Effects of Mycophenolate Mofetil On Anti-HLA Antibody Levels In Patients Awaiting Cadaveric Renal Transplant - Full Text View

Sponsors and Collaborators:	University of Washington Hoffmann-La Roche
Information provided by:	University of Washington
ClinicalTrials.gov Identifier:	NCT00446459

Purpose

Increasingly patients who have been pre-sensitized to human tissue by prior transplants, blood transfusion or pregnancy are being added to the kidney transplant waiting list. Currently over 30% of the patients on the national waiting list have a panel reactive antibody (PRA) titer over 9%. 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. With this decreased chance for transplantation comes a decreased rate of survival.

This is a 12-month, phase II, prospective, open label study, to evaluate the effect of mycophenolate mofetil (MMF) on sensitization among patients on the kidney transplant list with high panel of reactive antibody (PRA) levels. Subjects will be their own controls using their average PRA over the prior year, compared to the end of treatment PRA at the 11-month time point and a population control (patients on the transplant wait list who did not participate in this study). The hypothesis for this study is as follows: Mycophenolate mofetil given over 8 months to highly sensitized subjects awaiting kidney transplant, will result in a decrement in the PRA to less than 10% in approximately 40% of patients. This decrement should allow an improved rate of transplantation.

Condition	Intervention	Phase
Kidney Failure, Chronic Diabetic Nephropathies Glomerulonephritis, IGA Hypertension, Renal	Drug: mycophenolate mofetil (CellCept)	Phase II

MedlinePlus related topics: Diabetic Kidney Problems High Blood Pressure Kidney Failure Kidney Transplantation

Drug Information available for: Immunoglobulins Globulin, Immune Mycophenolate Mofetil Mycophenolate mofetil hydrochloride

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	The Highly Sensitized Patients: Effects of Mycophenolate Mofetil On Anti-HLA Antibody Levels In Patients Awaiting Cadaveric Renal Transplant

Further study details as provided by University of Washington:

Primary Outcome Measures:

To determine the number of pre-sensitized patients treated with mycophenolate mofetil manifesting a drop in the PRA to less than 10%. [ Time Frame: 8 months from study start ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To determine the number of pre-sensitized patients treated with mycophenolate mofetil who receive a kidney transplant. [ Time Frame: 12 months from study start ] [ Designated as safety issue: No ]
To determine the average drop in the PRA in subjects treated with mycophenolate mofetil. [ Time Frame: 8 months from study start ] [ Designated as safety issue: No ]
To determine the hematologic effects and development of infection in subjects treated with mycophenolate mofetil. [ Time Frame: Continuously throughout study from months 1 - 12 ] [ Designated as safety issue: Yes ]
To assess for the safety of mycophenolate mofetil treatment in dialysis patients. [ Time Frame: Continuously throughout study from months 1 - 12 ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	30
Study Start Date:	April 2006
Estimated Study Completion Date:	December 2008
Estimated Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Intervention Details:

500mg - 1,000mg, taken PO, twice daily.

Show Detailed Description

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Persons on the kidney transplant waiting list who are currently receiving hemodialysis
Age range 18 - 75
Outpatient status
Patients with a PRA over 50% for over 6 months
Patients with updated immunizations for tetanus, influenza, hepatitis B, pneumococcus
Patients with a PPD (purified protein derivative) test within the last 6 months. If subject has a prior history of TB (tuberculosis) or positive PPD, documentation of adequate treatment is required.
Women who are of childbearing potential must have a negative serum pregnancy test prior to being enrolled in the study and agree to use a medically acceptable method of contraception throughout the study.

Exclusion Criteria:

Active infection
History of multiple recurrent infections defined as more than 3 urinary tract infections, 2 episodes of pneumonia or 3 episodes of otitis/sinusitis in one year, or more than two dialysis line or peritoneal infections within one year. Infection with HCV (hepatitis C virus) or HBV (hepatitis B virus) or HIV (human immunodeficiency virus).
Lack of documentation of PPD testing
Lack of documentation of treatment of a positive PPD
Pregnant or breast-feeding
Baseline leukopenia, WBC < 4.0
Thrombocytopenia (platelet count < 130) or difficult to treat anemia, HCT chronically < 32 on intravenous iron and EPO (erythropoietin) therapy
Transfusion within 6 months

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00446459

Locations

United States, Washington
Universtiy of Washington Medical Center
Seattle, Washington, United States, 98195

Sponsors and Collaborators

University of Washington

Hoffmann-La Roche

Investigators

Principal Investigator:

Connie L Davis, MD

University of Washington

More Information

Publications:

Miura S, Okazaki H, Satoh T, Amada N, Ohashi Y. Long-term follow-up of living donor renal transplant recipients sensitized after donor specific blood transfusion. Transplant Proc. 2001 Feb-Mar;33(1-2):1221-3. No abstract available.

