Very High Definition Cohort: Assessment of New Prognostic Biomarkers of Disability Worsening in a Multicenter Cohort of MS Patients by Imaging, Optical Coherence Tomography and Biology
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 300
- 试验地点
- 10
- 主要终点
- Global disability progression
研究概览
简要总结
Multiple sclerosis (MS) is the most common acquired neurological disease leading to disability in young adults. MS often leads to the development of a physical and/or cognitive impairment that disables patients in their daily lives. Early use of disease modifying treatments for patients at risk of developing disability is therefore essential.
However, disability progression is very heterogeneous between patients and currently impossible to predict at the individual level. Thus, numerous studies, particularly epidemiological and imaging studies, have identified prognostic factors for the development of disability such as age, gender, number of relapses during the first years of the disease, existence of a residual disability after a first relapse, number of gadolinium-enhancing lesions on initial MRI, early brainstem and spinal cord lesions. However, these different factors only explain incompletely the progression of the physical or cognitive disability in MS patients. In particular, some components of MS pathophysiology, more related to the progressive development of disability, such as axonal degeneration or the existence of chronic inflammation of the central nervous system (CNS) are usually not measured by these biomarkers.
In this research project, the investigators will test promising biomarkers, focused on these components of the disease, on a large cohort of patients in a multicenter setting, in order to evaluate their added value to predict disability progression, in comparison with more classical biomarkers such as clinical characteristics, and brain and spinal cord lesion load.
In particular, the investigators will test:
- Imaging biomarkers extracted from brain and spinal cord MP2RAGE, brain and spinal cord QSM, brain and spinal cord relaxometry, brain diffusion and spinal cord magnetization transfer sequences
- Biomarkers extracted from optical coherence tomography (OCT)
- Biological biomarkers (serum neurofilament-light chain (NFL) and Glial Fibrillary Acidic Protein (GFAP))
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •For MS patients:
- •Inclusion Criteria:
- •The patient must be already included in the OFSEP High Definition cohort (NCT03603457).
- •The patient must have given his informed and signed consent for the inclusion in the VHD cohort.
- •The patient must be insured or beneficiary of a health insurance plan.
排除标准
- •The patient is under judicial protection.
- •The patient refuses to sign the consent.
- •It is impossible to correctly inform the patient (Inability to understand the study, language problem).
- •The patient has experienced a relapse in the previous 3 months.
- •The patient is pregnant or breast-feeding (MRI contraindicated).
- •Patient with MRI contra-indications (patient with a pacemaker, ferromagnetic vascular clip, infusion pump, neurostimulator, cochlear implants or in whom there is a suspicion of a metallic foreign body).
- •The patient has a severe psychiatric illness
- •The patient has severe chronic alcoholism
- •For healthy subjects:
- •Inclusion Criteria:
- •The healthy subject must be older than 18 years
- •The healthy subject must have given his informed and signed consent for the inclusion in the VHD cohort.
- •The healthy subject must be insured or beneficiary of a health insurance plan.
- •Exclusion Criteria:
- •The healthy subject is under judicial protection.
- •It is impossible to correctly inform the healthy subject (Inability to understand the study, language problem).
- •The healthy subject is pregnant or breast-feeding (MRI contraindicated).
- •The healthy subject has MRI contra-indications (a pacemaker, ferromagnetic vascular clip, infusion pump, neurostimulator, cochlear implants or in whom there is a suspicion of a metallic foreign body).
- •The healthy subject has a history of disease that may affect the central nervous system.
- •The healthy subject has a family history of MS.
研究组 & 干预措施
Patients with MS
250 patients with MRI, OCT and bio sample
干预措施: MRI (Other)
Healthy subjects
50 healthy subjects with MRI
干预措施: MRI (Other)
结局指标
主要结局
Global disability progression
时间窗: 2 years
Global disability progression will be scored by the Expanded disability score system (EDSS). Disability progression will be defined as an increase in the EDSS of at least 1 point if the baseline EDSS was 5.5 or less, or 0.5 point if the Baseline EDSS was
次要结局
- Between-subject, between-center and between-session coefficient of variation of measurements extracted quantitative MRI(At inclusion)
- Composite disability progression score(2 years)
- Focal inflammatory activity(2 years)
- Number of detected brain and spinal cord lesions per patient and per expert with and without the automatic tool at baseline and 2 year(At baseline and 2 year)
- Change in the Symbol Digit Modalities Test score(2 years)
- Change in the American Spinal Cord Injury Association motor sub-score(2 years)
- No evidence of disease activity 3(2 years)
- Number of brain and spinal cord lesion detected using 3D MP2RAGE sequence and the classical OFSEP sequences at baseline and 2 year(At inclusion and 2 years)
- Number of new brain and spinal cord lesion detected at 2 years using 3DMP2RAGE sequence and the classical OFSEP sequences(2 years)