Optimum Immunosuppression in Renal Transplant Recipients.New Onset Diabetes After Transplantation - Full Text View

Sponsor:	Fundación Canaria Rafael Clavijo para la Investigación Biomédica
Information provided by:	Fundación Canaria Rafael Clavijo para la Investigación Biomédica
ClinicalTrials.gov Identifier:	NCT01002339

Purpose

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, Tacrolimus increases 2 times the risk of NODAT as compared to CsA.

Condition	Intervention	Phase
Diabetes Mellitus, Adult-Onset	Drug: Tacrolimus with rapid steroid withdrawal Drug: Tacrolimus with steroids minimization Drug: CsA with steroid minimization	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Prevention
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.

Resource links provided by NLM:

Genetics Home Reference related topics: 6q24-related transient neonatal diabetes mellitus

MedlinePlus related topics: Kidney Transplantation

Drug Information available for: Tacrolimus anhydrous Tacrolimus

U.S. FDA Resources

Further study details as provided by Fundación Canaria Rafael Clavijo para la Investigación Biomédica:

Primary Outcome Measures:

The primary efficacy variable is the proportion of patients with NODAT or glucose intolerance at 1 year defined by the ADA criteria including an oral glucose tolerance test [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

rate of acute rejection [ Time Frame: 1 year ] [ Designated as safety issue: No ]
renal function [ Time Frame: 1 year ] [ Designated as safety issue: No ]
proteinuria [ Time Frame: 1 year ] [ Designated as safety issue: No ]
blood pressure and number of antihypertensive drugs [ Time Frame: 1 year ] [ Designated as safety issue: No ]
lipidic profile and use of lipid lowering drugs (stains) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
changes of carotid intima-media thickness over time [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment:	210
Study Start Date:	February 2010
Estimated Study Completion Date:	October 2012
Estimated Primary Completion Date:	October 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Tacrolimus with rapid steroid withdrawal	Drug: Tacrolimus with rapid steroid withdrawal Tacrolimus 0.15 mg/Kg/day to achieve target trough levels of 8-12 ng/ml for the first month, and MMF 2 gr/day; steroids: 0.5 gr of Methylprednisolone (MP) intraoperatively and 125 mg on the first day, followed by oral doses of prednisone rapidly tapered from 30 mg/day to complete discontinuation by postoperative day 7
Experimental: Tacrolimus with steroids minimization	Drug: Tacrolimus with steroids minimization Tacrolimus 0.15 mg/Kg/day to achieve target trough levels of 8-12 ng/ml for the first month, and MMF 2 gr/day; steroids: 0.5 gr of MP intraoperatively and 60 mg day 1; followed by oral doses of prednisone and gradual tapering to complete discontinuation over 6 months.
Active Comparator: CsA with steroid minimization	Drug: CsA with steroid minimization CsA 5 mg/Kg/day to achieve target trough of 125-175 ng/ml the first month, and similar pattern with MMF and steroids as group 2

Detailed Description:

New onset diabetes alter 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

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Primary renal transplant recipients in chronic haemodialysis program
No prior history of diabetes mellitus before transplant
Recipient age over 45
Absence of Immunologic risk defined by the investigator criterion and PRA< 50%
Absence of severe infection, and active hepatitis C or B
Efficient contraception in women during the study
At least one of the following pretransplant criteria:
- Serum Triglycerides ≥200 mg/dl
- Body mass index (BMI)>27 and Serum Triglycerides >150 mg/dl
- HDL-cholesterol<40 mg/dl for men or <50 mg/dl for women and Serum Triglycerides >150 mg/dl

Exclusion Criteria:

