparin tube and one 5ml purple top EDTA tube will be obtained by phlebotomy during their regularly scheduled blood draw times This blood will then be used for the Cylex assay Flow cytometry and MMF and GCV trough level The patients complete blood count and differential as well as drug levels and medication dosages will be recorded This information will be used for assure that Cylex results are not being influenced by changes in immunosuppressive drug levels The complete blood count and differential will be used to determine absolute neutrophil counts After the week sixteen visit the subjects will have completed the protocol Pregnancy tests will not be performed as patients are not directly receiving any treatment secondary to this study Flow cytometry will be performed to measure absolute CD4 counts CD4CD8 ratios and look at several activation markers on lymphocytes
Signed IRB approved informed consent must be obtained from all subjects prior to screening assessments The following evaluations will be performed prior to initiation of phlebotomy for purposes of this study
Medical history including age gender race and renal disease immunosuppressive regimen including dose level and use of antibody treatment at time of transplant will be noted
Physical examination including vital signs cardiac and lung evaluation
Laboratory testing which will be performed as part of standard of care because of the transplant are
Hematology complete blood count Drug level tacrolimus cyclosporine andor sirolimus
Evaluations during treatment and post treatment
Patients will be followed by surgical co-investigators throughout the entire study
A limited history and physical examination will be performed as indicated in the schedule of assessments
Clinical laboratory testing Additional clinical laboratory testing beyond standard of care that will be done for this protocol includes adding a differential to the complete blood count CBC and drug levels will be noted from already scheduled clinic appointments and post transplant protocols Research blood levels for GCV and MPA will be run from a 3ml lithium heparin and a 5ml EDTA tube in the research laboratory or at outside laboratory
Transplant laboratory testing On the testing days an additional 3ml sodium heparin blood tube will be drawn in phlebotomy at the same time the scheduled labs are obtained Flow cytometric analysis will be performed at times listed above A 5 tube panel using three color analysis will be performed using approximately 500_L of whole blood from the sodium heparinized tube The panel will consist of the following staining protocol
Tube 1 - CD 45 FITC CD 14 PE - Used to locate lymphocyte population as well as determine purity of specimen and monocyte contamination
Tube 2 - _1a FITC _1a PE _1a PerCP - Isotype control to check for background staining
Tube 3 - CD 4 FITC CD 8 PE CD 20 PerCP - Used to determine CD4CD8 ratio as well as determining B cell population counts
Tube 4 - CD 4 FITC CD 25 PE HLA - DR PerCP - Check for specific activation markers on CD 4 cells
Tube 5 - CD 4 FITC CD 69 PE CD 3 PerCP - Used to get true CD4 counts on T-cells as well as look at another activation marker on CD4 cells
Cylex immune assay will be run as listed above This assay requires minimal amount of whole sodium heparinized blood and will be used from same tube as flow analyses The whole blood is diluted with a saline base diluent It is then stimulated overnight with phytohemagglutinin The CD4 or CD3 T cells are then isolated using magnetic beads They are lysed and ATP production is recorded using a luciferase based reaction
Signed IRB approved informed consent must be obtained from all subjects prior to screening assessments The following evaluations will be performed prior to initiation of phlebotomy for purposes of this study
Medical history including age gender race and renal disease immunosuppressive regimen including dose level and use of antibody treatment at time of transplant will be noted
Physical examination including vital signs cardiac and lung evaluation
Laboratory testing which will be performed as part of standard of care because of the transplant are
Hematology complete blood count Drug level tacrolimus cyclosporine andor sirolimus
Evaluations during treatment and post treatment
Patients will be followed by surgical co-investigators throughout the entire study
A limited history and physical examination will be performed as indicated in the schedule of assessments
Clinical laboratory testing Additional clinical laboratory testing beyond standard of care that will be done for this protocol includes adding a differential to the complete blood count CBC and drug levels will be noted from already scheduled clinic appointments and post transplant protocols Research blood levels for GCV and MPA will be run from a 3ml lithium heparin and a 5ml EDTA tube in the research laboratory or at outside laboratory
Transplant laboratory testing On the testing days an additional 3ml sodium heparin blood tube will be drawn in phlebotomy at the same time the scheduled labs are obtained Flow cytometric analysis will be performed at times listed above A 5 tube panel using three color analysis will be performed using approximately 500_L of whole blood from the sodium heparinized tube The panel will consist of the following staining protocol
Tube 1 - CD 45 FITC CD 14 PE - Used to locate lymphocyte population as well as determine purity of specimen and monocyte contamination
Tube 2 - _1a FITC _1a PE _1a PerCP - Isotype control to check for background staining
Tube 3 - CD 4 FITC CD 8 PE CD 20 PerCP - Used to determine CD4CD8 ratio as well as determining B cell population counts
Tube 4 - CD 4 FITC CD 25 PE HLA - DR PerCP - Check for specific activation markers on CD 4 cells
Tube 5 - CD 4 FITC CD 69 PE CD 3 PerCP - Used to get true CD4 counts on T-cells as well as look at another activation marker on CD4 cells
Cylex immune assay will be run as listed above This assay requires minimal amount of whole sodium heparinized blood and will be used from same tube as flow analyses The whole blood is diluted with a saline base diluent It is then stimulated overnight with phytohemagglutinin The CD4 or CD3 T cells are then isolated using magnetic beads They are lysed and ATP production is recorded using a luciferase based reaction
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 |
|---|---|---|---|
| VAL074 | None | None | None |