Acute Optic Neuritis Network: an International Study That Invesitages Subjects With a First-ever Episode of Acute Inflammation of the Optic Nerve
- Conditions
- Demyelinating DiseasesMyelin Oligodendrocyte Glycoprotein Antibody-associated DiseaseOptic NeuritisMultiple SclerosisNeuromyelitis Optica Spectrum Disorder Attack
- Registration Number
- NCT05605951
- Lead Sponsor
- Experimental and Clinical Research Center, a cooperation between the Max Delbrück Center for Molecul
- Brief Summary
The goal of this observational study is to longitudinally investigating subjects with inaugural acute optic neuritis (ON).
The main questions it aims to answer are:
* Does the time to corticosteroid treatment affect the visual outcome at 6 months in subjects with acute multiple sclerosis (MS)-, aquaporin 4-IgG positive (AQP4-IgG+) and myelin-oligodendrocyte-glycoprotein-IgG positive (MOG-IgG+) ON?
* How differ clinical, structural, and laboratory biomarkers in subjects with acute ON, including clinical isolated syndrome (CIS), MS-ON, AQP4-IgG+ON, MOG-IgG+ON and seronegative non-MS-ON? Participants will undergo
* clinical examination, including clinical history, neurovisual and neurological tests
* serum and cerebrospinal fluid examination
* optical coherence tomography (OCT)
* magnetic resonance imaging (MRI)
* assessment of depression, pain, quality of life through validated questionnaires Researchers will compare subjects with MS-ON, AQP4-IgG+ON, MOG-IgG+ON and other ON (CIS, seronegative non-MS-ON) to detect diagnostic and predictive markers for the disease course.
- Detailed Description
The Acute Optic Neuritis Network (ACON) is a global cooperation of currently 26 academic centers longitudinally investigating subjects with inaugural acute optic neuritis (ON). ON often occurs at presentation of multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD) and myelin-oligodendrocyte-glycoprotein (MOG) antibody-associated disease (MOGAD). The recommended treatment of high-dose corticosteroids for ON is based on a North-American study population, which did not address treatment timing, or antibody serostatus. The ACON study is primarily designed to investigate the effect of time to high-dose corticosteroid treatment on 6-month visual outcomes in ON.
All patients presenting within 30 days of inaugural ON will be enrolled. For primary analysis, patients will subsequently be assigned either into the MS-ON, aquaporin-4-IgG positive ON (AQP4-IgG+ON) or MOG-IgG positive ON (MOG-IgG+ON) group and then further sub-stratified according to the number of days from onset of visual loss to high-dose corticosteroids. The primary outcome measure will be high-contrast best-corrected visual acuity (HC-BCVA) at 6 months. Additionally, multimodal data will be collected in subjects with any ON (CIS-ON, MS-ON, AQP4-IgG+ON or MOG-IgG+ON and seronegative non-MS-ON), excluding infectious and granulomatous ON. Secondary outcomes include: optical coherence tomography (OCT) and magnetic resonance imaging (MRI) measurements, serum and cerebrospinal fluid (CSF) biomarkers (AQP4- and MOG-IgG levels; neurofilament; glial fibrillary protein), questionnaires (headache, visual function in daily routine, depression, and quality of life) at presentation, at 6- and 12-months follow-up. Data will be collected from 22 academic hospitals from Africa, Asia, the Middle East, Europe, North America, South America, Australia and Europe. Planned recruitment consists of 100 MS-ON, 50 AQP4-IgG+ON and 50 MOG-IgG+ON.
