Ignite Creation Date:
2024-05-05 @ 5:22 PM
Last Modification Date:
2024-10-26 @ 9:31 AM
Study NCT ID:
NCT00446459
Status:
COMPLETED
Last Update Posted:
2010-04-15
First Post:
2007-03-09
Brief Title:
Effects of Mycophenolate Mofetil MMF On Anti-HLA Human Leukocyte AntigenAntibody Levels In Patients Awaiting Cadaveric Renal Transplant
Sponsor:
University of Washington
Organization:
University of Washington
Study Overview
Official Title:
The Highly Sensitized Patients Effects of Mycophenolate Mofetil MMF On Anti-Human Leukocyte Antigen HLA Antibody Levels In Patients Awaiting Cadaveric Renal Transplant
Status:
COMPLETED
Status Verified Date:
2010-04
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 is a 12-month phase II prospective open label study to evaluate the effect of mycophenolate mofetil MMF among patients on the kidney transplant list with high Panel of Reactive Antibody PRA levels
On average increasing the PRA from 0 to 50 specifically in the Washington Organ Procurement Organization OPO increases the waiting time from 3 to 6 years Spontaneous decreases in the PRA rarely occur and is associated with a decreased chance for transplantation and a decreased rate of survival
On average increasing the PRA from 0 to 50 specifically in the Washington Organ Procurement Organization OPO increases the waiting time from 3 to 6 years Spontaneous decreases in the PRA rarely occur and is associated with a decreased chance for transplantation and a decreased rate of survival
Detailed Description:
HYPOTHESIS mycophenolate mofetil given over 8 months to highly sensitized subjects awaiting kidney transplant will result in a decrement in the PRA by 10 or more in approximately 40 of patients This decrement should allow an improved rate of transplantation
BACKGROUND Patients who have been exposed to human tissue by prior transplants blood transfusion or pregnancy may develop anti-bodies against the cell markers of human white blood cells called Human Leukocyte Antigens HLA Preformed anti-bodies to these foreign human tissues is called SENSITIZATION Sensitized patients are more likely to reject a kidney from a donor who possesses the antigenic profile to which they are already sensitized This limits the recipients possible donor pool out of the general population
The Panel of Reactive Antibodies PRA is a test panel that represents the HLA antigenic profile of the local community The test panel is used to measure the recipients reactivity by percent to a variety of HLA antigens A PRA of 75 means the patient reacted to 75 of the antigens on the test panel A PRA panel greater than 50 indicates that the subject potential organ recipient already has a significant number of antibodies pre-formed to other human tissue and is highly sensitized Spontaneous decreases in PRA titers rarely occur thus the probability of transplantation in sensitized patients is significantly decreased
STUDY POPULATION adult University of Washington Medical Center patients on the kidney transplant waiting list who are currently receiving dialysis with a PRA level over 50 and for a period of 6 months or longer
TREATMENT PLAN INTERVENTION
CONSENT Consent will be obtained from all subjects SCREENING Prior to starting MMF a thorough medical history physical exam will be obtained Patients will be screened clinically for occurrence of infection and for protective antibodies in response to prior vaccinations and assure that they are up to date with their immunizations
INVESTIGATIONAL PRODUCT Mycophenolate mofetil MMF is used as a routine therapy for the prevention of rejection in transplant recipients and is also used routinely for the treatment of autoimmune disease and primary renal diseases such as IgA nephropathy and lupus nephritis
HOFFMANN LA ROCHE Will provide Mycophenolate mofetil MMF as CellCept well as costs for laboratory testing
DOSAGE AND ADMINISTRATION MMF will be dispensed by investigational drug pharmacists in 250mg capsules taken orally twice daily Dosing of MMF will begin at 500 mg bid for 30 days then increased to 1 gm bid if subject is not experiencing undo gastrointestinal side effects or a decrease in WBC
STUDY DESIGN
The subjects will be continually evaluated for 12 months Month 4 If the subjects PRA drops by 10 at month 4 subject will remain on MMF without any changes If subjects PRA does NOT drop by 10 at month four and infections have NOT occurred subject will remain on MMF and increase dosage if possible
If at month four more than 4 serious infections have occurred the MMF dose will be reduced and or stopped for that subject If stopped they will be followed for 4 months
Month 8
If the subjects PRA does NOT drop by 10 at month 8 the MMF will be discontinued and the subject will be followed for the next 4 months to month 12 post enrollment
If subjects PRA DOES drop by 10 at month 8 and NO infections have occurred subject will continue on MMF to month 12 Study subjects will be followed for a maximum of 12 months
OBJECTIVES
The primary endpoint
1 The number of subjects who achieve a PRA reduction of 10 or greater within 8 months of initiating mycophenolate mofetil MMFtherapy
The secondary outcome measures will include
1 The number of subjects who received a transplant during the study
2 The number of subjects who experienced Institutional Review Board IRB reportable infections
3 The number of subjects whos white blood cell count WBC or Immunoglobulin G or M IgG IgM titers are below range
4 The number of transplants with a negative crossmatch
