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

October 31, 2022 updated by: Experimental and Clinical Research Center, a cooperation between the Max Delbrück Center for Molecul

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Observational

Enrollment (Anticipated)

200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Argentina
      • Buenos Aires, Argentina
        • Not yet recruiting
        • Hospital Alemán
        • Contact:
          • Dr.
        • Contact:
          • Edgar Carnero Contentti, Dr.
        • Principal Investigator:
          • Pablo A. Lopez, Dr.
  • Australia
      • Sydney, Australia
        • Recruiting
        • Department of Neurology, Concord Hospital, Faculty of Medicine and Health
        • Contact:
          • Sundarshini Ramanathan, Dr.
        • Principal Investigator:
          • Sundarshini Ramanathan, Dr.
        • Principal Investigator:
          • Russel C Dale
  • Botswana
      • Gaborone, Botswana
        • Not yet recruiting
        • University of Botswana
        • Contact:
          • Cassandra Ocampo, Dr.
        • Principal Investigator:
          • Cassandra Ocampo, Dr.
        • Principal Investigator:
          • Jemal Shifa, Dr.
  • Brazil
      • Minas Gerais, Brazil
        • Not yet recruiting
        • Federal University of Minas Gerais, Belo Horizonte
        • Contact:
          • Marco Lana-Peixoto, Prof.
        • Principal Investigator:
          • Marco Lana-Peixoto, Prof.
  • Colombia
      • Bogotá, Colombia
        • Not yet recruiting
        • Del Rosario University
        • Contact:
          • Rodrigo Gonzales-Reyes, Dr.
        • Principal Investigator:
          • Rodrigo Gonzales-Reyes
        • Principal Investigator:
          • Ligia Alejandra De La Torre Cifuentes
      • Bogotá, Colombia
        • Not yet recruiting
        • Department of Ophthalmology, Oftlamo-Sanitas Eye Institute, School of Medicine, Fundación Universitaria Sanitas
        • Contact:
          • Alvaro Jose Mejia Vergara
      • Bogotá, Colombia
        • Not yet recruiting
        • Pontificia Universidad Javeriana
        • Contact:
          • Luis Alfonso Zarco Montero, Dr.
        • Principal Investigator:
          • Luis Alfonso Zarco Montero, Dr.
        • Sub-Investigator:
          • José Luis Peralta Uribe, Dr.
        • Sub-Investigator:
          • Carolina Garcia-Alfonso, Dr.
  • Denmark
      • Odense, Denmark
        • Recruiting
        • Department of Neurology, Slagelse, Institute for Health Research, University of Southern Denmark
        • Contact:
          • Nasrin Asgari, Prof.
        • Principal Investigator:
          • Nasrin Asgari, Prof.
  • France
      • Lyon, France
        • Not yet recruiting
        • (MIRCEM) Lyon Civil Hospices, France
        • Contact:
          • Carolin Froment Tilikete, Dr.
        • Principal Investigator:
          • Carolin Froment Tilikete, Dr.
        • Principal Investigator:
          • Romain Marignier, Prof.
  • Germany
      • Berlin, Germany
        • Recruiting
        • Experimental and Clinical Research Center, Charité - Universitätsmedizin Berlin, Germany, Department of Neurology
        • Contact:
          • Susanna Asseyer, Dr.
        • Principal Investigator:
          • Susanna Asseyer, Dr.
        • Principal Investigator:
          • Friedemann Paul, Prof.
        • Sub-Investigator:
          • Philipp Klyscz
        • Sub-Investigator:
          • Kristina Feldmann
      • Munich, Germany
        • Not yet recruiting
        • Institute for Clinical Neuroimmunology, LMU Clinic of Ludwig-Maximilians Universität in Munich
        • Contact:
          • Joachim Havla, Prof.
        • Principal Investigator:
          • Joachim Havla, Prof.
  • India
      • Mangalore, India
        • Not yet recruiting
        • Nitte University, Karnataka
        • Contact:
          • Lekha Pandit, Prof.
        • Principal Investigator:
          • Lehka Pandit, Prof.
  • Israel
      • Jerusalem, Israel
        • Not yet recruiting
        • Hadassah Hebrew University
        • Contact:
          • Netta Levin, Prof.
        • Principal Investigator:
          • Netta Levin, Prof.
        • Sub-Investigator:
          • Adi Vaknine-Dembinsky, Dr.
      • Tel Aviv, Israel
        • Recruiting
        • Sackler School of Medicine and Rabin Medical Center
        • Contact:
        • Principal Investigator:
          • Hadas Stiebel-Kalish, Prof.
        • Sub-Investigator:
          • Omer Bialer, Dr.
        • Sub-Investigator:
          • Mark Hellmann, Dr.
        • Sub-Investigator:
          • Alon Tiosano, Dr.
        • Sub-Investigator:
          • Shira Rozenblatt, Dr.
        • Sub-Investigator:
          • Adi Wilf-Yarkoni, Dr.
  • Italy
      • Bologna, Italy
        • Not yet recruiting