Takeda A, Uchida K, Haba T, Tominaga Y, Katayama A, Kobayashi T, Oikawa T, Morozumi K. Acute humoral rejection of kidney allografts in patients with a positive flow cytometry crossmatch (FCXM). Clin Transplant. 2000;14 Suppl 3:15-20.

Schweitzer EJ, Wilson JS, Fernandez-Vina M, Fox M, Gutierrez M, Wiland A, Hunter J, Farney A, Philosophe B, Colonna J, Jarrell BE, Bartlett ST. A high panel-reactive antibody rescue protocol for cross-match-positive live donor kidney transplants. Transplantation. 2000 Nov 27;70(10):1531-6.

Dafoe DC, Bromberg JS, Grossman RA, Tomaszewski JE, Zmijewski CM, Perloff LJ, Naji A, Asplund MW, Alfrey EJ, Sack M, et al. Renal transplantation despite a positive antiglobulin crossmatch with and without prophylactic OKT3. Transplantation. 1991 Apr;51(4):762-8.

Zanker B, Schleibner S, Schneeberger H, Krauss M, Land W. Mycophenolate mofetil in patients with acute renal failure: evidence of metabolite (MPAG) accumulation and removal by dialysis. Transpl Int. 1996;9 Suppl 1:S308-10.

Kaplan B, Meier-Kriesche HU, Friedman G, Mulgaonkar S, Gruber S, Korecka M, Brayman KL, Shaw LM. The effect of renal insufficiency on mycophenolic acid protein binding. J Clin Pharmacol. 1999 Jul;39(7):715-20.

Haubitz M, de Groot K. Tolerance of mycophenolate mofetil in end-stage renal disease patients with ANCA-associated vasculitis. Clin Nephrol. 2002 Jun;57(6):421-4.

Gloor JM, Lager DJ, Moore SB, Pineda AA, Fidler ME, Larson TS, Grande JP, Schwab TR, Griffin MD, Prieto M, Nyberg SL, Velosa JA, Textor SC, Platt JL, Stegall MD. ABO-incompatible kidney transplantation using both A2 and non-A2 living donors. Transplantation. 2003 Apr 15;75(7):971-7.

Holechek MJ, Hiller JM, Paredes M, Rickard JC, Montgomery RA. Expanding the living organ donor pool: positive crossmatch and ABO incompatible renal transplantation. Nephrol Nurs J. 2003 Apr;30(2):195-204.

Responsible Party:	University of Washington ( Dr. Connie Davis )
Study ID Numbers:	03-7915A-05
Study First Received:	March 9, 2007
Last Updated:	February 14, 2008
ClinicalTrials.gov Identifier:	NCT00446459
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Washington:

Dialysis
Kidney
Renal
Nephropathy
Glomerulonephropathy
Immunosuppression
Allograft
Compatibility

HLA
PRA
Transplant
Sensitization
Antibodies
Diabetes
Hypertension
Transplantation, Kidney

Study placed in the following topic categories:

Renal Insufficiency
Glomerulonephritis
Autoimmune Diseases
Diabetic Nephropathies
Mycophenolic Acid
Vascular Diseases
Kidney Failure, Chronic
Diabetes Mellitus
Endocrine System Diseases
Hypertension, Renal
Antibodies
Urologic Diseases

Renal Insufficiency, Chronic
Nephritis
Renal hypertension
Mycophenolate mofetil
Berger disease
Glomerulonephritis, IGA
Endocrinopathy
Kidney Diseases
Diabetes Complications
Immunoglobulins
Kidney Failure
Hypertension

Additional relevant MeSH terms:

Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Immune System Diseases
Antineoplastic Agents
Therapeutic Uses
Physiological Effects of Drugs

Enzyme Inhibitors
Cardiovascular Diseases
Antibiotics, Antineoplastic
Immunosuppressive Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009