An Observational, Non-interventional, Multicenter, Prospective Study to Explore the Association of MS-related Disability Worsening and Loss of Thalamus Volume.
试验速览
- 阶段
- 不适用
- 状态
- Enrolling By Invitation
- 发起方
- 入组人数
- 2,400
- 试验地点
- 2
- 主要终点
- Association between annual change in EDSS and annualized thalamic volume loss (TVL)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •Primary progressive MS (PPMS) or secondary progressive MS (SPMS) at time of enrollment
- •Not eligible to receive MRI
研究组 & 干预措施
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.
干预措施: Disease-Modifying Therapies (DMTs) (Drug)
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.
干预措施: Disease-Modifying Therapies (DMTs) (Drug)
结局指标
主要结局
Association between annual change in EDSS and annualized thalamic volume loss (TVL)
时间窗: 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).
次要结局
- Biometrica MS discrimination(months: 12 and 24)
- 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)