Clinical trial NCT01002339: Optimum Immunosuppression in Renal Transplant Recipients.New Onset Diabetes After Transplantation
Official title: Optimum Immunosuppression in Renal Transplant Recipients at High Risk of Developing New Onset Diabetes After Transplantation: A Multicenter, Prospective, Controlled and Randomized Trial.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Diabetes Mellitus, Adult-Onset
Lead sponsor: Fundación Canaria Rafael Clavijo para la Investigación Biomédica
Sponsor class: OTHER
First posted: 2009-10-27
Enrollment: 134
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: New onset diabetes after renal transplantation (NODAT) is a common and severe complication negatively influencing graft and patient survival. Cyclosporine (CsA) and Tacrolimus are the basis of modern immunosuppression. Tacrolimus is superior to CsA in terms of acute rejection and graft function. However, Tacrolimus increases 2 times the risk of NODAT as compared to CsA.

Detailed description: New onset diabetes after renal transplantation (NODAT) is a common and severe complication negatively influencing graft and patient survival. CsA and Tacrolimus are the basis of modern immunosuppression. Tacrolimus is superior to CsA in terms of acute rejection and graft function. However, increases 2 times the risk of NODAT as compared to CsA. Objectives: a) To compare the incidence of NODAT and glucose intolerance with 3 different regimes: Tacrolimus with rapid steroid withdrawal; Tacrolimus with steroids minimization; and CsA with steroid minimization; b) To compare acute rejection rate, renal function and graft and patient survival between different regimes; and c) to investigate the influence of different regimes on subclinical atheromatosis. A total of 210 patients will be randomized. The primary efficacy variable will be NODAT or glucose intolerance at 1 year; secondary efficacy variables will be acute rejection, renal function, and changes of carotid intima-media thickness over time.

Eligibility criteria: Inclusion Criteria:

* Primary renal transplant recipients with end stage renal disease
* No prior history of diabetes mellitus before transplant
* Absence of Immunologic risk defined by the investigator criterion and Panel Reactive Antibody (PRA) \< 50%
* Absence of severe infection and hepatitis C or B infection
* Efficient contraception in women during the study

Additionally must meet one of these "Metabolic Criteria

* Recipient age \>or =60 or
* Recipient age between 45 and 59 years and at least one of the following metabolic criteria: Prior to transplantation Triglycerides (TGS) \>200mg/dl or the combination of a body mass index (BMI)\> 27 and Triglycerides\>150 mg/dl or the combination of HDL-cholesterol\<40 mg/dl for men or \<50 mg/dl for women and Triglycerides \>150 mg/dl.

Exclusion Criteria:

* Patients with type I or II diabetes prior to transplantation defined by the American Diabetes Association (ADA) criteria
* Recipient age under 45
* Patients receiving a second renal transplant
* Patients with high immunological risk or PRA (panel reactive antibody level) \>or =50%
* Severe infection or hepatitis C or B infection.
* Dual renal transplant or double transplant with any other organ.

