Study of the Cellular Diffusion of Tacrolimus Across the Membrane of Mononuclear Cells

NCT03654794 | Completed

• 1 other identifier: LOC/13-11
• Study Type: observational
• Target: 26
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Hemochromatosis

Keywords

Tacrolimus; Pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• Diffusion kinetics of tacrolimus in mononuclear cells

  Determination of tacrolimus in mononuclear cells of subjects Tacrolimus will be assayed by mass spectrometry with a limit of quantification of 10 pg / million cells, sufficient to determine the concentrations in the volunteers' blood.

  At the time of inclusion

Secondary Outcomes (1)

• Determination of the activity of calcineurin in mononuclear cells

  At the time of inclusion

Study Arms (1)

Patients with hemochromatosis

The study is conducted with mononuclear cells obtained from patients undergoing phlebotomy as part of a hemochromatosis treatment. The blood samples will be recovered immediately after their completion. 40 mL of blood will be collected and the mononuclear cells separated using a ficoll gradient. Cell pharmacokinetics of tacrolimus

Biological: Cell pharmacokinetics of tacrolimus

Interventions

Cell pharmacokinetics of tacrolimus BIOLOGICAL

Three levels of tacrolimus will be tested. Each aliquot will be supplemented with an amount of tacrolimus to achieve one of these three levels of concentration. At 0, 5, 15, 30, 60, 120, 240mn, the samples will be separated into 2 aliquots : one dedicated to the determination of tacrolimus in mononuclear cells, the other dedicated to the determination of calcineurin activity. in mononuclear cells.

Also known as: Tacrolimus

Patients with hemochromatosis

Eligibility Criteria

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

Study Population

Patients undergoing phlebotomy as part of a hemochromatosis treatment

You may qualify if:

• adult (age \> 18 years old);
• phlebotomy as part of the maintenance treatment of hemochromatosis;
• having received the information on the protocol and not having indicated his opposition to participate;
• not receiving immunosuppressive therapy;
• not receiving drug treatment that can induce or inhibit the protein ABCB1 (Rifampicin, Carbamazepine, Phenobarbital, Phenytoin, Efavirenz, Amiodarone, azole antifungals, calcium channel blockers).

You may not qualify if:

• participation in another protocol whose procedures are incompatible with the realization of the study;
• adults who are subject to legal protection (protection of justice, guardianship) and persons deprived of their liberty;
• pregnant women.

Sponsors & Collaborators

• Rennes University Hospital: lead

Study Sites (1)

CHU de Rennes

Rennes, 35033, France

Location

Related Publications (2)

• Blanchet B, Hulin A, Duvoux C, Astier A. Determination of serine/threonine protein phosphatase type 2B PP2B in lymphocytes by HPLC. Anal Biochem. 2003 Jan 1;312(1):1-6. doi: 10.1016/s0003-2697(02)00214-2.

  PMID: 12479828 BACKGROUND

• Blanchet B, Hulin A, Ghaleh B, Giraudier S, Jouault H, Astier A. Distribution of calcineurin activity in blood cell fractions and impact of tacrolimus inhibition. Fundam Clin Pharmacol. 2006 Apr;20(2):137-44. doi: 10.1111/j.1472-8206.2006.00399.x.

  PMID: 16573714 BACKGROUND

MeSH Terms

Conditions

Hemochromatosis

Interventions

Tacrolimus

Condition Hierarchy (Ancestors)

Metal Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Iron Overload; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Florian LEMAITRE, MD

  Rennes University Hospital

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 28, 2018
• First Posted: August 31, 2018
• Study Start: October 24, 2013
• Primary Completion: July 6, 2017
• Study Completion: July 6, 2017
• Last Updated: September 4, 2018

Record last verified: 2018-08

Locations

FR (1)