Clinical trial NCT01195194: Selection of Immunosuppression in Kidney Transplant Recipients Depending on Pre-transplant Donor-specific T-cell Reactivity.
Official title: Pilot Study of Selection of Either Calcineurin Inhibitor(CNI)-Based or CNI-free Immunosuppressive Regimen Depending on the Result of Pre-transplantation Donor-specific T-cell Reactivity Measured by Enzyme-linked Immunosorbent Spot(ELISPOT) in Standard-risk Kidney Recipients.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Disorder Related to Renal Transplantation
Keywords: T-cell lymphocyte allo-recognition
CNI-free immunosuppressive regimen
Enzyme-linked immunospot (ELISPOT)
Lead sponsor: Hospital Universitari de Bellvitge
Sponsor class: OTHER
Collaborators: name: Carlos III Health Institute
First posted: 2010-09-06
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective is to assess if low pre-transplantation donor specific T-cell reactive patients measured by Enzyme-linked immunosorbent spot (ELISPOT)assay can be safely managed with Calcineurin inhibitor(CNI)-free Sirolimus(SRL)-based immunosuppression.

Detailed description: Non randomized, pilot, prospective, open-label trial.

Eligibility criteria: Inclusion Criteria:

1. Age of donor and recipient between 18 and 65 years.
2. End-stage renal disease and scheduled to receive a primary or secondary renal allograft from a cadaveric, a living-unrelated, or a living-related donor. Patients scheduled for a second transplant must have maintained their primary graft for at least 6 months after transplantation, with the exception of graft failure due to technical reasons.
3. Panel reactive antibody (PRA) ≤ 20%, with negative standard cross-match.
4. Women of childbearing potential must have a negative serum pregnancy test before randomization.
5. Women of childbearing potential must agree to use a medically acceptable method of contraception throughout the treatment period and for 3 months following discontinuation of assigned treatment.
6. Signed and dated informed consent prior to transplantation.

Exclusion Criteria:

1. Multiple organ transplants
2. Recipients of adult or pediatric en bloc kidney transplants or dual transplantation or non-heart beating donors.
3. Evidence of active systemic or localized major infection.
4. Evidence of infiltrate, cavitation, or consolidation on chest x-ray obtained during the screening/baseline evaluation.
5. Use of any investigational drug or treatment up to 4 weeks prior to transplantation.
6. Treatment with voriconazole, ketoconazole, itraconazole, fluconazole, clotrimazole, astemizole, pimozide, terfenadine, erythromycin, clarithromycin, telithromycin, troleandomycin, rifampin, rifabutin, or St. John's Wort that is not discontinued prior to randomization.
7. Treatment with aminoglycosides, amphotericin B, cisplatin, cisapride, metoclopramide, cimetidine, bromocriptine, danazol, or other drugs associated with renal dysfunction that are not discontinued prior to randomization.
8. Subjects with a screening/baseline total white blood cell count \< 2,000/mm3 or absolute neutrophil count (ANC) \< 500, platelet count \< 100,000/mm3.
9. Fasting triglycerides \> 400 mg/dL (\> 4.6 mmol/L) or fasting total cholesterol \> 300 mg/dL (\> 7.8 mmol/L) despite optimal lipid-lowering therapy.
10. History of malignancy within 2 years of enrollment (except for adequately treated basal cell or squamous cell carcinoma of the skin).
11. Auto-immune diseases inactive immunosuppressive treatment ( 3 months prior to inclusion).
12. Patient with psychiatric disorders that could be non-compliance for the treatment.
13. Non Caucasian patients.
14. Active peptic ulcers that could produce intestinal absorption disorders.
15. Subjects who are known to be human immunodeficiency virus(HIV) or hepatitis B virus (HBV) positive. Patients with hepatitis C virus (HCV) positive should be excluded if polymerase chain reaction (PCR) positive or transaminates values are ≥2 upper normal value (UNV).
16. Diabetic patients.
17. Body mass index higher than 30 Kg/m2.

Primary outcomes:
measure: Percentage of biopsy-confirmed acute rejection episodes
timeFrame: 6 months
Secondary outcomes:
measure: Percentage of steroid-sensitive acute rejection episodes
timeFrame: 6 months
measure: Percentage of acute rejection episodes requiring treatment with antilymphocyte antibodies.
timeFrame: 6 months
measure: Renal function estimated by Modification of Diet in Renal Disease (MDRD) formula.
timeFrame: 12 months
measure: Proteinuria measured in g/day
timeFrame: 6 months
measure: Histology at month 6 protocol kidney allograft biopsy
timeFrame: 6 months
measure: Percentage of patients with negative ELISPOT
timeFrame: 6 months
measure: Percentage of patients in group A requiring CNI introduction.
timeFrame: 24 months
measure: Percentage of patients presenting adverse events requiring study withdrawal
timeFrame: 24 months
measure: Percentage of biopsy-confirmed acute rejection episodes
timeFrame: 12 months
measure: Percentage of steroid-sensitive acute rejections rejection episodes
timeFrame: 12 months
measure: Percentage of acute rejection episodes requiring treatment with antilymphocyte antibodies
timeFrame: 12 months
measure: Proteinuria measured in g/day
timeFrame: 12 months
measure: Percentage of patients with negative ELISPOT
timeFrame: 12 months
Other outcomes:
Locations:
city: L'Hospitalet de Llobregat
country: Spain
facility: Nephrology Department. Hospital de Bellvitge
state: Barcelone
city: Barcelona
country: Spain
facility: Nephrology Department. Hospital Vall d'Hebró
Study officials:
affiliation: Nephrology Department. Hospital de Bellvitge. Spain
name: Josep M Grinyó, PhD MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bestard O, Cruzado JM, Mestre M, Caldes A, Bas J, Carrera M, Torras J, Rama I, Moreso F, Seron D, Grinyo JM. Achieving donor-specific hyporesponsiveness is associated with FOXP3+ regulatory T cell recruitment in human renal allograft infiltrates. J Immunol. 2007 Oct 1;179(7):4901-9. doi: 10.4049/jimmunol.179.7.4901.
citation: Bestard O, Crespo E, Stein M, Lucia M, Roelen DL, de Vaal YJ, Hernandez-Fuentes MP, Chatenoud L, Wood KJ, Claas FH, Cruzado JM, Grinyo JM, Volk HD, Reinke P. Cross-validation of IFN-gamma Elispot assay for measuring alloreactive memory/effector T cell responses in renal transplant recipients. Am J Transplant. 2013 Jul;13(7):1880-90. doi: 10.1111/ajt.12285. Epub 2013 Jun 13.
citation: Bestard O, Cruzado JM, Lucia M, Crespo E, Casis L, Sawitzki B, Vogt K, Cantarell C, Torras J, Melilli E, Mast R, Martinez-Castelao A, Goma M, Reinke P, Volk HD, Grinyo JM. Prospective assessment of antidonor cellular alloreactivity is a tool for guidance of immunosuppression in kidney transplantation. Kidney Int. 2013 Dec;84(6):1226-36. doi: 10.1038/ki.2013.236. Epub 2013 Jun 19.