search
Back to results

Optimum Immunosuppression in Renal Transplant Recipients.New Onset Diabetes After Transplantation (01-DMPT)

Primary Purpose

Diabetes Mellitus, Adult-Onset

Status
Terminated
Phase
Phase 4
Locations
Spain
Study Type
Interventional
Intervention
Tacrolimus with rapid steroid withdrawal
Tacrolimus with steroids minimization
CsA with steroid minimization
Sponsored by
Armando Torres Ramírez
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Diabetes Mellitus, Adult-Onset

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Antonio Osuna
  • Domingo Hernández
  • Carmen Díaz Corte
  • Carlos Gómez Alamillo
  • Juan Manuel Díaz
  • Francisco Moreso
  • Francisco Valdés
  • Armando Torres Ramírez
  • Roberto Gallego
  • Luis Pallardo

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Experimental

Arm Label

Tacrolimus with rapid steroid withdrawal

Tacrolimus with steroids minimization

CsA with steroid minimization

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

Primary Outcome Measure "New Onset Diabetes After Renal Transplantation" (NODAT)
American Diabetes Association criteria (ADA) including an oral glucose tolerance test.
Patients Treated With Insulin or Oral Antidiabetic Drugs
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.

Secondary Outcome Measures

Rejection
Biopsy proven acute rejection. Measured variable: Rate of Biopsy proven acute rejection.
Renal Function
Estimated Glomerular Filtration Rate (ml/min/1.73 m^2)
Proteinuria
Blood Pressure
Systolic pressure (mmHg)
Blood Pressure
Diastolic pressure (mmHg)
Number of Antihypertensive Drugs Patients Reported Taking.
Lipidic Profile (Triglycerides)
Lipidic Profile (Cholesterol)
Lipidic Profile (total cholesterol)
Lipidic Profile (HDL-c)
Lipidic Profile (LDL-c)
Percentage of Patients Using Statins
Changes of Carotid Intima-media Thickness Over Time
absolute difference between carotid intima-media thickness at study end versus baseline.
Percentage of Patients Using Acetylsalicylic Acid (ASA)

Full Information

First Posted
October 26, 2009
Last Updated
March 23, 2017
Sponsor
Armando Torres Ramírez
search

1. Study Identification

Unique Protocol Identification Number
NCT01002339
Brief Title
Optimum Immunosuppression in Renal Transplant Recipients.New Onset Diabetes After Transplantation
Acronym
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.
Study Type
Interventional

2. Study Status

Record Verification Date
March 2017
Overall Recruitment Status
Terminated
Why Stopped
Terminated: higher rate of acute rejection in the Cyclosporin A group
Study Start Date
February 2010 (undefined)
Primary Completion Date
February 2014 (Actual)
Study Completion Date
June 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Armando Torres Ramírez

