An observational study in Multiple Sclerosis, sponsored by Jung Diagnostics GmbH. Enrolling by invitation at 2 sites in Germany. Open to participants aged 18 Years to 55 Years. Per ClinicalTrials.gov, last updated 2026-08-31.
Sponsored by Jung Diagnostics GmbH · Observational
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.
Rationale: Whole-brain volume loss is an established marker of tissue damage in MS, but evidence suggests thalamic and deep-gray-matter atrophy may be a distinct, possibly independent, driver of disability worsening. Once confirmed in an adequately powered longitudinal setting, pathological TVL could serve as a complementary marker of disease activity and a treatment target.
Design and data collection: Disability (EDSS) is assessed at baseline, at approximately 6-month intervals, and at 24 months; SDMT and serum neurofilament light chain (sNfL) are optional. Each participant undergoes standardized brain MRI (2021 MAGNIMS-CMSC-NAIMS protocol, including high-resolution T1w) at baseline and follow-up. Data are collected annually as part of routine care via a network of centers operating since 2015; no visit or procedure is mandated by the study. A preceding retrospective secondary-data phase validates the statistical design. Annual change in EDSS is estimated by linear regression across all visits; annualized TVL and brain volume change are estimated from consecutive T1w MRI using validated methods (Opfer et al. 2020) and the Biometrica MS / BrainLossNet pipeline.
3,264 studies on the registry are indexed under Multiple Sclerosis; 659 are open to participants now.
This study's planned enrollment of 2,400 is above the median of 100 across 970 observational studies indexed under Multiple Sclerosis.
Browse Multiple Sclerosis studies →This is the only study on the registry with Jung Diagnostics GmbH as lead sponsor.
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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.
Inclusion Criteria: General: Patients aged 15 to 55 with MS diagnosed by the revised 2017 McDonald criteria; ACTIVE MS group: a) Meet one disease-activity criterion: more than 10 T2 lesions at the first visit, OR at least one 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. b) Receiving or about to receive 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: a) no relapses in the last two years and progressive disease defined clinically (disability worsening) or by imaging (abnormal whole-brain volume loss); b) participants initially in the active group may switch to the progressive group if they later meet its criteria. Exclusion Criterion: Not eligible to receive MRI.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Line of therapy
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Adults 18-55 with a diagnosis of MS (relapsing-remitting, primary progressive, secondary progressive) 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)
Adults 18-55 with a diagnosis of MS (relapsing-remitting, primary progressive, secondary progressive) and 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)
Disease-Modifying Therapies (DMTs)
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).
Time frame: months: 0 - 24
Disability worsening vs. TVL with normal whole brain volume loss (BVL)
Association between MS-related disability worsening and thalamic volume loss in the subgroup with whole BVL in the normal range (chi-square). Unit of measure: percentage of participants with disability worsening (%).
Time frame: months: 0 - 24
Short-term prediction
Whether 24-month change in whole-brain and thalamus volume predicts disability change over the following 12 months (chi-square; regression / SVM; ROC-AUC). Unit of measure: area under the ROC curve (AUC), dimensionless.
Time frame: months: 24 - 36
Long-term prediction
Whether 24-month change in whole-brain and thalamus volume predicts disability change over the following 48 months (chi-square; regression / SVM; ROC-AUC). Unit of measure: area under the ROC curve (AUC), dimensionless.
Time frame: months: 24 - 72
Disability change vs. BVL
Pearson correlation between annual change in EDSS and annualized whole BVL. Significance tested at p = 0.05. Unit of measure: Pearson correlation coefficient (r), dimensionless (-1 to +1).
Time frame: months: 0 - 24
Biometrica MS discrimination
Sensitivity/specificity (ROC-AUC) of Biometrica MS in differentiating participants with vs. without MS-related disability worsening. Unit of measure: sensitivity and specificity (%).
Time frame: months: 12 and 24
Exploratory - Deep gray-matter volume loss (DGMVL)
DGMVL analyzed along the same objectives as the primary and secondary outcomes. Unit of measure: annualized volume change (% per year) / z-score.
Time frame: months: 0 - 72
Exploratory - Symbol Digit Modalities Test (SDMT) (optional)
Change from baseline in SDMT. Unit of measure: number of correct responses (points).
Time frame: months: 0 - 72
Exploratory - Serum neurofilament light chain (sNfL) (optional)
Change from baseline in sNfL. Unit of measure: concentration (pg/mL).
Time frame: months: 0 - 72
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
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