Ignite Creation Date:
2025-12-25 @ 1:32 AM
Ignite Modification Date:
2026-02-26 @ 12:36 AM
Study NCT ID:
NCT03654794
Status:
COMPLETED
Last Update Posted:
2018-09-04
First Post:
2018-08-28
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Study of the Cellular Diffusion of Tacrolimus Across the Membrane of Mononuclear Cells
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D006432', 'term': 'Hemochromatosis'}], 'ancestors': [{'id': 'D008664', 'term': 'Metal Metabolism, Inborn Errors'}, {'id': 'D008661', 'term': 'Metabolism, Inborn Errors'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}, {'id': 'D019190', 'term': 'Iron Overload'}, {'id': 'D019189', 'term': 'Iron Metabolism Disorders'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D016559', 'term': 'Tacrolimus'}], 'ancestors': [{'id': 'D018942', 'term': 'Macrolides'}, {'id': 'D007783', 'term': 'Lactones'}, {'id': 'D009930', 'term': 'Organic Chemicals'}]}}, 'protocolSection': {'designModule': {'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 26}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2013-10-24', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2018-08', 'completionDateStruct': {'date': '2017-07-06', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2018-08-31', 'studyFirstSubmitDate': '2018-08-28', 'studyFirstSubmitQcDate': '2018-08-29', 'lastUpdatePostDateStruct': {'date': '2018-09-04', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2018-08-31', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2017-07-06', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Diffusion kinetics of tacrolimus in mononuclear cells', 'timeFrame': 'At the time of inclusion', 'description': "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."}], 'secondaryOutcomes': [{'measure': 'Determination of the activity of calcineurin in mononuclear cells', 'timeFrame': 'At the time of inclusion', 'description': 'These determinations will be carried out by Dr. Benoit Blanchet according to a validated and published method (cf references Blanchet et al, 2003; Blanchet et al, 2006).\n\nThe method is based on high pressure liquid chromatography (HPLC coupled) with spectrophotometric detection.'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Tacrolimus', 'Pharmacokinetics'], 'conditions': ['Hemochromatosis']}, 'referencesModule': {'references': [{'pmid': '12479828', 'type': 'BACKGROUND', 'citation': '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': '16573714', 'type': 'BACKGROUND', 'citation': '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.'}]}, 'descriptionModule': {'briefSummary': 'Pharmacokinetics of tacrolimus are highly variable and may result in graft rejection (underdosing) or toxicity (overdosing).\n\nThe 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.\n\nThe 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', 'detailedDescription': '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).\n\nThe 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.\n\nThe 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.\n\nThe 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'Patients undergoing phlebotomy as part of a hemochromatosis treatment', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* adult (age \\> 18 years old);\n* phlebotomy as part of the maintenance treatment of hemochromatosis;\n* having received the information on the protocol and not having indicated his opposition to participate;\n* not receiving immunosuppressive therapy;\n* not receiving drug treatment that can induce or inhibit the protein ABCB1 (Rifampicin, Carbamazepine, Phenobarbital, Phenytoin, Efavirenz, Amiodarone, azole antifungals, calcium channel blockers).\n\nExclusion Criteria:\n\n* participation in another protocol whose procedures are incompatible with the realization of the study;\n* adults who are subject to legal protection (protection of justice, guardianship) and persons deprived of their liberty;\n* pregnant women.'}, 'identificationModule': {'nctId': 'NCT03654794', 'acronym': 'DIFF-TAC', 'briefTitle': 'Study of the Cellular Diffusion of Tacrolimus Across the Membrane of Mononuclear Cells', 'organization': {'class': 'OTHER', 'fullName': 'Rennes University Hospital'}, 'officialTitle': 'Study of the Cellular Diffusion of Tacrolimus Across the Membrane of Mononuclear Cells', 'orgStudyIdInfo': {'id': 'LOC/13-11'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'Patients with hemochromatosis', 'description': 'The study is conducted with mononuclear cells obtained from patients undergoing phlebotomy as part of a hemochromatosis treatment.\n\nThe 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.\n\nCell pharmacokinetics of tacrolimus', 'interventionNames': ['Biological: Cell pharmacokinetics of tacrolimus']}], 'interventions': [{'name': 'Cell pharmacokinetics of tacrolimus', 'type': 'BIOLOGICAL', 'otherNames': ['Tacrolimus'], 'description': '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.\n\nAt 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.', 'armGroupLabels': ['Patients with hemochromatosis']}]}, 'contactsLocationsModule': {'locations': [{'zip': '35033', 'city': 'Rennes', 'country': 'France', 'facility': 'CHU de Rennes', 'geoPoint': {'lat': 48.11109, 'lon': -1.67431}}], 'overallOfficials': [{'name': 'Florian LEMAITRE, MD', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Rennes University Hospital'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Rennes University Hospital', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}