Sociocognitive Intervention and Rehabilitation Program in Multiple Sclerosis: Implications for Cognitive Reserve and Metacognition
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 130
- 试验地点
- 2
- 主要终点
- Montreal Cognitive Assessment - MoCA (neuropsychological test)
研究概览
简要总结
Multiple Sclerosis (MS) is a chronic autoimmune disease of the central nervous system, involving inflammation, demyelination, and neurodegeneration. It is the most common non-traumatic disabling disease affecting young adults. MS is characterized by its heterogeneity and unpredictable course, which make both evaluation and treatment complex. Patients may present with motor, sensory, cognitive, and neuropsychiatric symptoms, all of which have a significant impact on quality of life.
With regard to cognition, the impact of cognitive impairment in MS remains underestimated. However, it is observed in approximately 40-65% of patients and may be present at all stages of the disease, including the earliest ones (patients with low levels of disability and Clinically Isolated Syndromes - CIS).
Notably, cognitive alterations appear to precede structural abnormalities on magnetic resonance imaging (MRI), representing a potential marker of disease activity.
Therefore, early diagnosis and characterization of MS-related cognitive impairment are essential, followed by the implementation of patient-tailored cognitive rehabilitation programs, which have recently been shown to exert long-term effects persisting beyond the treatment period.
The project aims to conduct a single-center, randomized, pragmatic, prospective clinical trial with blinded outcome assessment. Its primary objective is to evaluate the efficacy of an innovative sociocognitive rehabilitation program in patients diagnosed with multiple sclerosis.
In addition, the study seeks to characterize cognitive phenotypes in MS, investigate the role of cognitive reserve and metacognition in the effectiveness of the intervention, and correlate neuropsychological findings with other disease biomarkers, with the ultimate goal of proposing a predictive model of disease progression.
详细描述
The REACT-MS project is designed as a Phase IIa, single-center, randomized, pragmatic, and prospective clinical trial with blinded outcome assessment, following the PROBE methodology. Its overarching aim is to evaluate the efficacy of an innovative sociocognitive rehabilitation program in patients with multiple sclerosis (MS). Beyond this primary goal, the study also intends to characterize cognitive phenotypes in MS, investigate the role of cognitive reserve and metacognition in modulating the effectiveness of the intervention, and correlate neuropsychological performance with clinical, neuroimaging, and biochemical biomarkers in order to propose a predictive model of cognitive disease progression.
The research team is composed of neurologists and neuropsychologists from the ULS Coimbra and University of Coimbra, with extensive expertise in MS care, clinical neuropsychology, biomarker research, and clinical trial coordination. The principal investigator and co-investigators bring a strong record of clinical studies, competitive funding and international publications.
Multiple sclerosis is a chronic, autoimmune, demyelinating disease of the central nervous system characterized by inflammation, neurodegeneration, and an unpredictable clinical course. It is the leading non-traumatic cause of disability in young adults. In addition to motor and sensory symptoms, cognitive impairment affects between 40 and 65 percent of patients and can appear even in the earliest stages of the disease. Often underestimated, these deficits may precede structural abnormalities detectable by magnetic resonance imaging, functioning as early markers of disease activity. Timely diagnosis and the implementation of patient-tailored cognitive rehabilitation programs have shown sustained benefits that extend beyond the intervention period, which underscores the rationale for this study.
The study will randomize participants into an intervention arm and a control arm. Only those in the intervention group will undergo a combined program consisting of weekly sociocognitive rehabilitation sessions using the COGWEB platform and an emotional processing intervention called EMOPRINT. Most sessions will be home-based and delivered online, with only one in-person session scheduled every three months to minimize dropout and fatigue. This intervention will last for one year. A comprehensive baseline assessment will be conducted, including clinical and demographic data, disability scoring with the EDSS, magnetic resonance imaging parameters such as lesion load and brain atrophy, and serum biomarkers including neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP). Neuropsychological testing will encompass measures of global cognition, processing speed, memory, language, attention, executive functions, and social cognition. Questionnaires addressing fatigue, mood, quality of life, and cognitive reserve will also be included, and several instruments will be adapted to assess metacognition. Participants will be reassessed at 12 and 24 months to enable longitudinal monitoring of cognitive and clinical outcomes.
Data will be collected through both direct clinical assessment and electronic health records. Each participant will be assigned a unique identifier to ensure confidentiality, and data will be managed using an electronic case report form (eCRF) implemented on the REDCap platform. Secure data storage, anonymization procedures, and standardized operational protocols will be applied in strict compliance with the General Data Protection Regulation (GDPR), national legislation, and the principles of the Declaration of Helsinki. Data will be archived for five years, while scientific results may be shared in peer-reviewed publications and open-access databases with full protection of participant privacy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
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
- •Patients diagnosed with Multiple Sclerosis;
- •Complete clinical assessment (neuroimaging biomarkers-MRI, neuropsychological and biochemical biomarkers-cerebrospinal fluid and serum)
- •Age between 18-55 years;
- •Portuguese native language;
- •Fulfil the criteria for cognitive impairment as defined by either the BICAMS- with one or more test scores below the 5th percentile relative to the control group - and/or the BRBN-T - with at least two test scores below the 5th percentile relative to the control group;
- •Present deficits in social cognition.
排除标准
- •MoCA score <23;
- •History of traumatic brain injury resulting in loss of consciousness;
- •Severe language, visual, or auditory impairments;
- •Current or past use of antipsychotic medication;
- •Alcohol, drug, or other substance abuse;
- •Medical conditions that contraindicate MRI.
