Effects of Dimethyl Fumarate on Cognitive Performances and Gray Matter and Thalamic Pathology in Multiple Sclerosis: a Correlation Study.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 52
- 试验地点
- 1
- 主要终点
- Change in subjects' cognitive performance
研究概览
简要总结
The goal of this observational study is to evaluate the slowing/reduction of cognitive dysfunction progression and to evaluate grey matter (GM) and thalamus structural changes in Relapsing-Remitting Multiple Sclerosis (RRMS) patients after 12 months of treatment with Dimethyl Fumarate (DMF).
The main questions it aims to answer are:
- Can DMF slow or reduce the progression of cognitive dysfunction in RRMS patients?
- Can DMF slow the reduction of brain volume in RRMS patients?
At baseline visit, RRMS patients undergo extensive neurological examination in which their disability is evaluated by using Expanded Disability Status Scale (EDSS). The efficacy assessments of this study are:
- The Brief Repeatable Neuropsychological Battery (BRB);
- Executive functions: Delis-Kaplan Function System (DKEFS) scale - Sorting Test.
All RRMS patients undergo MRI: conventional MRI measures (T2-, T1-enhancing and T1-hypointense lesions), global brain atrophy, regional brain atrophy and Diffusion Tensor Imaging (DTI) (GM and thalamus) examinations.
Six and 12 months after the baseline visit, the RRMS patients in treatment with DMF undergo the BRB, DKEFS and MRI/DTI study and neurological evaluation (EDSS).
详细描述
Dimethyl fumarate (DMF) is an oral disease-modifying therapy (DMT) approved for management of Relapsing-Remitting Multiple Sclerosis (RRMS) patients. Clinical trials have shown that DMF has a significant beneficial impact on relapse rate, disability accrual and the number of new lesions along with their volumes. In addition, a neuroprotective role of DMF has been suggested to occur on both the gray matter (GM) and thalamus. However, there are no correlation data in the literature between the effects of DMF on cognitive performance and those on the GM, with a focus on thalamic pathology in MS patients.
The primary objectives of this study are:
i) to evaluate the slowing/reduction of cognitive dysfunction progression in RRMS patients after 12 months of treatment with DMF; ii) to evaluate the effects of DMF on Magnetic Resonance Imaging (MRI) parameters in GM and thalamus.
The secondary objective is to evaluate how the effects on cognitive dysfunction progression are associated to the effect of slowing the brain volume reduction at MRI (antiatrophic effect) and to change of Diffusion Tensor Imaging (DTI) parameters that DMT might have in RRMS patients, in the GM and thalamus.
The tertiary objective is to assess whether differences exist between patients with RRMS de novo to DMF treatment and patients switching from first-line DMT to DMF.
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
- 否
入选标准
- •Patients must voluntarily give written informed consent. Patients must read and fully understand the Informed Consent Form (ICF);
- •Patient diagnosed with MS according to McDonald criteria;
- •Adult patients, males or female patients ≥ 18 years old;
- •Relapsing disease course;
- •Expanded Disability Status Scale (EDSS) ≤5.5;
- •Patients who initiate treatment with DMF 240 mg twice daily according prescribing criteria.
排除标准
- •Diagnosis of non-relapsing MS;
- •Use of experimental drug or investigational procedure during the study period;
- •Pregnancy;
- •Severe hepatic impairment;
- •Relapse or corticosteroid use within 30 days prior to baseline MRI scan;
- •Previous use of alemtuzumab, cladribine, rituximab, or mitoxantrone.
研究组 & 干预措施
RRMS patients with de novo DMF treatment
RRMS patients with de novo treatment who start DMF.
干预措施: Dimethyl Fumarate 240 MG [Tecfidera] (Drug)
RRMS patients switching to DMF.
RRMS patients who switch from first-line DMT treatment (interferon, glatiramer acetate, teriflunomide) to treatment with DMF.
干预措施: Dimethyl Fumarate 240 MG [Tecfidera] (Drug)
结局指标
主要结局
Change in subjects' cognitive performance
时间窗: Month 0 Baseline to Month 12 Follow-up
Change from baseline in DKEFS Condition 2: Sort Recognition, Sort Recognition Description Score - Card Set 1+22 at 12 months. The standard form consists of the practice card set, card set 1 and card set 2. The alternate form consists of the same practice card set, card set 3 and card set 4. Free sorting and sort recognition. In free sorting, six scores were obtained: Confirmed Correct sorts for card sets 1 and 2 (or 3 and 4 for version B), sum of confirmed Correct Sorts, Free Sorting Description score for card set 1 and 2 (or 3 and 4 for version B) and sum of Free Sorting Description scores. The total score ranged from 0 to 64. Higher values represent a better outcome.
Changes brain MRI parameters
时间窗: Month 0 Baseline to Month 12 Follow-up
Change from baseline DTI measures in the GM and thalamus at 12 months.
次要结局
- Correlation between scores of cognitive battery and brain MRI parameters(Baseline and 6 and 12 months after.)