Primary outcomes:
measure: Primary Outcome Measure "New Onset Diabetes After Renal Transplantation" (NODAT)
timeFrame: 1 year
measure: Patients Treated With Insulin or Oral Antidiabetic Drugs
timeFrame: 1 year
measure: Primary Outcome Measure (Glucose Intolerance)
timeFrame: 1 year
Secondary outcomes:
measure: Rejection
timeFrame: 1 year
measure: Renal Function
timeFrame: 1 year
measure: Proteinuria
timeFrame: 1 year
measure: Blood Pressure
timeFrame: 1 year
measure: Blood Pressure
timeFrame: 1 year
measure: Number of Antihypertensive Drugs Patients Reported Taking.
timeFrame: 1 year
measure: Lipidic Profile (Triglycerides)
timeFrame: 1 year
measure: Lipidic Profile (Cholesterol)
timeFrame: 1 year
measure: Lipidic Profile (HDL-c)
timeFrame: 1 year
measure: Lipidic Profile (LDL-c)
timeFrame: 1 year
measure: Percentage of Patients Using Statins
timeFrame: 1 year
measure: Changes of Carotid Intima-media Thickness Over Time
timeFrame: 1 year
measure: Percentage of Patients Using Acetylsalicylic Acid (ASA)
timeFrame: 1 year
Other outcomes:
Locations:
city: Granada
country: Spain
facility: Antonio Osuna
state: Andalucía
city: Málaga
country: Spain
facility: Domingo Hernández
state: Andalucía
city: Oviedo
country: Spain
facility: Carmen Díaz Corte
state: Asturias
city: Santander
country: Spain
facility: Carlos Gómez Alamillo
state: Cantabria
city: Barcelona
country: Spain
facility: Juan Manuel Díaz
state: Cataluña
city: Barcelona
country: Spain
facility: Francisco Moreso
state: Cataluña
city: La Coruña
country: Spain
facility: Francisco Valdés
state: Galicia
city: La Laguna
country: Spain
facility: Armando Torres Ramírez
state: S/C De Tenerife
city: Las Palmas de Gran Canaria
country: Spain
facility: Roberto Gallego
city: Valencia
country: Spain
facility: Luis Pallardo
Study officials:
affiliation: Fundación Canaria para la Investigación Biomédica Rafael Clavijo
name: Armando Torres, PhD
role: STUDY_DIRECTOR
References:
citation: Porrini E, Gomez MD, Alvarez A, Cobo M, Gonzalez-Posada JM, Perez L, Hortal L, Garcia JJ, Dolores Checa M, Morales A, Hernandez D, Torres A. Glycated haemoglobin levels are related to chronic subclinical inflammation in renal transplant recipients without pre-existing or new onset diabetes. Nephrol Dial Transplant. 2007 Jul;22(7):1994-9. doi: 10.1093/ndt/gfm067. Epub 2007 Mar 29.
citation: Alvarez A, Fernandez J, Porrini E, Delgado P, Pitti S, Vega MJ, Gonzalez-Posada JM, Rodriguez A, Perez L, Marrero D, Luis D, Velazquez S, Hernandez D, Salido E, Torres A. Carotid atheromatosis in nondiabetic renal transplant recipients: the role of prediabetic glucose homeostasis alterations. Transplantation. 2007 Oct 15;84(7):870-5. doi: 10.1097/01.tp.0000284462.70064.ae.
citation: Hernandez D, Miquel R, Porrini E, Fernandez A, Gonzalez-Posada JM, Hortal L, Checa MD, Rodriguez A, Garcia JJ, Rufino M, Torres A. Randomized controlled study comparing reduced calcineurin inhibitors exposure versus standard cyclosporine-based immunosuppression. Transplantation. 2007 Sep 27;84(6):706-14. doi: 10.1097/01.tp.0000282872.17024.b7.
citation: Porrini E, Delgado P, Alvarez A, Cobo M, Perez L, Gonzalez-Posada JM, Hortal L, Gallego R, Garcia JJ, Checa M, Morales A, Salido E, Hernandez D, Torres A. The combined effect of pre-transplant triglyceride levels and the type of calcineurin inhibitor in predicting the risk of new onset diabetes after renal transplantation. Nephrol Dial Transplant. 2008 Apr;23(4):1436-41. doi: 10.1093/ndt/gfm762. Epub 2007 Nov 19.
citation: Porrini E, Moreno JM, Osuna A, Benitez R, Lampreabe I, Diaz JM, Silva I, Dominguez R, Gonzalez-Cotorruelo J, Bayes B, Lauzurica R, Ibernon M, Moreso F, Delgado P, Torres A. Prediabetes in patients receiving tacrolimus in the first year after kidney transplantation: a prospective and multicenter study. Transplantation. 2008 Apr 27;85(8):1133-8. doi: 10.1097/TP.0b013e31816b16bd.
citation: Bayes B, Moreso F, Benitez R, Torres A, Diaz JM, Granada ML, Lauzurica R, Pastor MC, Teixido J. [Post-transplant diabetes mellitus depending on the pre-transplant dialysis technique]. Nefrologia. 2008;28 Suppl 6:97-102. Spanish.
citation: Porrini E, Bayes B, Diaz JM, Ibernon M, Benitez R, Dominguez R, Moreno JM, Delgado P, Lauzurica R, Silva I, Moreso F, Lampreabe I, Arias M, Osuna A, Torres A. Hyperinsulinemia and hyperfiltration in renal transplantation. Transplantation. 2009 Jan 27;87(2):274-9. doi: 10.1097/TP.0b013e318191a7d5.
citation: Porrini EL, Diaz JM, Moreso F, Delgado Mallen PI, Silva Torres I, Ibernon M, Bayes-Genis B, Benitez-Ruiz R, Lampreabe I, Lauzurrica R, Osorio JM, Osuna A, Dominguez-Rollan R, Ruiz JC, Jimenez-Sosa A, Gonzalez-Rinne A, Marrero-Miranda D, Macia M, Garcia J, Torres A. Clinical evolution of post-transplant diabetes mellitus. Nephrol Dial Transplant. 2016 Mar;31(3):495-505. doi: 10.1093/ndt/gfv368. Epub 2015 Nov 3.
citation: Rodriguez-Rodriguez AE, Trinanes J, Porrini E, Velazquez-Garcia S, Fumero C, Vega-Prieto MJ, Diez-Fuentes ML, Luis Lima S, Salido E, Torres A. Glucose homeostasis changes and pancreatic beta-cell proliferation after switching to cyclosporin in tacrolimus-induced diabetes mellitus. Nefrologia. 2015;35(3):264-72. doi: 10.1016/j.nefro.2015.05.007. Epub 2015 Jun 27. English, Spanish.
citation: Rodriguez-Rodriguez AE, Trinanes J, Velazquez-Garcia S, Porrini E, Vega Prieto MJ, Diez Fuentes ML, Arevalo M, Salido Ruiz E, Torres A. The higher diabetogenic risk of tacrolimus depends on pre-existing insulin resistance. A study in obese and lean Zucker rats. Am J Transplant. 2013 Jul;13(7):1665-75. doi: 10.1111/ajt.12236. Epub 2013 May 7.
citation: Delgado P, Diaz JM, Silva I, Osorio JM, Osuna A, Bayes B, Lauzurica R, Arellano E, Campistol JM, Dominguez R, Gomez-Alamillo C, Ibernon M, Moreso F, Benitez R, Lampreave I, Porrini E, Torres A. Unmasking glucose metabolism alterations in stable renal transplant recipients: a multicenter study. Clin J Am Soc Nephrol. 2008 May;3(3):808-13. doi: 10.2215/CJN.04921107. Epub 2008 Mar 5.