Clinical Trials Logo
  1. Home
  2. Hemochromatosis
  3. NCT03654794

Study of the Cellular Diffusion of Tacrolimus Across the Membrane of Mononuclear Cells — DIFF-TAC  

Hemochromatosis Clinical Trial

Official title:
Study of the Cellular Diffusion of Tacrolimus Across the Membrane of Mononuclear Cells

Clinical Trial Summary

Pharmacokinetics of tacrolimus are highly variable and may result in graft rejection (underdosing) or toxicity (overdosing).

The risk of transplant rejection and the toxicity of tacrolimus can be reduced by pharmacological therapeutic monitoring of the molecule, based on the measurement of residual blood concentrations. Nevertheless, some patients are victims of rejections or toxic signs even though their blood concentrations are in the therapeutic target.

The aim of the study is to describe the pharmacokinetics of tacrolimus diffusion in mononuclear cells as well as the kinetics of effect of the drug on its target protein

Clinical Trial Description

Factors responsible for pharmacokinetic variability of tacrolimus are multiple: compliance, diet, drug interactions and also genetic polymorphism of cytochrome P450 3A5 (CYP 3A5) and efflux protein ABCB1 (P-glycoprotein, P-gp).

The mechanism of action of tacrolimus is based on inhibition of calcineurin in T cells. Therefore, tacrolimus intra-lymphocyte concentration may be a finer marker of the risk of transplant rejection or toxicity. The degree of inhibition of calcineurin in the T lymphocyte could also be a pharmacodynamic marker more relevant than the blood concentration. The hypothesis that the ABCB1 efflux pump is the main factor limiting the diffusion of tacrolimus into mononuclear cells is advanced.

The diffusion of tacrolimus into mononuclear cells and the impact of the ABCB1 efflux pump on this diffusion have not been studied to date. The effect kinetics of the drug on calcineurin in mononuclear cells is also unknown.

The aim of the study is to describe the pharmacokinetics of tacrolimus diffusion in mononuclear cells as well as the kinetics of effect of the drug on its target protein: calcineurin in the presence or absence of an efflux pump inhibitor ABCB1 at room temperature and at 4 ° C (in order to inhibit all transport proteins) from blood obtained from 18 patients undergoing bleeding as part of maintenance treatment for hemochromatosis. ;

Study Design

Related Conditions & MeSH terms

Clinical Trial Details
NCT number NCT03654794
Study type Observational
Source Rennes University Hospital
Contact
Status Completed
Phase
Start date October 24, 2013
Completion date July 6, 2017
View Details
See also
  Status Clinical Trial Phase
Completed NCT00199628 - Research Network for Neonatal Diseases Induced by Tissular Fetomaternal Alloimmunization
Terminated NCT00122980 - Stroke With Transfusions Changing to Hydroxyurea Phase 3
Completed NCT00202436 - Haemochromatosis:Phlebotomy Versus Erythrocytapheresis Therapy Phase 3
Withdrawn NCT01892644 - Treatment of Iron Overload With Deferasirox (Exjade) in Hereditary Hemochromatosis and Myelodysplastic Syndrome Phase 2
Not yet recruiting NCT01524757 - Proton Pump Inhibitors in the Prevention of Iron Reaccumulation in Patient With Hereditary Hemochromatosis N/A
Completed NCT00349453 - Study Using Deferiprone Alone or in Combination With Desferrioxamine in Iron Overloaded Transfusion-dependent Patients Phase 2
Recruiting NCT03743272 - Repeatability and Reproducibility of Multiparametric MRI
Recruiting NCT06137079 - "Iron Overload and Endocrinological Diseases"
Completed NCT00712738 - Oral Nifedipine to Treat Iron Overload Phase 1
Completed NCT00001455 - Iron Overload in African Americans N/A
Completed NCT00006312 - Hemochromatosis--Genetic Prevalence and Penetrance N/A
Completed NCT00005559 - Statistical Basis for Hemochromatosis Screening N/A
Recruiting NCT00509652 - Erythrocyte Apheresis Versus Phlebotomy in Hemochromatosis N/A
Completed NCT00350662 - Study With Deferiprone and/or Desferrioxamine in Iron Overloaded Patients Phase 3
Completed NCT00005541 - Hemochromatosis and Iron Overload Screening Study (HEIRS) N/A
Completed NCT00000595 - Evaluation of Subcutaneous Desferrioxamine as Treatment for Transfusional Hemochromatosis Phase 2
Completed NCT04631718 - MRI QSM Imaging for Iron Overload
Active, not recruiting NCT00007150 - Treatment of Hemochromatosis Phase 2
Completed NCT00587535 - Evaluation of a New MR Pulse Sequence to Quantify Liver Iron Concentration N/A
Enrolling by invitation NCT02025543 - Confounder-Corrected Quantitative MRI Biomarker of Hepatic Iron Content