Měsíční monitorování plazmatického NfL u léčené relaps-remitující roztroušené sklerózy k detekci perzistující infra-klinické aktivity onemocnění (MoMo-NfL)
Měsíční monitorování plazmatického NfL u léčených pacientů s RRMS k detekci přetrvávající infraklinické aktivity onemocnění
Reference MRI scan is recommended 6 months after treatment onset in patients with multiple sclerosis (MS), and follow-up scans at 12 months later to monitor subclinical activity. When monitoring treatment response in patients treated with disease modifying treatments (DMTs), the measurement of new or enlarging T2/FLAIR hyperintense lesions (NELs) is the preferred MRI method supplemented by contrast-enhancing lesions (CELs) for monitoring treatment response. However, some studies have suggested the deposition of gadolinium-based contrast agents in the basal ganglia and dentate nucleus of patients who underwent serial MRI acquisitions. Although significant clinical consequences of these deposits have not been demonstrated, further studies are required to better understand the potential long-term biological and clinical effects of gadolinium administration. To circumvent this potential risk, several recommendations suggested avoiding unnecessary use of gadolinium for follow-up scans. New sequences are also developed to replace gadolinium injection for the detection of active lesions. Moreover, MRI remains costly and time-consuming. In addition, systematic yearly MRI monitoring is not adapted to detect silent active lesions. This can delay identification of treatment failure and increase the risk of relapses and disability worsening, especially in the context of escalation therapy.
Therefore, biological markers could allow more frequent analysis of disease activity and detect treatment failure earlier than classical clinical and MRI monitoring. Their use would greatly help clinicians to switch for high efficacy treatments (HET) and avoid potential relapses.
Measurement of a structural axonal protein, neurofilament, in serum or plasma has shown promise as a marker of neuroaxonal injury and a measure of treatment response. In MS, cerebrospinal fluid (CSF) neurofilament-light chain (NfL) is also increased and is positively associated with MRI lesion load and disability scores and is a marker of treatment response.
WThe study authors hypothesize that monthly plasma neurofilament-light chain (pNfL) monitoring can sensitively highlight subclinical (radiological disease activity) RDA by performing early MRI scans to confirm EDA and lead to timely treatment escalation.
The main objective of this study is to compare the time to EDA in both arms (monthly pNfL monitoring vs. standard care with regular MRI scans), in patients with EDA.
Přehled studie
Postavení
Intervence / Léčba
Typ studie
Zápis (Odhadovaný)
Fáze
- Nelze použít
Kontakty a umístění
Studijní kontakt
- Jméno: Eric Thouvenot
- Telefonní číslo: 04 66 68 32 61
- E-mail: eric.thouvenot@chu-nimes.fr
Studijní místa
-
-
-
Montpellier, Francie, 34295
- Nábor
- CHU de Montpellier - Hôpital Guy de Chauliac
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Kontakt:
- Xavier AYRIGNAC, PU-PH
- Telefonní číslo: 33+ 04 67 33 67 33
- E-mail: x-ayrignac@chu-montpellier.fr
-
Nantes, Francie, 44000
- Zatím nenabíráme
- CHU de Nantes
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Kontakt:
- David LAPLAUD, PU-PH
- Telefonní číslo: 33+02 40 08 33 33
- E-mail: david.laplaud@chu-nantes.fr
-
Nice, Francie
- Nábor
- CHU de Nice
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Kontakt:
- Christine LEBRUN FRENAY, Pr.
- E-mail: lebrun-frenay.c@chu-nice.fr
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Nîmes, Francie
- Nábor
- CHU de Nîmes
-
Kontakt:
- Anissa Megzari
- Telefonní číslo: 04.66.68.42.36
- E-mail: drc@chu-nimes.fr
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Paris, Francie, 75013
- Nábor
- AP-HP, Hôpital de la Pitié Salpêtrière
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Kontakt:
- Elisabeth MAILLART, PU-PH
- Telefonní číslo: 33+ 01 42 17 60 60
- E-mail: elisabeth.maillart@aphp.fr
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Rennes, Francie
- Zatím nenabíráme
- CHU de Rennes
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Kontakt:
- Laure MICHEL, PU-PH
- Telefonní číslo: 33 + 02 99 28 43 21
- E-mail: laure.michel@chu-rennes.fr
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-
Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
Inclusion Criteria:
- Patient with RRMS according to 2024 McDonald's criteria.
