Pharmacogenetics of Liver Toxicity in Patients With Multiple Sclerosis Treated With Fingolimod

NCT05516303 — Unknown, 65 participants, University Hospital, Caen

ClinicalTrials Daily · Areas · Conditions · Drugs · Sponsors ·

Pharmacogenetic Investigation of Susceptibility to Liver Toxicity in Patients With Multiple Sclerosis Treated With Fingolimod

Registry	NCT05516303
Status	Unknown
Study type	Observational
Enrollment	65 (Estimated)
Sponsor	University Hospital, Caen (Other)
Conditions	Multiple Sclerosis
Interventions	Genetic polymorphism, Measurement of fingolimod and fingolimod-phosphate concentrations (Genetic, diagnostic test)
Dates	start 2022-06-07, primary completion 2022-10-31 (estimated), completion 2022-10-31 (estimated), first posted 2022-08-25, last updated 2022-08-25
Locations	1 site in France

-Summary

To investigate whether polymorphic differences can be identified between Multiple Sclerosis patients developing elevated liver enzymes (defined as ALT, AST, GGT or bilirubinemia levels five above the upper normal limit on at least one) compared to those not developing elevated liver enzymes after exposure to fingolimod for multiple sclerosis.

Expand all sections · Collapse all

+Detailed description

PURPOSE: To investigate whether polymorphic differences can be identified between Multiple sclerosis (MS) patients treated by fingolimod who had liver enzymes elevation compared to those who do not.

OBJECTIVE: To determine whether elevated liver enzyme tests (ALT, AST, GGT or bilirubinemia above the upper limit of normal) in MS patients treated with fingolimod is associated with genetic polymorphisms.

METHOD OF RECRUITMENT:

Patients will be identified through a clinic database and chart reviews. A phone call will be made to determine interest. Upon a follow-up neurological consultation, consent into study will be sought.

PROCEDURES:

Blood samples will be collected for genetic analyses, fingolimod and fingolimod-phosphate quantification and a questionnaire will be administered

+Arms and interventions

Arm	Type	Interventions	Description
Case		Genetic: Genetic polymorphism; Diagnostic Test: Measurement of fingolimod and fingolimod-phosphate concentrations	MS patients treated with fingolimod who experienced liver enzymes elevation
Control		Genetic: Genetic polymorphism; Diagnostic Test: Measurement of fingolimod and fingolimod-phosphate concentrations	MS patients treated with fingolimod not experiencing elevated liver enzymes

Genetic polymorphism (Genetic): One blood tube will be taken for genetic testing
Measurement of fingolimod and fingolimod-phosphate concentrations (Diagnostic test): Measurement of fingolimod and fingolimod-phosphate concentrations before usual drug administration time

+Outcome measures

Primary outcomes

CYP4F2 polymorphism frequency in case and control groups [At inclusion]: Proportion of CYP4F2 polymorphism in case and control groups

Secondary outcomes

Fingolimod concentrations in case and control groups [At inclusion]: Trough concentration of fingolimod in blood samples determined by liquid chromatography-tandem mass spectrometry (LC-MS)
Fingolimod-phosphate concentrations in case and control groups [At inclusion]: Trough concentration of fingolimod-phosphate in blood samples determined by liquid chromatography-tandem mass spectrometry (LC-MS)

+Eligibility

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Adults (> 18 years)
* Have a definite Multiple Sclerosis with a relapsing-remitting course (McDonald criteria)
* Treated with fingolimod
* Have given consent and signed an informed consent form

Exclusion Criteria:

* an elevated liver test result on baseline before starting fingolimod treatment
* presence of a viral, hereditary or auto-immune liver pathology
* Time of fingolimod exposure lower than three months
* Woman currently pregnant or breastfeeding

+Locations (1)

Facility	City	Country	Status
Caen University Hospital	Caen	France	Recruiting

+Investigators

Gilles Defer, MD, Principal investigator, University Hospital, Caen