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

• Conditions: Multiple Sclerosis

• Registration Number: NCT05516303
• Lead Sponsor: University Hospital, Caen

Brief 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.

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

Study Timeline

• Status Verified: 2022-05
• Study Start: 2022-06-07
• Study First Submitted: 2022-06-10
• Study First Submitted QC: 2022-08-23
• Last Update Submitted: 2022-08-23
• Study First Posted: 2022-08-25
• Last Update Posted: 2022-08-25
• Primary Completion: 2022-10-31
• Study Completion: 2022-10-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 65

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
CYP4F2 polymorphism frequency in case and control groups	At inclusion	Proportion of CYP4F2 polymorphism in case and control groups

Secondary Outcome Measures

Name	Time	Method
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)

Trial Locations

Locations (1)

Caen University Hospital; 🇫🇷 Caen, France