Anticipating Irreversible Disability in Neuromyelitis Optica Spectrum Disorder: a Study to Assess Disease Activity in Apparently Stable Patients

NCT07526298 | Not Yet Recruiting

• 1 other identifier: ISS 20247046 Uplitza
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The present research is an observational clinical study. The project aims to investigate astrocytic damage, assessed through biological findings such as an increase in GFAP level and/or MRI water index, in patients with NMOSD and its potential role in predicting demyelinating relapses or affecting disability outcomes. It will also explore predictors of astrocytic relapses, focusing on demographic, clinical, and immunological biomarkers like T cell responses, B cell repopulation, and cytokine levels. The goal is to identify unrecognized disease activity, providing insights for future research and clinical trials. The study will involve 8 sites in Italy: 6 NMOSD clinical centers for patient enrolment and 2 centers for bioengineering and biological analysis. Centralized analysis of the MRI images of all patients enrolled in the clinical centers will be performed by the Neuroimaging Research Unit Fase 1 of San Raffaele Hospital. A total of 50 patients will be included and they will be followed for 12 months. Comprehensive evaluation of patients, including clinical assessment, bioengineering evaluation, MRI, and blood samples, will be conducted at baseline, month 6, and month 12. To assess silent astrocytic relapses, a specialized evaluation will take place at months 3 and 9, including clinical analysis, blood samples to assess biomarkers like GFAP, a reduced MRI protocol to assess MRI water index, and bioengineering evaluation. In the case of a classical relapse, a dedicated visit will occur within 5 days of symptom onset, using the same evaluation protocol as at months 3 and 9 (MRI and biomarkers will be evaluated if not done in the month before).

Conditions

Neuromyelitis Optica Spectrum Disorders

Keywords

Relapse; Astrocytic damage; MRI; GFAP

Outcome Measures

Primary Outcomes (1)

• Identifying predictors of clinical relapse

  The primary outcomes measures are: percentage of patients with relapse, defined by the occurrence of a novel/worsening NMOSD symptom (detected by patient reported outcomes or clinical judgment or bioengineering indexes) PLUS biological findings of astrocyte damage (increase of GFAP level and/or MRI water index).

  From enrollment to 12 months

Study Arms (1)

Adult patients with NMOSD

Diagnostic Test: MRI; Diagnostic Test: Immunological Factors

Interventions

Immunological Factors DIAGNOSTIC_TEST

Immunological factors will be performed every 3 months from baseline to 1 year.

Adult patients with NMOSD

MRI DIAGNOSTIC_TEST

MRI will be performed every 3 months from baseline to 1 year.

Adult patients with NMOSD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study will include adult patients with NMOSD.

You may qualify if:

• Adult patients (age ≥18 years);
• NMOSD diagnosis with AQP4 IgG positive status assessed with a cell-based assay;
• Under rituximab treatment (standard of care) from at least 1 year and for not more than 5 years;
• Ability to provide written informed consent.

You may not qualify if:

• History of a clinical relapse or new/enlarging T2 lesion during the 6 months preceding the enrollment;
• Steroids treatment during 30 days before the enrollment;
• Any contraindication to MRI;
• Patients currently participating in a different clinical trial;
• Patients currently pregnant.

Sponsors & Collaborators

• IRCCS San Raffaele: lead
• Amgen: collaborator

Study Sites (1)

San Raffaele Hospital

Milan, Milan, 20132, Italy

Location

Related Publications (4)

• Masuda H, Mori M, Hirano S, Uzawa A, Uchida T, Muto M, Ohtani R, Aoki R, Kuwabara S. Silent progression of brain atrophy in aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder. J Neurol Neurosurg Psychiatry. 2022 Jan;93(1):32-40. doi: 10.1136/jnnp-2021-326386. Epub 2021 Aug 6.

  PMID: 34362853 BACKGROUND

• Margoni M, Gueye M, Meani A, Pagani E, Valsasina P, Storelli L, Preziosa P, Moiola L, Rocca MA, Filippi M. Substrates of 8.5-year clinical outcomes in aquaporin-4 IgG-positive neuromyelitis optica spectrum disorders. J Neurol. 2026 Feb 2;273(2):112. doi: 10.1007/s00415-026-13647-x.

  PMID: 41627519 BACKGROUND

• Lorefice L, Carotenuto A, Fenu G. Silent burden: recognising and managing invisible symptoms in neuromyelitis optica. J Neurol Neurosurg Psychiatry. 2025 Jul 16;96(8):744-752. doi: 10.1136/jnnp-2025-336041.

  PMID: 40506118 BACKGROUND

• Cacciaguerra L, Pagani E, Radaelli M, Mesaros S, Martinelli V, Ivanovic J, Drulovic J, Filippi M, Rocca MA. MR T2-relaxation time as an indirect measure of brain water content and disease activity in NMOSD. J Neurol Neurosurg Psychiatry. 2022 Apr 28:jnnp-2022-328956. doi: 10.1136/jnnp-2022-328956. Online ahead of print.

  PMID: 35483915 BACKGROUND

MeSH Terms

Conditions

Neuromyelitis Optica; Recurrence

Condition Hierarchy (Ancestors)

Myelitis, Transverse; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Optic Neuritis; Optic Nerve Diseases; Cranial Nerve Diseases; Demyelinating Diseases; Eye Diseases; Autoimmune Diseases; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Massimo Filippi, Prof.

CONTACT

+39-02-26433032; filippi.massimo@hsr.it

Mara Rocca, Prof

CONTACT

+39-02-26433054; rocca.mara@hsr.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 12 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: March 6, 2026
• First Posted: April 13, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: April 13, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)