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

NCT00446459 | Completed Phase 2 Results DMC

• 2 other identifiers: 24223-A03-7915-A
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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.

Conditions

Kidney Failure, Chronic; Diabetic Nephropathies; Glomerulonephritis, IGA; Hypertension, Renal

Keywords

CellCept; Dialysis; Kidney; Renal; Nephropathy; Glomerulonephropathy; Immunosuppression; Allograft; Compatibility; HLA; PRA; Transplant; Sensitization; Antibodies; Diabetes; Hypertension; Transplantation, Kidney

Outcome Measures

Primary Outcomes (1)

• The Number of Subjects With a 10% Decrease in PRA Level at Month 8.

  Enrollment to month 8

Secondary Outcomes (4)

• The Number of Subjects With Significant Infections up to Month 12.

  From enrollment to month 12.

• The Number of Kidney Transplant up to 12 Months.

  Enrollment to month 8 or month 12 post enrollment.

• 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).

  Enrollment to month 12.

• The Number of Transplants With a Negative Crossmatch at Transplant.

  Number of Transplants with a Negative Crossmatch.

Interventions

mycophenolate mofetil (CellCept) DRUG

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

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Washington: lead
• Hoffmann-La Roche: collaborator

Study Sites (1)

Universtiy of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Related Publications (9)

• 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. doi: 10.1016/s0041-1345(00)02395-2. No abstract available.

  PMID: 11267267 BACKGROUND

• 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. doi: 10.1034/j.1399-0012.2000.0140s3015.x.

  PMID: 11092347 BACKGROUND

• 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. doi: 10.1097/00007890-200011270-00023.

  PMID: 11118102 BACKGROUND

• 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. doi: 10.1097/00007890-199104000-00005.

  PMID: 2014527 BACKGROUND

• 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. doi: 10.1007/978-3-662-00818-8_76.

  PMID: 8959852 BACKGROUND

• 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. doi: 10.1177/00912709922008353.

  PMID: 10392326 BACKGROUND

• 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. doi: 10.5414/cnp57421.

  PMID: 12078944 BACKGROUND

• 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. doi: 10.1097/01.TP.0000058226.39732.32.

  PMID: 12698082 BACKGROUND

• 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.

  PMID: 12736998 BACKGROUND

MeSH Terms

Conditions

Kidney Failure, Chronic; Diabetic Nephropathies; Glomerulonephritis, IGA; Hypertension, Renal; Kidney Diseases; Diabetes Mellitus; Hypertension

Interventions

Mycophenolic Acid

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Diabetes Complications; Endocrine System Diseases; Glomerulonephritis; Nephritis; Autoimmune Diseases; Immune System Diseases; Vascular Diseases; Cardiovascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids

Limitations and Caveats

The treatment of highly sensitized patients on dialysis with single agent therapy of mycophenolate was hampered by gastrointestinal side effects that reduced anticipated maximum tolerated doses and duration of treatment.

Results Point of Contact

• Title: Dr. Connie L. Davis
• Organization: University of Washington

cdavis@u.washington.edu

206-598-7162

Study Officials

• Connie L Davis, MD

  University of Washington

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: March 9, 2007
• First Posted: March 12, 2007
• Study Start: April 1, 2006
• Primary Completion: November 1, 2008
• Study Completion: December 1, 2008
• Last Updated: April 15, 2010
• Results First Posted: March 30, 2010

Record last verified: 2010-04

Locations

US (1)