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

August 23, 2022 updated by: University Hospital, Caen

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Observational

Enrollment (Anticipated)

65

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Multiple sclerosis (MS) patients attending out-patient neurological consultations in Caen University Hospital, with a relapsing-remitting disease course, and prescribed fingolimod as a disease-modifying drug for MS.

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Retrospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Case
MS patients treated with fingolimod who experienced liver enzymes elevation
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
Control
MS patients treated with fingolimod not experiencing elevated liver enzymes
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
CYP4F2 polymorphism frequency in case and control groups
Time Frame: At inclusion
Proportion of CYP4F2 polymorphism in case and control groups
At inclusion

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Caen

Investigators

  • Principal Investigator: Gilles Defer, MD, University Hospital, Caen

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 7, 2022

Primary Completion (Anticipated)

October 31, 2022

Study Completion (Anticipated)

October 31, 2022

Study Registration Dates

First Submitted

June 10, 2022

First Submitted That Met QC Criteria

August 23, 2022

First Posted (Actual)

August 25, 2022

Study Record Updates

Last Update Posted (Actual)

August 25, 2022

Last Update Submitted That Met QC Criteria

August 23, 2022

Last Verified

May 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 22-0041

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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