protocolSection identificationModule nctId: NCT06330077, orgStudyIdInfo id: APHP200027, secondaryIdInfos id: 2021-003584-99, type: EUDRACT_NUMBER, briefTitle: Ifenprodil as a ReMyelinating repurpOsed Drug in Multiple Sclerosis, acronym: MODIF-MS, statusModule overallStatus: NOT_YET_RECRUITING, startDateStruct date: 2024-03, primaryCompletionDateStruct date: 2027-03, completionDateStruct date: 2027-06, studyFirstPostDateStruct date: 2024-03-26, lastUpdatePostDateStruct date: 2024-03-26, sponsorCollaboratorsModule leadSponsor name: Assistance Publique - Hôpitaux de Paris, class: OTHER, descriptionModule briefSummary: Multiple sclerosis (MS) is the most frequently acquired demyelinating disease and the first cause of non-traumatic chronic disability in young adults. Major progress has been achieved in the treatment of MS through the development of therapies targeting the adaptative immune system, which drastically reduce the relapse rate, with various efficiency and safety profiles (Ontaneda, 2015). However, these drugs generally fail to prevent disability worsening along the disease course, and we are now assisting to a shift in therapeutic objectives from the development of new immune drugs towards the identification of therapeutic strategies that could prevent neurodegeneration by promoting myelin regeneration (Stangel, 2017; Stankoff, 2016), in order to prevent neurological disability in MS (Irvine and Blakemore, 2008; Patrikios, 2006; Duncan I, 2017, Bodini, 2016).Among the first candidate compounds developed to promote remyelination was the anti Lingo1 antibody, which enhance remyelination (Mi, 2009). Medium and large throughput screening of drug libraries subsequently identified several chemical classes of compounds with strong promyelinating properties, such as the antifongic drug miconazole (Najm, 2015) or the muscarinic antagonist clemastine (Wei, 2014). A recent innovative trial has investigated the effect of clemastine, compared to placebo, in a small sample of subjects (25 patients per group) and showed that clemastine could significantly improve the optic nerve conduction speed which reflecting myelin integrity and functionality (Green, 2017).Our preclinical research has allowed us to identify ifenprodil as a powerful drug to promote myelin repair in vitro and in vivo across species. In parallel our team recently pioneered and optimized a PET imaging approach for quantifying remyelination in the whole brain, that allowed to enhance the sensitivity to detect the myelin repair process, and showed that patients are characterized by heterogeneous profiles of spontaneous remyelination profiles that are closely linked to disability accrual (Bodini, 2016)., conditionsModule conditions: Multiple Sclerosis, conditions: Remitting Relapsing Multiple Sclerosis, designModule studyType: INTERVENTIONAL, phases: PHASE2, designInfo allocation: RANDOMIZED, interventionModel: PARALLEL, primaryPurpose: TREATMENT, maskingInfo masking: SINGLE, whoMasked: PARTICIPANT, enrollmentInfo count: 60, type: ESTIMATED, armsInterventionsModule interventions name: Ifenprodil, interventions name: Placebo, outcomesModule primaryOutcomes measure: Change in P100 latency according to visual evoked potential., secondaryOutcomes measure: Proportion of voxels within white matter lesions classified as remyelinating, secondaryOutcomes measure: Proportion of remyelinating voxels extracted in cortical regions from magnetization transfer imaging (MTR) acquisitions, secondaryOutcomes measure: Change in amplitude of P100 on to visual evoked potential, secondaryOutcomes measure: Change in retinal nerve fibre layer (RNFL) and ganglion cell complex (GCC) thickness on OCT, secondaryOutcomes measure: Change in blood concentration of NfL fragments, secondaryOutcomes measure: Change in the brain atrophy rate, secondaryOutcomes measure: The correlation between the change in the proportion of remyelinating voxels extracted in white matter lesions from [18F]florbetaben PET acquisitions, secondaryOutcomes measure: The comparison of the proportion of remyelinating voxels extracted in white matter lesions from [18F]florbetaben PET acquisitions, secondaryOutcomes measure: Incidence of adverse drug reactions, eligibilityModule sex: ALL, minimumAge: 18 Years, maximumAge: 55 Years, stdAges: ADULT, contactsLocationsModule locations facility: Hôpital Neurologique Pierre WERTHEIMER - HCL, city: Bron, zip: 69677, country: France, contacts name: Françoise DURAND DUBIEF, MD, role: CONTACT, phone: 04 72 35 75 22, email: françoise.durand-dubief@chu-lyon.fr, geoPoint lat: 45.73333, lon: 4.91667, locations facility: Groupe Hospitalier Pitié Salpêtrière - APHP, city: Paris, zip: 75013, country: France, contacts name: Bruno STANKOFF, MD, role: CONTACT, email: bruno.stankoff@aphp.fr, geoPoint lat: 48.85341, lon: 2.3488, hasResults: False