Predictors of Progression Independent of Relapse Activity in Relapsing Remitting Multiple Sclerosis

NCT07762040 | Not Yet Recruiting DMC

• 1 other identifier: 04-2026-100514
• Study Type: observational
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this prospective observational cohort study is to determine the frequency of progression independent of relapse activity (PIRA) and identify its clinical, radiological, neuroaxonal, and functional predictors in patients with early relapsing-remitting multiple sclerosis (RRMS). The study aims to facilitate early identification of patients at increased risk of disability progression independent of relapses and to support individualized therapeutic decision-making. The main questions it aims to answer are: What is the frequency of PIRA in patients with early RRMS? Which demographic and clinical characteristics are associated with the development of PIRA? Which MRI biomarkers, including lesion burden, brain atrophy, spinal cord involvement, and paramagnetic rim lesions (where available), are associated with PIRA? Can optical coherence tomography (OCT) measurements, including peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell-inner plexiform layer (mGCIPL) thickness, predict PIRA? Are serum biomarkers, including neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP), associated with an increased risk of PIRA? Which baseline factors independently predict disability progression? Participants will undergo comprehensive baseline and follow-up assessments, including collection of demographic and clinical data, neurological examination with Expanded Disability Status Scale (EDSS) scoring, brain and spinal cord MRI, OCT assessment, laboratory evaluation of serum biomarkers (where available), and validated functional and patient-reported outcome measures. Participants will be followed longitudinally to identify confirmed disability accumulation (CDA) and classify disability progression as PIRA or relapse-associated worsening (RAW). The primary outcome is the occurrence of PIRA, defined as confirmed disability accumulation independent of clinical relapses during follow-up. Secondary outcomes include identification of independent clinical, imaging, OCT, and laboratory predictors of PIRA and evaluation of their association with long-term disability progression. The findings may improve early risk stratification and support timely initiation of high-efficacy disease-modifying therapies in patients with early RRMS.

Conditions

Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• Proportion of participants who develop progression independent of relapse activity (PIRA) during the 2-year follow-up

  Percentage of participants who meet the predefined study criteria for confirmed progression independent of relapse activity (PIRA), based on Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC) criteria in the absence of clinical relapse.

  Baseline assessment with follow-up evaluations every 6 months for 24 months

Secondary Outcomes (3)

• Adjusted odds ratio for development of PIRA according to baseline MRI biomarkers

  Baseline assessment with follow-up evaluations every 12 months for 24 months

• Adjusted odds ratio for development of PIRA according to baseline optical coherence tomography (OCT) biomarkers

  Baseline assessment with follow-up evaluations every 12 months for 24 months

• Adjusted odds ratio for development of PIRA according to baseline visual evoked potential (VEP) P100 latency.

  Baseline assessment with follow-up evaluations every 6 months for 24 months

Study Arms (1)

relapsing remitting multiple sclerosis

Patients with early relapsing-remitting multiple sclerosis enrolled in the study and followed prospectively to determine the occurrence of progression independent of relapse activity (PIRA). Participants will subsequently be classified into PIRA and non-PIRA groups according to the study outcome.

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Patients with early relapsing-remitting multiple sclerosis (RRMS) will be recruited consecutively from the Neurology Department, Assiut University Hospital, and followed prospectively for 24 months.

You may qualify if:

• RRMS diagnosis per 2024 McDonald Criteria Disease duration ≤ 5 years from disease onset At least 1 year on disease-modifying therapy (DMT) Age 18-55 years (both sexes) Written informed consent obtained

You may not qualify if:

• Alternative diagnosis confirmed (e.g., NMOSD, vasculitis)
• Confirmed RAW
• SPMS or progressive onset at baseline
• Any systemic or neurological disorders affecting either mobility or cognition
• Psychoactive drug use
• Recent optic neuritis within the previous six months.
• Any ophthalmological condition known to affect retinal nerve fiber layer (RNFL) or ganglion cell-inner plexiform layer (GCIPL) thickness.
• Glaucoma. Diabetic retinopathy. Retinal vascular disease. High myopia (\>6 diopters). Previous ocular trauma or intraocular surgery (except uncomplicated cataract surgery \>6 months).
• Media opacity preventing reliable OCT acquisition.
• Incomplete follow up or poor compliance

Sponsors & Collaborators

• Assiut University: lead

Study Sites (1)

Assiut university neurology hospital

Asyut, Asyut Governorate, 71515, Egypt

Location

MeSH Terms

Conditions

Multiple Sclerosis

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• omnia A badry, assistant

  Assiut University neurology Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

omnia A badry, assistant

CONTACT

+201017772726; omniaelbadry952@gmail.com

anwar M Ali, Professor

CONTACT

+201030361010; Anwarmoha2006@aun.edu.eg

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 2 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Lecturer

Study Record Dates

• First Submitted: July 29, 2026
• First Posted: August 13, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: August 13, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)