结局指标
主要结局
Montreal Cognitive Assessment - MoCA (neuropsychological test)
时间窗: At baseline, follow-up 12 months, 18 months and follow-up 24 months
Cognitive screening; Score 0-30 (0- worst outcome; 30- best outcome)
Ekman's Faces Test - EFT (neuropsychological test)
时间窗: At baseline, follow-up 12 months, 18 months and follow-up 24 months
Social cognition and metacognition; Score 0-35 (0- worst outcome; 35- best outcome)
Reading the Mind in the Eyes Test - RMET (neuropsychological test)
时间窗: At baseline, follow-up 12 months, 18 months and follow-up 24 months
Social cognition and metacognition; Score 0-36 (0- worst outcome; 36- best outcome)
Symbol Digit Modalities Test - SDMT (part of BICAMS-Brief International cognitive Assessment Multiple Sclerosis neuropsychological test)
时间窗: At baseline, follow-up 12 months, 18 months and follow-up 24 months
Processing speed measures and metacognition; Score 0-110 adjusted for age and education (score enables an intermediate T-score allowing for classification- Presence of Impairment \< 34.5).
California Verbal Learning Test - CVLT-II (part of BICAMS-Brief International cognitive Assessment Multiple Sclerosis neuropsychological test)
时间窗: At baseline, follow-up 12 months, 18 months and follow-up 24 months
Verbal learning, memory and metacognition; Score 0-80 adjusted for age (score enables an intermediate T-score allowing for classification- Presence of Impairment \< 34.5).
Brief Visuospatial Memory Test - BVMT-R (part of BICAMS-Brief International cognitive Assessment Multiple Sclerosis neuropsychological test)
时间窗: At baseline, follow-up 12 months, 18 months and follow-up 24 months
Visual learning, memory and metacognition; Score 0-36 adjusted for age (score enables an intermediate T-score allowing for classification- Presence of Impairment \< 34.5).
Paced Auditory Serial Addition Test - PASAT (part of BRBN-T: Brief repeatable battery of neuropsychological tests)
时间窗: At baseline, follow-up 12 months, 18 months and follow-up 24 months
Processing speed measures and metacognition; Score Score 0-60 adjusted for age, gender and education (score enables an intermediate T-score allowing for classification- Presence of Impairment \< 34.5)
Selective Reminding Test - SRT (part of BRBN-T: Brief repeatable battery of neuropsychological tests)
时间窗: At baseline, follow-up 12 months, 18 months and follow-up 24 months
Verbal learning, memory and metacognition; Score 0-70 adjusted for age, gender (0-male; 1-female) and education (score enables an intermediate T-score allowing for classification- Presence of Impairment \< 34.5).
10/36 Spatial Recall Test - SPART (part of BRBN-T: Brief repeatable battery of neuropsychological tests)
时间窗: At baseline, follow-up 12 months, 18 months and follow-up 24 months
Visual learning, memory and metacognition; Score 0-30 adjusted for age, gender and education (score enables an intermediate T-score allowing for classification- Presence of Impairment \< 34.5).
Word List Generation Test - WLG (part of BRBN-T: Brief repeatable battery of neuropsychological tests)
时间窗: At baseline, follow-up 12 months, 18 months and follow-up 24 months
Language measures and metacognition; Score 0-67 adjusted for gender and education (score enables an intermediate T-score allowing for classification- Presence of Impairment \< 34.5).
Boston Naming Test - BNT (neuropsychological test)
时间窗: At baseline, follow-up 12 months, 18 months and follow-up 24 months
Language measures: Score 0-30, calculated based on the number of items correctly named spontaneously.
d2 Test of Attention (neuropsychological test)
时间窗: At baseline, follow-up 12 months, 18 months and follow-up 24 months
Measures processing speed, rule compliance, and quality of performance, allowing for an estimation of individual attention, according to several metrics. There is no specified cut-off.
Irregular Word Reading Test - TeLPI (neuropsychological test)
时间窗: At baseline.
Premorbid intelligence, ability to read irregularly spelled words ; there is no specified cut-off.
Stroop Test (neuropsychological test)
时间窗: At baseline, follow-up 12 months, 18 months and follow-up 24 months
Measures cognitive flexibility, processing speed, and executive function; Score varies according to speed and accuracy abilities. There is no specified cut-off.
次要结局
- Modified Fatigue Impact Scale - MFIS (PROM: Patient Reported Outcome Measure)(At baseline, follow-up 12 months, 18 months and follow-up 24 months)
- Cognitive Reserve Index Questionnaire - CRIq(At baseline)
- Hospital Anxiety and Depression Scale - HADS (PROM: Patient Reported Outcome Measure)(At baseline, follow-up 12 months, 18 months and follow-up 24 months)
- World Health Organization Quality of Life short-form - WHOQOL-Bref (PROM: Patient Reported Outcome Measure)(At baseline, follow-up 12 months, 18 months and follow-up 24 months)
- Neurofilament Light chain (NfL): pg/mL(At baseline, follow-up 12 months, 18 months and follow-up 24 months)
- Glial Fibrillary Acidic Protein (GFAP): pg/mL(At baseline, follow-up 12 months, 18 months and follow-up 24 months)
- Number of T2 lesions in brain MRI(At baseline, follow-up 12 months and follow-up 24 months)
- Status of MRI T2 lesions(At baseline, 12 months and 24 months.)
- MRI lesion load (mm3)(At baseline, 12 months, 18 months and 24 months.)
- MRI- affected brain region (cerebellum)(At baseline, 12 months and 24 months.)
- MRI- affected brain region (spinal cord)(At baseline, 12 months and 24 months.)
- MRI- affected brain region (cortical/juxtacortical)(At baseline, 12 months and 24 months.)
- MRI- affected brain region (brainstem)(At baseline, 12 months and 24 months.)
研究者
Sonia Batista
Principal Investigator, MD, PhD
Unidade Local de Saúde de Coimbra, EPE