Effects of Mycophenolate Mofetil (MMF) On Anti-HLA (Human Leukocyte Antigen)Antibody Levels In Patients Awaiting Cadaveric Renal Transplant. - Full Text View

Purpose

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.

Condition	Intervention	Phase
Kidney Failure, Chronic Diabetic Nephropathies Glomerulonephritis, IGA Hypertension, Renal	Drug: mycophenolate mofetil (CellCept)	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

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

Drug Information available for: Mycophenolic acid Mycophenolate sodium Mycophenolate mofetil hydrochloride Mycophenolate mofetil

U.S. FDA Resources

Further study details as provided by University of Washington:

Primary Outcome Measures:

The Number of Subjects With a 10% Decrease in PRA Level at Month 8. [ Time Frame: Enrollment to month 8 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

The Number of Subjects With Significant Infections up to Month 12. [ Time Frame: From enrollment to month 12. ] [ Designated as safety issue: Yes ]
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. ] [ Designated as safety issue: No ]
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. ] [ Designated as safety issue: Yes ]
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. ] [ Designated as safety issue: No ]
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.

Enrollment:	45
Study Start Date:	April 2006
Study Completion Date:	December 2008
Primary Completion Date:	November 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:	Dr. Connie Davis, University of Washington
ClinicalTrials.gov Identifier:	NCT00446459 History of Changes
Other Study ID Numbers:	24223-A, 03-7915-A
Study First Received:	March 9, 2007
Results First Received:	December 29, 2009
Last Updated:	April 5, 2010
Health Authority:	United States: Food and Drug Administration United States: Institutional Review Board

Keywords provided by University of Washington:

CellCept
Dialysis
Kidney
Renal
Nephropathy
Glomerulonephropathy
Immunosuppression
Allograft
Compatibility

HLA
PRA
Transplant
Sensitization
Antibodies
Diabetes
Hypertension
Transplantation, Kidney

Additional relevant MeSH terms:

Diabetic Nephropathies
Glomerulonephritis
Glomerulonephritis, IGA
Hypertension
Hypertension, Renal
Kidney Diseases
Kidney Failure, Chronic
Renal Insufficiency
Urologic Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Nephritis
Autoimmune Diseases
Immune System Diseases

Vascular Diseases
Cardiovascular Diseases
Renal Insufficiency, Chronic
Antibodies
Mycophenolate mofetil
Mycophenolic Acid
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 19, 2013