Optimum Immunosuppression in Renal Transplant Recipients.New Onset Diabetes After Transplantation

Diabetes Mellitus, Adult-Onset Clinical Trial

— 01-DMPT  

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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01002339
• Other study ID #: FundacionRC
• Status: Terminated
• Phase: Phase 4
• First received: October 26, 2009
• Last updated: March 19, 2015
• Start date: February 2010
• Est. completion date: June 2015

Study information

• Verified date: October 2014
• Source: Fundación Canaria Rafael Clavijo para la Investigación Biomédica
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 145
• Est. completion date: June 2015
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 active hepatitis C or B

• Efficient contraception in women during the study

Additionally must meet one of these "Metabolic Criteria

• Recipient age >or =60

• Recipient age between 45 and 59 years over one of two 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 Serum Triglycerides >150 mg/dl,

or

HbA1c between 5.5-6.5%, the combination of HbA1c >= 5.2% and TG>=150 mg/dl, or the combination of HbA1c >= 5.2% y IMC>27

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 active hepatitis C or B.

• Dual renal transplant or double transplant with any other organ.

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Diabetes Mellitus, Adult-Onset
• Diabetes Mellitus, Type 2

Intervention

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
• 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.
• CsA with steroid minimization
CsA 5 mg/Kg/day to achieve target trough of 150-200 ng/ml the first month, and similar pattern with MMF and steroids as group 2

Locations

Country	Name	City	State
Spain	Francisco Moreso	Barcelona	Cataluña
Spain	Juan Manuel Díaz	Barcelona	Cataluña
Spain	Antonio Osuna	Granada	Andalucía
Spain	Francisco Valdés	La Coruña	Galicia
Spain	Armando Torres Ramírez	La Laguna	S/C de Tenerife
Spain	Roberto Gallego	Las Palmas de Gran Canaria
Spain	María Dolores Burgos	Málaga	Andalucía
Spain	Minerva Rodríguez García	Oviedo	Asturias
Spain	Emilio Rodrigo Calabia	Santander	Cantabria
Spain	Luis Pallardo	Valencia

Sponsors (1)

Lead Sponsor	Collaborator
Armando Torres Ramírez

Country where clinical trial is conducted

Spain, 

References & Publications (8)

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. — View Citation

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. — View Citation

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 tran — View Citation

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. — View Citation

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. doi: 10.1097/TP.0b013e318191a7d5. — View Citation

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. — View Citation

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. — View Citation

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. doi: 10.1097/TP.0b013e31816b16bd. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		1 year	Yes
Secondary	rate of acute rejection		1 year	No
Secondary	renal function		1 year	No
Secondary	proteinuria		1 year	No
Secondary	blood pressure and number of antihypertensive drugs		1 year	No
Secondary	lipidic profile and use of lipid lowering drugs (stains)		1 year	No
Secondary	changes of carotid intima-media thickness over time		1 year	No