Multiple SclerosisPENTAGONNCT07753928
MS-Related Disability Worsening and Thalamic Volume Loss
An observational study of Multiple Sclerosis, run by Jung Diagnostics GmbH at 2 sites in Germany.
Trial summary
PENTAGON is an observational, non-interventional, multicenter, prospective cohort study conducted at approximately 20 neurology centers and affiliated radiology centers across Germany. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Disease-Modifying Therapies (DMTs)
- How many people
- 2,400 participants
- Where
- 2 sitesGermany
- Study dates
- 1 Jul 2022to 30 Jun 2033
- How long will I take part?
- 72 Months
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
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.
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 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: 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.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Germany2 sites
Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden
Dresden, 01307
Multiple Faculties
Multiple Locations
About this study
Official title: An Observational, Non-interventional, Multicenter, Prospective Study to Explore the Association of MS-related Disability Worsening and Loss of Thalamus Volume.
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.
Read the detailed description
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.
- Conditions
- Multiple Sclerosis
- Being tested
- Disease-Modifying Therapies (DMTs)
- Keywords
- active multple sclerosis, progressive multiple sclerosis
- Medical subject headings
- Multiple Sclerosis, Multiple Sclerosis, Chronic Progressive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Disease-Modifying Therapies (DMTs)Drug
Disease-Modifying Therapies (DMTs)
| Study group | Role | What they receive |
|---|---|---|
| Active MS | 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. Receives: Drug: Disease-Modifying Therapies (DMTs) | |
| Progressive MS | 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. Receives: Drug: Disease-Modifying Therapies (DMTs) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: months: 0 - 24
Secondary outcomes (5)
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 (%).
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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 (%).
Measured: months: 12 and 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2026
- Study start1 Jul 2022
- Primary completion30 Jun 2027 (estimated)
- Study completion30 Jun 2033 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 2,400 participants (estimated)
- Target duration
- 72 Months
Sponsor and investigators
- Lead sponsor
- Jung Diagnostics GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07753928
- Sponsor's protocol ID
- PENTAGON
- Other IDs
- DRKS00030403, 2025-010-f-S
- Acronym
- PENTAGON
- Status last verified
- Aug 2026
- First submitted
- 3 Aug 2026
- Last updated
- 31 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Observational, Non-interventional, Multicenter, Prospective Study to Explore the Association of MS-related Disability Worsening and Loss of Thalamus Volume.
- ClinicalTrials.gov ID
- NCT07753928
- Acronym / sponsor ID
- PENTAGON / PENTAGON
- Conditions
- Multiple Sclerosis
- Keywords
- active multple sclerosis, progressive multiple sclerosis
- Study type
- Observational
- Recruitment status
- Enrolling by invitation
- Enrolment
- 2,400 participants (estimated)
- Lead sponsor
- Jung Diagnostics GmbHIndustry (pharma, biotech, devices)
- Study start
- 1 Jul 2022 (actual)
- Primary completion
- 30 Jun 2027 (estimated)
- Study completion
- 30 Jun 2033 (estimated)
- First posted
- 10 Aug 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 72 Months
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active MS | – | Drug: Disease-Modifying Therapies (DMTs)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. |
| Progressive MS | – | 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. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Disease-Modifying Therapies (DMTs)Disease-Modifying Therapies (DMTs) | Drug | Active MS, Progressive MS |
Primary outcome
Association between annual change in EDSS and annualized thalamic volume loss (TVL)
Time frame: months: 0 - 24
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).
5 secondary outcomes
Disability worsening vs. TVL with normal whole brain volume loss (BVL)
Time frame: months: 0 - 24
Short-term prediction
Time frame: months: 24 - 36
Long-term prediction
Time frame: months: 24 - 72
Disability change vs. BVL
Time frame: months: 0 - 24
Biometrica MS discrimination
Time frame: months: 12 and 24
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Multiple Sclerosis, run by Jung Diagnostics GmbH at 2 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 31 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Association between annual change in EDSS and annualized thalamic volume loss (TVL) (time frame: months: 0 - 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2026.