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01002339

Contacts

Contact: Armando Torres, PhD

+34 922678115

atorres@ull.es

Locations

Spain
Antonio Osuna	Recruiting
Granada, Andalucía, Spain, 18014
Contact: Antonio Osuna, M.D.
Principal Investigator: Antonio Osuna, M.D.
María Dolores Burgos	Recruiting
Málaga, Andalucía, Spain, 29010
Contact: María Dolores Burgos, M.D.
Principal Investigator: María Dolores Burgos, M.D.
José María Baltar	Recruiting
Oviedo, Asturias, Spain, 33006
Contact: Juan María Baltar, M.D.
Principal Investigator: Juan María Baltar, M.D.
Carlos Gómez Alamillo	Recruiting
Santander, Cantabria, Spain, 39008
Contact: Carlos Gómez Alamillo, M.D.
Principal Investigator: Carlos Gómez Alamillo, M.D.
Francisco Moreso	Recruiting
Barcelona, Cataluña, Spain, 08035
Contact: Francisco Moreso, M.D.
Principal Investigator: Francisco Moreso, M.D.
Juan Manuel Díaz	Recruiting
Barcelona, Cataluña, Spain, 08025
Contact: Juan Manuel Díaz, M.D.
Principal Investigator: Juan Manuel Díaz, M.D.
Francisco Valdés	Recruiting
La Coruña, Galicia, Spain, 15006
Contact: Francisco Valdés, M.D.
Principal Investigator: Francisco Valdés, M.D.
Armando Torres Ramírez	Recruiting
La Laguna, S/C de Tenerife, Spain, 38320
Contact: Armando Torres Ramírez, PhD +34 922678573 atorres@ull.es
Principal Investigator: Armando Torres Ramírez, PhD
Roberto Gallego	Recruiting
Las Palmas de Gran Canaria, Spain, 35010
Contact: Roberto Gallego, MD
Principal Investigator: Roberto Gallego, M.D.
Ana María Fernández Rodríguez	Not yet recruiting
Madrid, Spain, 28034
Contact: Ana Mª Fernández Rodríguez, MD
Principal Investigator: Ana Mª Fernández Rodríguez, MD
Luis Pallardo	Recruiting
Valencia, Spain, 46017
Contact: Luis Pallardo, M.D.
Principal Investigator: Luis Pallardo, M.D.

Sponsors and Collaborators

Fundación Canaria Rafael Clavijo para la Investigación Biomédica

Investigators

Study Director:

Armando Torres, PhD

Fundación Canaria para la Investigación Biomédica Rafael Clavijo

More Information

Publications:

Delgado P, Diaz JM, Silva I, Osorio JM, Osuna A, Bayés B, Lauzurica R, Arellano E, Campistol JM, Dominguez R, Gómez-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. Epub 2008 Mar 5.

Porrini E, Gomez MD, Alvarez A, Cobo M, Gonzalez-Posada JM, Perez L, Hortal L, García JJ, Dolores Checa M, Morales A, Hernández 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. Epub 2007 Mar 29.

Alvarez A, Fernandez J, Porrini E, Delgado P, Pitti S, Vega MJ, González-Posada JM, Rodríguez A, Pérez L, Marrero D, Luis D, Velázquez S, Hernández 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.

Hernández D, Miquel R, Porrini E, Fernández A, González-Posada JM, Hortal L, Checa MD, Rodríguez A, García 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.

Porrini E, Delgado P, Alvarez A, Cobo M, Pérez L, González-Posada JM, Hortal L, Gallego R, García JJ, Checa M, Morales A, Salido E, Hernández 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. Epub 2007 Nov 19.

Porrini E, Moreno JM, Osuna A, Benitez R, Lampreabe I, Diaz JM, Silva I, Domínguez 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.

Bayés B, Moreso F, Benítez R, Torres A, Díaz JM, Granada ML, Lauzurica R, Pastor MC, Teixidó J. [Post-transplant diabetes mellitus depending on the pre-transplant dialysis technique] Nefrologia. 2008;28 Suppl 6:97-102. Spanish.

Porrini E, Bayes B, Diaz JM, Ibernon M, Benitez R, Domínguez 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.

Responsible Party:	Dr. Armando Torres Ramírez, Fundación Rafael Clavijo para la Investigación Biomédica
ClinicalTrials.gov Identifier:	NCT01002339 History of Changes
Other Study ID Numbers:	FundacionRC
Study First Received:	October 26, 2009
Last Updated:	May 5, 2011
Health Authority:	Spain: Spanish Agency of Medicines

Additional relevant MeSH terms:

Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases

Tacrolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 09, 2012