Clinical Trial: Effects of Mycophenolate Mofetil (MMF) On Anti-HLA (Human Leukocyte Antigen)Antibody Levels In Patients Awaiting Cadaveric Renal Transplant.

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

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.

Detailed Summary:

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 recipient's 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 recipient's 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 obta
Sponsor: University of Washington

Current Primary Outcome: The Number of Subjects With a 10% Decrease in PRA Level at Month 8. [ Time Frame: Enrollment to month 8 ]

Original Primary Outcome: To determine the number of pre-sensitized patients treated with mycophenolate mofetil manifesting a drop in the PRA to less than 10%.

Current Secondary Outcome:

• The Number of Subjects With Significant Infections up to Month 12. [ Time Frame: From enrollment to month 12. ]
  The number of infections while on-study up to month 12. Subjects who's PRA decreased by 10% at month 8 and who went on to the Mycophenolate mofetil + Rituximab study were followed to month 8. Those subjects who stayed on the Mycophenolate mon-therapy study were observed for infection over 12 months or until they seperated from the study.
• The Number of Kidney Transplant up to 12 Months. [ Time Frame: Enrollment to month 8 or month 12 post enrollment. ]
  The number of kidney transplants up to month 12. Subjects who's PRA decreased by 10% at month 8 and who went on to the Mycophenolate mofetil + Rituximab study were followed to month 8. Those subjects who stayed on the Mycophenolate mon-therapy study were observed for infection over 12 months or until they seperated from the study.
• The Number of Pariticpants With a White Blood Cell Count Below 2.0 Thousand (Low) or Total IgG/IgM Titers Below Range (620-1490 mg/dL). [ Time Frame: Enrollment to month 12. ]
  The number of subjects with adverse hematologic effects with MMF while on-study. Subjects who's PRA decreased by 10% at month 8 and who went on to the Mycophenolate mofetil + Rituximab study were followed to month 8. Those subjects who stayed on the Mycophenolate mon-therapy study were observed for hematologic effects up to 12 months.
• The Number of Transplants With a Negative Crossmatch at Transplant. [ Time Frame: Number of Transplants with a Negative Crossmatch. ]
  The number negative crossmatch transplants up to month 12. Positivie crossmatch transplant carries a higher risk for rejection. Subjects who's PRA decreased by 10% at month 8 and who went on to the Mycophenolate mofetil + Rituximab study were followed to month 8. Those subjects who stayed on the Mycophenolate mon-therapy study were observed for negative crossmatch transplants to 12 months.

Original Secondary Outcome:

• To determine the number of pre-sensitized patients treated with mycophenolate mofetil who receive a kidney transplant.
• To determine the average drop in the PRA in subjects treated with mycophenolate mofetil.
• To determine the hematologic effects and development of infection in subjects treated with mycophenolate mofetil.
• To assess for the safety of mycophenolate mofetil treatment in dialysis patients.

Dates:
Date Received: March 9, 2007
Date Started: April 2006
Date Completion:
Last Updated: April 5, 2010
Last Verified: April 2010