Multiple Sclerosis
Conditions
Keywords
Fingolimod, hepatic adverse events, polymorphism
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
Interventions
DIAGNOSTIC_TESTMeasurement of fingolimod and fingolimod-phosphate concentrations
Measurement of fingolimod and fingolimod-phosphate concentrations before usual drug administration time
GENETICGenetic polymorphism
One blood tube will be taken for genetic testing
Sponsors
University Hospital, Caen
Study design
Observational model
CASE_CONTROL
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CYP4F2 polymorphism frequency in case and control groups | At inclusion | Proportion of CYP4F2 polymorphism in case and control groups |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) |
Countries
France
Contacts
Primary ContactSophie Nguyen, MSc
Outcome results
None listed