This prospective, multimodal data collection will assess the potential value of early high-dose corticosteroid treatment, investigate the interrelations between functional impairments and structural changes, and evaluate the diagnostic yield of laboratory biomarkers. This analysis has the ability to substantially improve treatment strategies and accuracy of diagnostic stratification in acute demyelinating ON.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 200
- First-ever acute ON
- Onset of visual symptoms within maximum of 30 days
- Age ≥ 18 years
- Ability to give written informed consent
- Presence of written consent
- MRI contraindication
- Prior demyelinating diagnosis
- Diagnosis of other forms of optic neuropathy (hereditary, granulomatous, infectious, infiltrative, toxic)
- Pregnancy at inclusion
- Relevant other diseases that conflict with study participation according to protocol
- Inability to cooperate
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method to investigate whether MS-ON, AQP4-IgG+ON and MOG-IgG+ON patients treated with early high-dose corticosteroids for visual loss have better visual outcomes and QoL than those with late treatment. Six months follow-up visual acuity
- Secondary Outcome Measures
Name Time Method Diagnostic value of OCT markers for a conversion from acute ON to clinically definite MS. 12 months follow-up OCT markers
Characterization of visual function in daily routine, visual QoL scores and incidence of depression at 1-year follow-up. 12 months follow-up EuroQol 5-Dimension EQ-5D-index
Diagnostic and prognostic value of biomarker levels (NfL, GFAP) and associations with visual pathway damage (MRI- and OCT-based) in the acute stage and during follow-up. 12 months follow-up GFAP (pg/ml)
Characterization of MOG-IgG and AQP4-IgG levels and compartmentalisation (serum vs. CSF, using simultaneous paired samples) and associated risks for subsequent relapses in subjects with AQP4-IgG+ON and MOG-IgG+ON. 12 months follow-up AQP4-IgG ratio
Diagnostic value of OCT markers (e.g. increased pRNFL) for diagnosis of MS, NMOSD, and MOGAD. Six months follow-up pRNFL
Visual and structural outcomes of acute ON in patients treated with high-dose corticosteroid-therapy versus plasmapheresis as first-line treatment. 12 months follow-up MRI lesion score
Prognostic value of OCT markers (e.g. increased pRNFL) for the visual outcome at 1-year follow-up. 12 months follow-up pRNFL
Visual and structural outcomes of MS-ON in patients treated with high-dose corticosteroid-therapy with oral prednisone taper vs. without taper as standard of care. 12 months follow-up RNFL
Diagnostic value of early clinical variables (i.e. visual loss and pain patterns). 12 months follow-up pain intensity
Trial Locations
- Locations (26)
Harvard Medical School
🇺🇸Boston, Massachusetts, United States
Del Rosario University
🇨🇴Bogotá, Colombia
Hospital Aleman
🇦🇷Buenos Aires, Argentina
University of Botswana
🇧🇼Gaborone, Botswana
Hadassah Hebrew University
🇮🇱Jerusalem, Israel
Fukushima Medical University School of Medicine
🇯🇵Fukushima, Japan
University of Colorado School of Medicine
🇺🇸Aurora, Colorado, United States
Department of Ophthalmology, Oftlamo-Sanitas Eye Institute, School of Medicine, Fundación Universitaria Sanitas
🇨🇴Bogotá, Colombia
Nitte University, Karnataka
🇮🇳Mangalore, India
Sackler School of Medicine and Rabin Medical Center
🇮🇱Tel Aviv, Israel
University of Bologna
🇮🇹Bologna, Italy
Federal University of Minas Gerais, Belo Horizonte
🇧🇷Minas Gerais, Brazil
Department of Neurology, Concord Hospital, Faculty of Medicine and Health
🇦🇺Sydney, Australia
Pontificia Universidad Javeriana
🇨🇴Bogotá, Colombia
Department of Neurology, Slagelse, Institute for Health Research, University of Southern Denmark
🇩🇰Odense, Denmark
(MIRCEM) Lyon Civil Hospices, France
🇫🇷Lyon, France
Experimental and Clinical Research Center, Charité - Universitätsmedizin Berlin, Germany, Department of Neurology
🇩🇪Berlin, Germany
Institute for Clinical Neuroimmunology, LMU Clinic of Ludwig-Maximilians Universität in Munich
🇩🇪Munich, Germany
University of Verona
🇮🇹Verona, Italy
National Cancer Center, Seúl University
🇰🇷Seúl, Korea, Republic of
Vall d'Hebron Barcelona Hospital Campus
🇪🇸Barcelona, Spain
Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital
🇬🇧Oxford, United Kingdom
University Hospitals of Birmingham
🇬🇧Birmingham, United Kingdom
University of Barcelona
🇪🇸Barcelona, Spain
University Teaching Hospital in Lusaka
🇿🇲Lusaka, Zambia
Departments of Neurology and Ophthalmology, Mayo Clinic
🇺🇸Rochester, Minnesota, United States