Clinical trial NCT05605951: Acute Optic Neuritis Network: an International Study That Invesitages Subjects With a First-ever Episode of Acute Inflammation of the Optic Nerve
Official title: The Acute Optic Neuritis Network (ACON): a Non-interventional Prospective Multicenter Study on Diagnosis and Treatment of Acute Optic Neuritis
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Demyelinating Diseases
Multiple Sclerosis
Neuromyelitis Optica Spectrum Disorder Attack
Myelin Oligodendrocyte Glycoprotein Antibody-associated Disease
Optic Neuritis
Lead sponsor: Experimental and Clinical Research Center, a cooperation between the Max Delbrück Center for Molecul
Sponsor class: OTHER
First posted: 2022-11-04
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: At least 300 patients with acute ON will be screened for study eligibility. We will include only inaugural ON patients. Subjects presenting for the first time with isolated ON or ON with additional demyelinating syndromes, e.g. myelitis or acute disseminated encephalomyelitis (ADEM) occurring within 30 days of the acute ON will be included. Patients with prior soft symptoms which can retrospectively be considered to be a demyelinating manifestation will be included, excluding patients with a prior demyelinating diagnosis. The prevalence of MS-, AQP4-IgG+ON and MOG-IgG+ON differs in each of the participating centers. For primary analysis, we collect data from subjects with MS-ON, AQP4-IgG+ON and MOG-IgG+ON. For secondary analysis, multimodal data will be collected in subjects with any demyelinating ON (CIS-ON, MS-ON, AQP4-IgG+ON or MOG-IgG+ON and seronegative non-MS-ON). We expect between 30-50% will be ineligible due to the rigorous exclusion criteria.

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: 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.
timeFrame: Six months follow-up
Secondary outcomes:
measure: Visual and structural outcomes of acute ON in patients treated with high-dose corticosteroid-therapy versus plasmapheresis as first-line treatment.
timeFrame: Six months follow-up
measure: Visual and structural outcomes of acute ON in patients treated with high-dose corticosteroid-therapy versus plasmapheresis as first-line treatment.
timeFrame: Six months follow-up
measure: Visual and structural outcomes of acute ON in patients treated with high-dose corticosteroid-therapy versus plasmapheresis as first-line treatment.
timeFrame: 12 months follow-up
measure: 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.
timeFrame: 12 months follow-up
measure: 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.
timeFrame: Acute stage (onset)
measure: 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.
timeFrame: Acute stage (onset)
measure: 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.
timeFrame: Six months follow-up
measure: 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.
timeFrame: Six months follow-up
measure: 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.
timeFrame: 12 months follow-up
measure: 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.
timeFrame: 12 months follow-up
measure: 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.
timeFrame: Acute stage (onset)
measure: 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.
timeFrame: Acute stage (onset)
measure: 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.
timeFrame: Six months follow-up
measure: 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.
timeFrame: 12 months follow-up
measure: Diagnostic value of OCT markers (e.g. increased pRNFL) for diagnosis of MS, NMOSD, and MOGAD.
timeFrame: Acute stage (onset)
measure: Diagnostic value of OCT markers (e.g. increased pRNFL) for diagnosis of MS, NMOSD, and MOGAD.
timeFrame: Six months follow-up
measure: Prognostic value of OCT markers (e.g. increased pRNFL) for the visual outcome at 1-year follow-up.
timeFrame: 12 months follow-up
measure: Diagnostic value of OCT markers for a conversion from acute ON to clinically definite MS.
timeFrame: Acute stage (onset)
measure: Diagnostic value of OCT markers for a conversion from acute ON to clinically definite MS.
timeFrame: Six months follow-up
measure: Diagnostic value of OCT markers for a conversion from acute ON to clinically definite MS.
timeFrame: 12 months follow-up
measure: Diagnostic value of early clinical variables (i.e. visual loss and pain patterns).
timeFrame: Acute stage (onset)
measure: Diagnostic value of early clinical variables (i.e. visual loss and pain patterns).
timeFrame: Six months follow-up
measure: Diagnostic value of early clinical variables (i.e. visual loss and pain patterns).
timeFrame: 12 months follow-up
measure: Characterization of visual function in daily routine, visual QoL scores and incidence of depression at 1-year follow-up.
timeFrame: Six months follow-up
measure: Characterization of visual function in daily routine, visual QoL scores and incidence of depression at 1-year follow-up.
timeFrame: 12 months follow-up
measure: Characterization of visual function in daily routine, visual QoL scores and incidence of depression at 1-year follow-up.
timeFrame: Six months follow-up
measure: Characterization of visual function in daily routine, visual QoL scores and incidence of depression at 1-year follow-up.
timeFrame: 12 months follow-up
measure: Characterization of visual function in daily routine, visual QoL scores and incidence of depression at 1-year follow-up.
timeFrame: Six months follow-up
measure: Characterization of visual function in daily routine, visual QoL scores and incidence of depression at 1-year follow-up.
timeFrame: 12 months follow-up
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado School of Medicine
state: Colorado
city: Boston
country: United States
facility: Harvard Medical School
state: Massachusetts
city: Rochester
country: United States
facility: Departments of Neurology and Ophthalmology, Mayo Clinic
state: Minnesota
city: Buenos Aires
country: Argentina
facility: Hospital Aleman
city: Sydney
country: Australia
facility: Department of Neurology, Concord Hospital, Faculty of Medicine and Health
city: Gaborone
country: Botswana
facility: University of Botswana
city: Minas Gerais
country: Brazil
facility: Federal University of Minas Gerais, Belo Horizonte
city: Bogotá
country: Colombia
facility: Del Rosario University
city: Bogotá
country: Colombia
facility: Department of Ophthalmology, Oftlamo-Sanitas Eye Institute, School of Medicine, Fundación Universitaria Sanitas
city: Bogotá
country: Colombia
facility: Pontificia Universidad Javeriana
city: Odense
country: Denmark
facility: Department of Neurology, Slagelse, Institute for Health Research, University of Southern Denmark
city: Lyon
country: France
facility: (MIRCEM) Lyon Civil Hospices, France
city: Berlin
country: Germany
facility: Experimental and Clinical Research Center, Charité - Universitätsmedizin Berlin, Germany, Department of Neurology
city: Munich
country: Germany
facility: Institute for Clinical Neuroimmunology, LMU Clinic of Ludwig-Maximilians Universität in Munich
city: Mangalore
country: India
facility: Nitte University, Karnataka
city: Jerusalem
country: Israel
facility: Hadassah Hebrew University
city: Tel Aviv
country: Israel
facility: Sackler School of Medicine and Rabin Medical Center
city: Bologna
country: Italy
facility: University of Bologna
city: Verona
country: Italy
facility: University of Verona
city: Fukushima
country: Japan
facility: Fukushima Medical University School of Medicine
city: Seúl
country: Korea, Republic of
facility: National Cancer Center, Seúl University
city: Barcelona
country: Spain
facility: University of Barcelona
city: Barcelona
country: Spain
facility: Vall d'Hebron Barcelona Hospital Campus
city: Birmingham
country: United Kingdom
facility: University Hospitals of Birmingham
city: Oxford
country: United Kingdom
facility: Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital
city: Lusaka
country: Zambia
facility: University Teaching Hospital in Lusaka
Study officials:
affiliation: Charite University, Berlin, Germany
name: Susanna Asseyer
role: PRINCIPAL_INVESTIGATOR
affiliation: Rabin Medical Center, Tel Aviv
name: Hadas Stiebel-Kalish
role: PRINCIPAL_INVESTIGATOR
References: