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

Multiple Sclerosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05516303
• Other study ID #: 22-0041
• Status: Recruiting
• Start date: June 7, 2022
• Est. completion date: October 31, 2022

Study information

• Verified date: May 2022
• Source: University Hospital, Caen
• Contact: Sophie Nguyen, MSc
• Phone: +33(0)231065127
• Email: nguyen-s[@]chu-caen.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 65
• Est. completion date: October 31, 2022
• Est. primary completion date: October 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

Genetic:
• Genetic polymorphism
One blood tube will be taken for genetic testing

Diagnostic Test:
• Measurement of fingolimod and fingolimod-phosphate concentrations
Measurement of fingolimod and fingolimod-phosphate concentrations before usual drug administration time

Locations

Country	Name	City	State
France	Caen University Hospital	Caen

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Caen

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CYP4F2 polymorphism frequency in case and control groups	Proportion of CYP4F2 polymorphism in case and control groups	At inclusion
Secondary	Fingolimod concentrations in case and control groups	Trough concentration of fingolimod in blood samples determined by liquid chromatography-tandem mass spectrometry (LC-MS)	At inclusion
Secondary	Fingolimod-phosphate concentrations in case and control groups	Trough concentration of fingolimod-phosphate in blood samples determined by liquid chromatography-tandem mass spectrometry (LC-MS)	At inclusion