        • University of Bologna
        • Contact:
          • Alessandra Lugaressi, Prof.
        • Principal Investigator:
          • Alessandra Lugaressi, Prof.
        • Principal Investigator:
          • Chiara La Morgia, Dr.
      • Verona, Italy
        • Recruiting
        • University of Verona
        • Contact:
          • Sara Mariotto, Dr.
        • Principal Investigator:
          • Sara Mariotto
        • Principal Investigator:
          • Sara Carta
        • Sub-Investigator:
          • Francesca Bosello
  • Japan
      • Fukushima, Japan
        • Not yet recruiting
        • Fukushima Medical University School of Medicine
        • Contact:
          • Kazuo Fujihara, Prof.
        • Principal Investigator:
          • Kazuo Fujihara, Prof.
  • Korea, Republic of
      • Seúl, Korea, Republic of
        • Not yet recruiting
        • National Cancer Center, Seúl University
        • Contact:
          • Ho Jin Kim, Prof.
        • Principal Investigator:
          • Ho Jin Kim, Prof.
  • Spain
      • Barcelona, Spain
        • Not yet recruiting
        • University of Barcelona
        • Contact:
          • Josep Dalmau, Prof.
        • Principal Investigator:
          • Josep Dalmau, Prof.
        • Sub-Investigator:
          • Albert Saiz, Dr.
        • Sub-Investigator:
          • Bernardo Sanchez-Dalmau, Prof.
        • Sub-Investigator:
          • Sara Llufriu, Dr.
      • Barcelona, Spain
        • Not yet recruiting
        • Vall d'Hebron Barcelona Hospital Campus
        • Contact:
          • Vidal Angela, Dr.
        • Principal Investigator:
          • Vidal Angela, Dr.
        • Principal Investigator:
          • Jaume Sastre, Dr.
  • United Kingdom
      • Birmingham, United Kingdom
        • Not yet recruiting
        • University Hospitals of Birmingham
        • Contact:
          • Susan Mollan, Dr.
        • Principal Investigator:
          • Susan Mollan, Dr.
        • Sub-Investigator:
          • Fiona Chan, Dr.
      • Oxford, United Kingdom
        • Not yet recruiting
        • Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital
        • Contact:
          • Jacqueline Palace, Prof.
        • Principal Investigator:
          • Jacqueline Palace, Prof.
        • Principal Investigator:
          • Maria Isabel Leite, Dr.
  • United States
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Not yet recruiting
        • University of Colorado School of Medicine
        • Contact:
          • Jeffrey Bennett, Prof.
        • Principal Investigator:
          • Jeffrey Bennett, Prof.
        • Principal Investigator:
          • Prem S. Subramanian, Prof.
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Not yet recruiting
        • Harvard Medical School
        • Contact:
          • Michael Levy, Prof.
        • Principal Investigator:
          • Michael Levy, Prof.
        • Principal Investigator:
          • Itay Lotan, Dr.
    • Minnesota
      • Rochester, Minnesota, United States, 55902
        • Recruiting
        • Departments of Neurology and Ophthalmology, Mayo Clinic
        • Contact:
          • John Chen, Prof.
        • Principal Investigator:
          • Sean Pittock, Prof.
        • Principal Investigator:
          • Eoin P. Flanagan, Prof.
  • Zambia
      • Lusaka, Zambia
        • Not yet recruiting
        • University Teaching Hospital in Lusaka
        • Contact:
          • Deanna Saylor, Dr.
        • Principal Investigator:
          • Deanna Saylor, Dr.
        • Sub-Investigator:
          • Mashina Chomba, Dr.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Time Frame: Six months follow-up
visual acuity
Six months follow-up

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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

Investigators

  • Principal Investigator: Susanna Asseyer, Charite University, Berlin, Germany
  • Principal Investigator: Hadas Stiebel-Kalish, Rabin Medical Center, Tel Aviv

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 15, 2020

Primary Completion (Anticipated)

December 31, 2025

Study Completion (Anticipated)

December 31, 2025

Study Registration Dates

First Submitted

October 23, 2022

First Submitted That Met QC Criteria

October 31, 2022

First Posted (Actual)

November 4, 2022

Study Record Updates

Last Update Posted (Actual)

November 4, 2022

Last Update Submitted That Met QC Criteria

October 31, 2022

Last Verified

October 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACON2022

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

The datasets generated and/or analyzed during the current study are not publicly available but are available from the corresponding author upon reasonable request

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe