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

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ClinicalTrials.gov Identifier: NCT05516303
Recruitment Status : Recruiting
First Posted : August 25, 2022
Last Update Posted : August 25, 2022
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment
Multiple Sclerosis Genetic: Genetic polymorphism Diagnostic Test: Measurement of fingolimod and fingolimod-phosphate concentrations

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

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Study Type : Observational
Estimated Enrollment : 65 participants
Observational Model: Case-Control
Time Perspective: Retrospective
Official Title: Pharmacogenetic Investigation of Susceptibility to Liver Toxicity in Patients With Multiple Sclerosis Treated With Fingolimod
Actual Study Start Date : June 7, 2022
Estimated Primary Completion Date : October 31, 2022
Estimated Study Completion Date : October 31, 2022

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. CYP4F2 polymorphism frequency in case and control groups [ Time Frame: At inclusion ]
    Proportion of CYP4F2 polymorphism in case and control groups


Secondary Outcome Measures :
  1. 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)

  2. 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)


Biospecimen Retention:   Samples With DNA
Blood


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05516303


Contacts
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Contact: Sophie Nguyen, MSc +33(0)231065127 nguyen-s@chu-caen.fr

Locations
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France
Caen University Hospital Recruiting
Caen, France, 14000
Contact: Sophie Nguyen, Msc       nguyen-s@chu-caen.fr   
Sponsors and Collaborators
University Hospital, Caen
Investigators
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Principal Investigator: Gilles Defer, MD University Hospital, Caen
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Responsible Party: University Hospital, Caen
ClinicalTrials.gov Identifier: NCT05516303    
Other Study ID Numbers: 22-0041
First Posted: August 25, 2022    Key Record Dates
Last Update Posted: August 25, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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
Keywords provided by University Hospital, Caen:
Fingolimod
hepatic adverse events
polymorphism
Additional relevant MeSH terms:
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Multiple Sclerosis
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Fingolimod Hydrochloride
Sphingosine 1 Phosphate Receptor Modulators
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs