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

NCT01002339 | Terminated Phase 4 Results

• 1 other identifier: FundacionRC
• Study Type: interventional
• Target: 134
• Locations: 1 country
• Sites: 10

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.

Conditions

Diabetes Mellitus, Adult-Onset

Outcome Measures

Primary Outcomes (3)

• Primary Outcome Measure "New Onset Diabetes After Renal Transplantation" (NODAT)

  American Diabetes Association criteria (ADA) including an oral glucose tolerance test.

  1 year

• Patients Treated With Insulin or Oral Antidiabetic Drugs

  1 year

• Primary Outcome Measure (Glucose Intolerance)

  Glycemia \>=140 and \<200 mg/dl, 2 hours after a standard oral glucose tolerance test. Measured values: glucose intolerance at 1 year defined by ADA criteria.

  1 year

Secondary Outcomes (13)

• Rejection

  1 year

• Renal Function

  1 year

• Proteinuria

  1 year

• Blood Pressure

  1 year

• Blood Pressure

  1 year

Study Arms (3)

Tacrolimus with rapid steroid withdrawal

EXPERIMENTAL

Basiliximab induction. Tacrolimus plus Mycophenolate mofetil (MMF), and corticosteroids with rapid withdrawal after one week.

Drug: Tacrolimus with rapid steroid withdrawal

Tacrolimus with steroids minimization

ACTIVE COMPARATOR

Basiliximab induction.Tacrolimus plus Mycophenolate mofetil (MMF) and low-dose corticosteroids for 6 months with subsequent removal

Drug: Tacrolimus with steroids minimization

CsA with steroid minimization

EXPERIMENTAL

Basiliximab induction. Ciclosporin A (CsA) plus Mycophenolate mofetil (MMF) and low-dose corticosteroids for 6 months with subsequent removal

Drug: CsA with steroid minimization

Interventions

Tacrolimus with rapid steroid withdrawal DRUG

* Basiliximab induction (4 mg i.v., days 0 and 4). * Corticosteroids: 0.5 gr of i.v. 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: 0.15 mg/Kg/day to achieve target trough levels of 8-12 ng/ml for the first month and then 5-8 ng/ml. * Mycophenolate mofetil 1 gr b.i.d. for the first month and then 500 mg b.i.d.

Also known as: Simulect; Dacortin; Prograf/Advagraf; Cellcept/Myfortic.

Tacrolimus with rapid steroid withdrawal

Tacrolimus with steroids minimization DRUG

* Basiliximab induction (4 mg i.v., days 0 an 4) * Corticosteroids: 0.5 gr of i.v. MP intraoperatively and 60 mg on the first day, followed by oral doses of prednisone starting with 0.3 mg/Kg/day, and gradual weekly tapering to complete discontinuation over 6 months. * Tacrolimus 0.15 mg/Kg/day to achieve target trough levels of 8-12 ng/ml for the first month and then 5-8 ng/ml. * Mycophenolate mofetil 1 gr b.i.d. for the first month and then 500 mg b.i.d.

Also known as: Simulect; Dacortin; Prograf/Advagraf; Cellcept/Myfortic.

Tacrolimus with steroids minimization

CsA with steroid minimization DRUG

* Basiliximab induction (4 mg i.v., days 0 an 4) * Corticosteroids: 0.5 gr of i.v. MP intraoperatively and 60 mg on the first day, followed by oral doses of prednisone starting with 0.3 mg/Kg/day, and gradual weekly tapering to complete discontinuation over 6 months. * CsA 5 mg/Kg/day to achieve target trough of 150-200 ng/ml the first month and then 100-150 ng/ml. * Mycophenolate mofetil 1 gr b.i.d

Also known as: Simulect; Dacortin; Sandimmun Neoral; Cellcept/Myfortic.

CsA with steroid minimization

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Armando Torres Ramírez: lead

Study Sites (10)

Antonio Osuna

Granada, Andalusia, 18014, Spain

Location

Domingo Hernández

Málaga, Andalusia, 29010, Spain

Location

Carlos Gómez Alamillo

Santander, Cantabria, 39008, Spain

Location

Juan Manuel Díaz

Barcelona, Catalonia, 08025, Spain

Location

Francisco Moreso

Barcelona, Catalonia, 08035, Spain

Location

Francisco Valdés

A Coruña, Galicia, 15006, Spain

Location

Carmen Díaz Corte

Oviedo, Principality of Asturias, 33006, Spain

Location

Armando Torres Ramírez

San Cristóbal de La Laguna, S/C de Tenerife, 38320, Spain

Location

Roberto Gallego

Las Palmas de Gran Canaria, 35010, Spain

Location

Luis Pallardo

Valencia, 46017, Spain

Location

Related Publications (11)

• 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.

  PMID: 17395658 BACKGROUND

• 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.

  PMID: 17984840 BACKGROUND

• 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.

  PMID: 17893603 BACKGROUND

• 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.

  PMID: 18029372 BACKGROUND

• 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.

  PMID: 18431233 BACKGROUND

• 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.

  PMID: 18957019 BACKGROUND

• 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.

  PMID: 19155984 BACKGROUND

• 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.

  PMID: 26538615 BACKGROUND

• 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.

  PMID: 26299169 BACKGROUND

• 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.

  PMID: 23651473 BACKGROUND

• 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.

  PMID: 18322043 RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Tacrolimus; Basiliximab; Prednisone; Cyclosporine; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Peptides; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Results Point of Contact

• Title: Dr. Armando Torres Ramírez
• Organization: Hospital Universitario de Canarias. Universidad de La Laguna. Spain

atorres@ull.es

+34630989515

Study Officials

• Armando Torres, PhD

  Fundación Canaria para la Investigación Biomédica Rafael Clavijo

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: PhD

Study Record Dates

• First Submitted: October 26, 2009
• First Posted: October 27, 2009
• Study Start: February 1, 2010
• Primary Completion: February 1, 2014
• Study Completion: June 1, 2015
• Last Updated: October 22, 2024
• Results First Posted: August 3, 2016

Record last verified: 2024-09

Locations

ES (10)