PENTAGON: MS-Related Disability Worsening and Thalamic Volume Loss

NCT07753928 | Enrolling By Invitation

• 3 other identifiers: PENTAGONDRKS000304032025-010-f-S
• Study Type: observational
• Target: 2,400
• Locations: 1 country
• Sites: 1

Brief Summary

PENTAGON is an observational, non-interventional, multicenter, prospective cohort study conducted at approximately 20 neurology centers and affiliated radiology centers across Germany. It investigates whether loss of thalamic volume (TVL) is an independent driver of disability progression in patients with relapsing-remitting multiple sclerosis (MS). The study observes two groups: patients with active MS (receiving or about to receive first- or second-line disease-modifying therapies) and patients with progressive MS. Over a 24-month primary observation period - extendable to 72 months - MS-related disability is measured with the Expanded Disability Status Scale (EDSS), and whole-brain and thalamic volumes are quantified from standardized high-resolution T1-weighted MRI using validated deep-learning methods. The primary objective is to demonstrate that the change in MS-related disability over 24 months is inversely associated with the change in thalamic volume over the same period. No procedures beyond routine clinical care are required.

Conditions

Multiple Sclerosis, Relapsing-Remitting

Outcome Measures

Primary Outcomes (1)

• Association between annual change in EDSS and annualized thalamic volume loss (TVL)

  Pearson correlation coefficient between the annual change in EDSS (slope of linear regression of EDSS vs. time across all visits) and annualized TVL derived from consecutive high-resolution T1w MRI (Opfer et al. 2020). Significance tested at p = 0.05. Unit of measure: Pearson correlation coefficient (r), dimensionless (-1 to +1).

  months: 0 - 24

Secondary Outcomes (5)

• Disability worsening vs. TVL with normal whole brain volume loss (BVL)

  months: 0 - 24

• Short-term prediction

  months: 24 - 36

• Long-term prediction

  months: 24 - 72

• Disability change vs. BVL

  months: 0 - 24

• Biometrica MS discrimination

  months: 12 and 24

Other Outcomes (3)

• Exploratory - Deep gray-matter volume loss (DGMVL)

  months: 0 - 72

• Exploratory - Symbol Digit Modalities Test (SDMT) (optional)

  months: 0 - 72

• Exploratory - Serum neurofilament light chain (sNfL) (optional)

  months: 0 - 72

Study Arms (2)

Active MS

Adults 18-55 with relapsing-remitting MS who receive or are about to receive first- or second-line disease-modifying therapy and show disease activity (\>10 T2 lesions, or ≥1 relapse / Gd-enhancing / new or enlarging T2 lesion in the prior 12 months). Target 1,200.

Drug: Disease-Modifying Therapies (DMTs)

Progressive MS

Adults 18-55 with relapsing-remitting MS, no relapses in the last two years, with progressive disease defined clinically (disability worsening) or by imaging (abnormal whole-brain volume loss). Target 1,200.

Drug: Disease-Modifying Therapies (DMTs)

Interventions

Disease-Modifying Therapies (DMTs) DRUG

Disease-Modifying Therapies (DMTs)

Active MS; Progressive MS

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Adults with relapsing-remitting MS who are regularly seen by neurologists in an outpatient setting, sampled at approximately 40 clinical centers across Germany and other European countries.

You may qualify if:

• General
• MS diagnosed by the revised 2017 McDonald criteria
• Relapsing clinical course and history of brain MRI lesions consistent with MS
• Age 18 to 55 years, inclusive
• Active MS group - meet one disease-activity criterion:
• \>10 T2 lesions at the first visit, OR
• ≥1 documented relapse in the 12 months before the first visit, OR
• ≥1 Gd-enhancing lesion on brain MRI in the prior 12 months, OR
• ≥1 new or enlarging T2 lesion in the prior 12 months
• Receiving or about to receive first-line immune therapy (as first or second DMT), e.g., teriflunomide, ozanimod, dimethylfumarate, ponesimod, diroximelfumarate; or
• Receiving or about to receive second-line therapy after prior first-line DMT (e.g., monoclonal antibodies)
• Progressive MS group:
• No relapses in the last two years and progressive disease defined clinically (disability worsening) or by imaging (abnormal whole-brain volume loss)
• Participants initially in the active group may switch to the progressive group if they later meet its criteria.

You may not qualify if:

• Primary progressive MS (PPMS) or secondary progressive MS (SPMS) at time of enrollment
• Not eligible to receive MRI

Sponsors & Collaborators

• Jung Diagnostics GmbH: lead

Study Sites (1)

Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden

Dresden, 01307, Germany

Location

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 72 Months
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2026
• First Posted: August 10, 2026
• Study Start: July 1, 2022
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2033
• Last Updated: August 10, 2026

Record last verified: 2026-08

Locations

DE (1)