Acute Optic Neuritis Network: an International Study That Invesitages Subjects With a First-ever Episode of Acute Inflammation of the Optic Nerve

Multiple Sclerosis Clinical Trial

— ACON  

Official title:

The Acute Optic Neuritis Network (ACON): a Non-interventional Prospective Multicenter Study on Diagnosis and Treatment of Acute Optic Neuritis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05605951
• Other study ID #: ACON2022
• Status: Recruiting
• Start date: August 15, 2020
• Est. completion date: December 31, 2025

Study information

• Verified date: October 2022
• Source: Experimental and Clinical Research Center, a cooperation between the Max Delbrück Center for Molecul
• Contact: Susanna Asseyer, Dr. med.
• Phone: 030450639727
• Email: susanna.asseyer[@]charite.de
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Demyelinating Diseases
• Multiple Sclerosis
• Neuritis
• Neuromyelitis Optica
• Neuromyelitis Optica Spectrum Disorder Attack
• Optic Neuritis

Intervention

Other:
• non-interventional study
observational study

Locations

Country	Name	City	State
Argentina	Hospital Aleman	Buenos Aires
Australia	Department of Neurology, Concord Hospital, Faculty of Medicine and Health	Sydney
Botswana	University of Botswana	Gaborone
Brazil	Federal University of Minas Gerais, Belo Horizonte	Minas Gerais
Colombia	Del Rosario University	Bogotá
Colombia	Department of Ophthalmology, Oftlamo-Sanitas Eye Institute, School of Medicine, Fundación Universitaria Sanitas	Bogotá
Colombia	Pontificia Universidad Javeriana	Bogotá
Denmark	Department of Neurology, Slagelse, Institute for Health Research, University of Southern Denmark	Odense
France	(MIRCEM) Lyon Civil Hospices, France	Lyon
Germany	Experimental and Clinical Research Center, Charite´ - Universita¨tsmedizin Berlin, Germany, Department of Neurology	Berlin
Germany	Institute for Clinical Neuroimmunology, LMU Clinic of Ludwig-Maximilians Universität in Munich	Munich
India	Nitte University, Karnataka	Mangalore
Israel	Hadassah Hebrew University	Jerusalem
Israel	Sackler School of Medicine and Rabin Medical Center	Tel Aviv
Italy	University of Bologna	Bologna
Italy	University of Verona	Verona
Japan	Fukushima Medical University School of Medicine	Fukushima
Korea, Republic of	National Cancer Center, Seúl University	Seúl
Spain	University of Barcelona	Barcelona
Spain	Vall d'Hebron Barcelona Hospital Campus	Barcelona
United Kingdom	University Hospitals of Birmingham	Birmingham
United Kingdom	Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital	Oxford
United States	University of Colorado School of Medicine	Aurora	Colorado
United States	Harvard Medical School	Boston	Massachusetts
United States	Departments of Neurology and Ophthalmology, Mayo Clinic	Rochester	Minnesota
Zambia	University Teaching Hospital in Lusaka	Lusaka

Sponsors (1)

Lead Sponsor	Collaborator
Experimental and Clinical Research Center, a cooperation between the Max Delbrück Center for Molecul

Countries where clinical trial is conducted

United States,  Zambia,  Argentina,  Australia,  Botswana,  Brazil,  Colombia,  Denmark,  France,  Germany,  India,  Israel,  Italy,  Japan,  Korea, Republic of,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	visual acuity	Six months follow-up
Secondary	Visual and structural outcomes of acute ON in patients treated with high-dose corticosteroid-therapy versus plasmapheresis as first-line treatment.	RNFL	Six months follow-up
Secondary	Visual and structural outcomes of acute ON in patients treated with high-dose corticosteroid-therapy versus plasmapheresis as first-line treatment.	MRI lesion score	Six months follow-up
Secondary	Visual and structural outcomes of acute ON in patients treated with high-dose corticosteroid-therapy versus plasmapheresis as first-line treatment.	MRI lesion score	12 months follow-up
Secondary	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.	RNFL	12 months follow-up
Secondary	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.	NfL (pg/ml)	Acute stage (onset)
Secondary	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.	GFAP (pg/ml)	Acute stage (onset)
Secondary	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.	NfL (pg/ml)	Six months follow-up
Secondary	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.	GFAP (pg/ml)	Six months follow-up
Secondary	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.	NfL (pg/ml)	12 months follow-up
Secondary	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.	GFAP (pg/ml)	12 months follow-up
Secondary	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.	MOG-IgG ratio	Acute stage (onset)
Secondary	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.	AQP4-IgG ratio	Acute stage (onset)
Secondary	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.	MOG-IgG IgG ratio	Six months follow-up
Secondary	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.	AQP4-IgG ratio	12 months follow-up
Secondary	Diagnostic value of OCT markers (e.g. increased pRNFL) for diagnosis of MS, NMOSD, and MOGAD.	pRNFL	Acute stage (onset)
Secondary	Diagnostic value of OCT markers (e.g. increased pRNFL) for diagnosis of MS, NMOSD, and MOGAD.	pRNFL	Six months follow-up
Secondary	Prognostic value of OCT markers (e.g. increased pRNFL) for the visual outcome at 1-year follow-up.	pRNFL	12 months follow-up
Secondary	Diagnostic value of OCT markers for a conversion from acute ON to clinically definite MS.	OCT markers	Acute stage (onset)
Secondary	Diagnostic value of OCT markers for a conversion from acute ON to clinically definite MS.	OCT markers	Six months follow-up
Secondary	Diagnostic value of OCT markers for a conversion from acute ON to clinically definite MS.	OCT markers	12 months follow-up
Secondary	Diagnostic value of early clinical variables (i.e. visual loss and pain patterns).	pain intensity	Acute stage (onset)
Secondary	Diagnostic value of early clinical variables (i.e. visual loss and pain patterns).	pain intensity	Six months follow-up
Secondary	Diagnostic value of early clinical variables (i.e. visual loss and pain patterns).	pain intensity	12 months follow-up
Secondary	Characterization of visual function in daily routine, visual QoL scores and incidence of depression at 1-year follow-up.	NEI-VFQ-Score	Six months follow-up
Secondary	Characterization of visual function in daily routine, visual QoL scores and incidence of depression at 1-year follow-up.	NEI-VFQ-Score	12 months follow-up
Secondary	Characterization of visual function in daily routine, visual QoL scores and incidence of depression at 1-year follow-up.	BDI-II Score	Six months follow-up
Secondary	Characterization of visual function in daily routine, visual QoL scores and incidence of depression at 1-year follow-up.	BDI-II Score	12 months follow-up
Secondary	Characterization of visual function in daily routine, visual QoL scores and incidence of depression at 1-year follow-up.	EuroQol 5-Dimension EQ-5D-index	Six months follow-up
Secondary	Characterization of visual function in daily routine, visual QoL scores and incidence of depression at 1-year follow-up.	EuroQol 5-Dimension EQ-5D-index	12 months follow-up