- Less than 10 years from disease onset.
- Active RRMS (EDA) observed during the last 24 months: relapse and/or NELs and/or CELs as compared to a previous MRI performed within 24 months (± 3 months).
- Current MET (IFN, GA, TE, fumarates) for less than 24 months.
- Standard MRI follow-up scan performed less than 90 days before inclusion.
- Clinically stable disease for at least 30 days.
- Patients included in observational studies and cohorts (OFSEP, PROMISE …) will be eligible for inclusion in MoMo-NfL.
- For women with reproductive potential: negative pregnancy test at the time of inclusion and use of an effective method to avoid pregnancy for the duration of the trial.
- Patients able to adhere to the study visit schedule.
- Patient must have signed and given the consent.
- Patient affiliated or beneficiary of a health insurance plan.
Exclusion Criteria:
- Pregnant or breastfeeding woman.
- Patient unable to perform brain and/or spinal cord MRI scans.
- Patient not willing to perform monthly blood punctures.
- Patient treated with HET (S1P agonists, natalizumab, ocrelizumab, ofatumumab, rituximab, alemtuzumab, cladribine, mitoxantrone).
- Patient with a relapse within 6 months before inclusion.
- Patient with CELs within 3 months before inclusion.
- Patient with progressive MS.
- Patient unable to sign the consent.
- It is impossible to correctly inform the patient.
- Patient already participating in therapeutic research or in an exclusion period. The exclusion period corresponds to five half-lives (t1/2) of the experimental drug.
- Patient under judicial protection, or is an adult under guardianship.
- Female patients who are pregnant or breastfeeding or of reproductive potential who are not willing to employ effective birth control for the duration of the trial.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Jiný
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
|
Žádný zásah: Standardní péče
|
|
|
Experimentální: Skupina pro monitorování pNfL
|
Monthly pNfL monitoring from blood samples. In case of >50% pNfL increase as compared to the mean of the 2 previous measures, an unscheduled visit with brain and spinal cord MRI will be scheduled |
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Time to evidence of disease activity between groups
Časové okno: week 48
|
As assessed by new relapse and/or occurrence of NELs and/or CELs on a follow-up MRI scan |
week 48
|
|
Time to evidence of disease activity between groups
Časové okno: week 96
|
As assessed by new relapse and/or occurrence of NELs and/or CELs on a follow-up MRI scan |
week 96
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Proportion of CELs between groups
Časové okno: week 48
|
percent of active (contrast-enhancing) lesion |
week 48
|
|
Proportion of CELs between groups
Časové okno: week 96
|
percent of active (contrast-enhancing) lesion |
week 96
|
|
Rate of clinical relapses between groups
Časové okno: week 48
|
percentage patients experiencing relapse |
week 48
|
|
Rate of clinical relapses between groups
Časové okno: week 96
|
percentage patients experiencing relapse |
week 96
|
|
Time to switch to high efficacy treatments
Časové okno: week 48
|
Days |
week 48
|
|
Time to switch to high efficacy treatments
Časové okno: week 96
|
Days |
week 96
|
|
Proportion of patients switching to high efficacy treatments between groups
Časové okno: week 48
|
Percentage |
week 48
|
|
Proportion of patients switching to high efficacy treatments between groups
Časové okno: week 96
|
Percentage |
week 96
|
|
Change in pNfL levels in patients experiencing relapse with active MRI in experimental group
Časové okno: Upon experiencing relapse (maximum week 96)
|
pg/mL; measured using Lumipulse® G NfL Blood |
Upon experiencing relapse (maximum week 96)
|
|
Change in pNfL levels in patients experiencing acute clinical event in experimental group
Časové okno: Upon experiencing an acute clinical event (maximum week 96)
|
pg/mL; measured using Lumipulse® G NfL Blood |
Upon experiencing an acute clinical event (maximum week 96)
|
|
Change in pNfL levels in patients experiencing radiological disease activity without clinical symptoms in experimental group
Časové okno: Upon experiencing radiological disease activity (maximum week 96)
|
pg/mL; measured using Lumipulse® G NfL Blood |
Upon experiencing radiological disease activity (maximum week 96)
|
|
Change in pNfL levels in patients switching to high efficacy treatments
Časové okno: Upon evidence of disease activity (maximum week 96)
|
pg/mL; measured using Lumipulse® G NfL Blood |
Upon evidence of disease activity (maximum week 96)
|
Další výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
To estimate the best threshold of pNfL increase (last measure as compared to the mean of 2 previous measures) with best accuracy to detect evidence of disease activity
Časové okno: week 96
|
pNfL levels in pg/mL |
week 96
|
|
Time to evidence of disease activity using optimized threshold in experimental group
Časové okno: week 96
|
Months |
week 96
|
|
Correlation between basal pNfL fluctuations in patients with no evidence of disease activity and brain health questionnaire score
Časové okno: week 96
|
Brain-Q |
week 96
|
|
Description of adverse events
Časové okno: week 96
|
Descriptive |
week 96
|
|
Level of disability
Časové okno: Baseline (Day 0)
|
EDSS (Extanded Disability Status Scale) score, range: 0.0-10 |
Baseline (Day 0)
|
|
Level of disability
Časové okno: Week 48
|
EDSS (Extanded Disability Status Scale) score, range: 0.0-10 |
Week 48
|
|
Level of disability
Časové okno: week 96
|
EDSS (Extanded Disability Status Scale) score, range: 0.0-10 |
week 96
|
|
Information processing speed impairment
Časové okno: Baseline (Day 0)
|
CSCT (Computerized Speed Cognitive Test): score and standard deviation |
Baseline (Day 0)
|
|
Information processing speed impairment
Časové okno: week 48
|
CSCT (Computerized Speed Cognitive Test): score and standard deviation |
week 48
|
|
Information processing speed impairment
Časové okno: week 96
|
CSCT (Computerized Speed Cognitive Test): score and standard deviation |
week 96
|
|
Manual dexterity
Časové okno: Baseline (Day 0)
|
NHPT (Nine Hole Peg Test): time (seconds) |
Baseline (Day 0)
|
|
Manual dexterity
Časové okno: week 48
|
NHPT (Nine Hole Peg Test): time (seconds) |
week 48
|
|
Manual dexterity
Časové okno: week 96
|
NHPT (Nine Hole Peg Test): time (seconds) |
week 96
|
|
Walking function
Časové okno: Baseline (Day 0)
|
T25FW (Timed 25-Foot Walk); time (seconds) |
Baseline (Day 0)
|
|
Walking function
Časové okno: week 48
|
T25FW (Timed 25-Foot Walk); time (seconds) |
week 48
|
|
Walking function
Časové okno: week 96
|
T25FW (Timed 25-Foot Walk); time (seconds) |
week 96
|
|
Patient-reported change in status
Časové okno: Baseline (Day 0)
|
PGIC (Patient Global Impression of Change scale): score (7 points Likert scale) |
Baseline (Day 0)
|
|
Patient-reported change in status
Časové okno: Week 48
|
PGIC (Patient Global Impression of Change scale): score (7 points Likert scale) |
Week 48
|
|
Patient-reported change in status
Časové okno: week 96
|
PGIC (Patient Global Impression of Change scale): score (7 points Likert scale) |
week 96
|
|
Patient-reported quality of life
Časové okno: Baseline (Day 0)
|
EQ-5D-5L score (0-100) |
Baseline (Day 0)
|
|
Patient-reported quality of life
Časové okno: week 48
|
EQ-5D-5L score (0-100) |
week 48
|
|
Patient-reported quality of life
Časové okno: week 96
|
EQ-5D-5L score (0-100) |
week 96
|
Spolupracovníci a vyšetřovatelé
Vyšetřovatelé
- Vrchní vyšetřovatel: Eric Thouvenot, Centre Hospitalier Universitaire de Nīmes
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
Další identifikační čísla studie
- FINEX/2025/ET-01
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