CLINICAL AND LABORATORY EVALUATIONS
LAB ASSESSMENT
Immunology PRA panel of reactive antibodies will be taken monthly and the levels of individual HLA anti-bodies will be evaluated every other month
Safety
Total levels of Immunoglobulin G IgG and Immunoglobulin M IgM as measures of the indigenous anti-body population levels As well as HepB surface Antibody and CMV are tests done to monitor to screen for changes in the health of the subjects immune system ie loss of memory for immunization
A complete blood count CBC is taken at each visit to screen for anemia Differential analysis on CBD for screening against platelet reduction and possible bone marrow suppression The subjects CBC will be checked more frequently if hisher WBC hematocrit or platelets are low Subjects will be followed closely through 12 months
BACKGROUND Patients who have been exposed to human tissue by prior transplants blood transfusion or pregnancy may develop anti-bodies against the cell markers of human white blood cells called Human Leukocyte Antigens HLA Preformed anti-bodies to these foreign human tissues is called SENSITIZATION Sensitized patients are more likely to reject a kidney from a donor who possesses the antigenic profile to which they are already sensitized This limits the recipients possible donor pool out of the general population
The Panel of Reactive Antibodies PRA is a test panel that represents the HLA antigenic profile of the local community The test panel is used to measure the recipients reactivity by percent to a variety of HLA antigens A PRA of 75 means the patient reacted to 75 of the antigens on the test panel A PRA panel greater than 50 indicates that the subject potential organ recipient already has a significant number of antibodies pre-formed to other human tissue and is highly sensitized Spontaneous decreases in PRA titers rarely occur thus the probability of transplantation in sensitized patients is significantly decreased
STUDY POPULATION adult University of Washington Medical Center patients on the kidney transplant waiting list who are currently receiving dialysis with a PRA level over 50 and for a period of 6 months or longer
TREATMENT PLAN INTERVENTION
CONSENT Consent will be obtained from all subjects SCREENING Prior to starting MMF a thorough medical history physical exam will be obtained Patients will be screened clinically for occurrence of infection and for protective antibodies in response to prior vaccinations and assure that they are up to date with their immunizations
INVESTIGATIONAL PRODUCT Mycophenolate mofetil MMF is used as a routine therapy for the prevention of rejection in transplant recipients and is also used routinely for the treatment of autoimmune disease and primary renal diseases such as IgA nephropathy and lupus nephritis
HOFFMANN LA ROCHE Will provide Mycophenolate mofetil MMF as CellCept well as costs for laboratory testing
DOSAGE AND ADMINISTRATION MMF will be dispensed by investigational drug pharmacists in 250mg capsules taken orally twice daily Dosing of MMF will begin at 500 mg bid for 30 days then increased to 1 gm bid if subject is not experiencing undo gastrointestinal side effects or a decrease in WBC
STUDY DESIGN
The subjects will be continually evaluated for 12 months Month 4 If the subjects PRA drops by 10 at month 4 subject will remain on MMF without any changes If subjects PRA does NOT drop by 10 at month four and infections have NOT occurred subject will remain on MMF and increase dosage if possible
If at month four more than 4 serious infections have occurred the MMF dose will be reduced and or stopped for that subject If stopped they will be followed for 4 months
Month 8
If the subjects PRA does NOT drop by 10 at month 8 the MMF will be discontinued and the subject will be followed for the next 4 months to month 12 post enrollment
If subjects PRA DOES drop by 10 at month 8 and NO infections have occurred subject will continue on MMF to month 12 Study subjects will be followed for a maximum of 12 months
OBJECTIVES
The primary endpoint
1 The number of subjects who achieve a PRA reduction of 10 or greater within 8 months of initiating mycophenolate mofetil MMFtherapy
The secondary outcome measures will include
1 The number of subjects who received a transplant during the study
2 The number of subjects who experienced Institutional Review Board IRB reportable infections
3 The number of subjects whos white blood cell count WBC or Immunoglobulin G or M IgG IgM titers are below range
4 The number of transplants with a negative crossmatch
CLINICAL AND LABORATORY EVALUATIONS
LAB ASSESSMENT
Immunology PRA panel of reactive antibodies will be taken monthly and the levels of individual HLA anti-bodies will be evaluated every other month
Safety
Total levels of Immunoglobulin G IgG and Immunoglobulin M IgM as measures of the indigenous anti-body population levels As well as HepB surface Antibody and CMV are tests done to monitor to screen for changes in the health of the subjects immune system ie loss of memory for immunization
A complete blood count CBC is taken at each visit to screen for anemia Differential analysis on CBD for screening against platelet reduction and possible bone marrow suppression The subjects CBC will be checked more frequently if hisher WBC hematocrit or platelets are low Subjects will be followed closely through 12 months
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 |
|---|---|---|---|
| 03-7915-A | None | None | None |