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Adult-Onset

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
134 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Tacrolimus with rapid steroid withdrawal
Arm Type
Experimental
Arm Description
Basiliximab induction. Tacrolimus plus Mycophenolate mofetil (MMF), and corticosteroids with rapid withdrawal after one week.
Arm Title
Tacrolimus with steroids minimization
Arm Type
Active Comparator
Arm Description
Basiliximab induction.Tacrolimus plus Mycophenolate mofetil (MMF) and low-dose corticosteroids for 6 months with subsequent removal
Arm Title
CsA with steroid minimization
Arm Type
Experimental
Arm Description
Basiliximab induction. Ciclosporin A (CsA) plus Mycophenolate mofetil (MMF) and low-dose corticosteroids for 6 months with subsequent removal
Intervention Type
Drug
Intervention Name(s)
Tacrolimus with rapid steroid withdrawal
Other Intervention Name(s)
Simulect; Dacortin; Prograf/Advagraf; Cellcept/Myfortic.
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Tacrolimus with steroids minimization
Other Intervention Name(s)
Simulect; Dacortin; Prograf/Advagraf; Cellcept/Myfortic.
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
CsA with steroid minimization
Other Intervention Name(s)
Simulect; Dacortin; Sandimmun Neoral; Cellcept/Myfortic.
Intervention Description
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
Primary Outcome Measure Information:
Title
Primary Outcome Measure "New Onset Diabetes After Renal Transplantation" (NODAT)
Description
American Diabetes Association criteria (ADA) including an oral glucose tolerance test.
Time Frame
1 year
Title
Patients Treated With Insulin or Oral Antidiabetic Drugs
Time Frame
1 year
Title
Primary Outcome Measure (Glucose Intolerance)
Description
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.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Rejection
Description
Biopsy proven acute rejection. Measured variable: Rate of Biopsy proven acute rejection.
Time Frame
1 year
Title
Renal Function
Description
Estimated Glomerular Filtration Rate (ml/min/1.73 m^2)
Time Frame
1 year
Title
Proteinuria
Time Frame
1 year
Title
Blood Pressure
Description
Systolic pressure (mmHg)
Time Frame
1 year
Title
Blood Pressure
Description
Diastolic pressure (mmHg)
Time Frame
1 year
Title
Number of Antihypertensive Drugs Patients Reported Taking.
Time Frame
1 year
Title
Lipidic Profile (Triglycerides)
Time Frame
1 year
Title
Lipidic Profile (Cholesterol)
Description
Lipidic Profile (total cholesterol)
Time Frame
1 year
Title
Lipidic Profile (HDL-c)
Time Frame
1 year
Title
Lipidic Profile (LDL-c)
Time Frame
1 year
Title
Percentage of Patients Using Statins
Time Frame
1 year
Title
Changes of Carotid Intima-media Thickness Over Time
Description
absolute difference between carotid intima-media thickness at study end versus baseline.
Time Frame
1 year
Title
Percentage of Patients Using Acetylsalicylic Acid (ASA)
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Armando Torres, PhD
Organizational Affiliation
Fundación Canaria para la Investigación Biomédica Rafael Clavijo
Official's Role
Study Director
Facility Information:
Facility Name
Antonio Osuna
City
Granada
State/Province
Andalucía
ZIP/Postal Code
18014
Country
Spain
Facility Name
Domingo Hernández
City
Málaga
State/Province
Andalucía
ZIP/Postal Code
29010
Country
Spain
Facility Name
Carmen Díaz Corte
City
Oviedo
State/Province
Asturias
ZIP/Postal Code
33006
Country
Spain
Facility Name
Carlos Gómez Alamillo
City
Santander
State/Province
Cantabria
ZIP/Postal Code
39008
Country
Spain
Facility Name
Juan Manuel Díaz
City
Barcelona
State/Province
Cataluña
ZIP/Postal Code
08025
Country
Spain
Facility Name
Francisco Moreso
City
Barcelona
State/Province
Cataluña
ZIP/Postal Code
08035
Country
Spain
Facility Name
Francisco Valdés
City
La Coruña
State/Province
Galicia
ZIP/Postal Code
15006
Country
Spain
Facility Name
Armando Torres Ramírez
City
La Laguna
State/Province
S/C de Tenerife
ZIP/Postal Code
38320
Country
Spain
Facility Name
Roberto Gallego
City
Las Palmas de Gran Canaria
ZIP/Postal Code
35010
Country
Spain
Facility Name
Luis Pallardo
City
Valencia
ZIP/Postal Code
46017
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
17395658
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.
Results Reference
background
PubMed Identifier
17984840
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.
Results Reference
background
PubMed Identifier
17893603
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.
Results Reference
background
PubMed Identifier
18029372
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.
Results Reference
background
PubMed Identifier
18431233
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.
Results Reference
background
PubMed Identifier
18957019
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.
Results Reference
background
PubMed Identifier
19155984
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.
Results Reference
background
PubMed Identifier
26538615
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.
Results Reference
background
PubMed Identifier
26299169
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.
Results Reference
background
PubMed Identifier
23651473
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.
Results Reference
background
PubMed Identifier
18322043
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.
Results Reference
result

Learn more about this trial

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

We'll reach out to this number within 24 hrs