Multiple SclerosisREACT-MSNCT07734675
Sociocognitive Intervention and Rehabilitation Program in Multiple Sclerosis
A study testing Sociocognitive rehabilitation via COGWEB platform combined with an emotional processing intervention. in people with Multiple Sclerosis, run by Sonia Batista at 2 sites in Portugal.
Trial summary
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. 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?
- Sociocognitive rehabilitation via COGWEB platform combined with an emotional processing intervention.
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 130 participants
- Where
- 2 sitesPortugal
- Study dates
- 1 Sep 2026to 31 Dec 2027
- Phase
- Interventional
- 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
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Clinical Trials Unit do Centro Académico Clínico de Coimbra CTU CTU-CACC contact
Clinical Trials Unit - Coimbra Academic Clinical Center CTU CTU-CACC contact
Portugal2 sites
Local Health Unit of Coimbra
Coimbra, Coimbra District, 3004-561
Unidade Local de Saude de Coimbra
Coimbra, Coimbra District
Clinical Trials Unit - Coimbra Academic Clinical Center CTU-CACC, +351239400400 ext. 8408, ctu-cacc@ulscoimbra.min-saude.pt
Sonia Batista, MD, PhD
About this study
Official title: Sociocognitive Intervention and Rehabilitation Program in Multiple Sclerosis: Implications for Cognitive Reserve and Metacognition
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).
Read more
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.
Read the detailed description
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.
The study aims to recruit 130 patients, with 65 participants per arm. Statistical analyses will include both descriptive and inferential methods using SPSS and R. The trial has been planned over a period of 36 months, comprising two months of preparation, one month for ethical approvals, three months for project implementation, twelve months for recruitment, six months for data analysis, and six months for reporting and publication. Ethical oversight will be provided by the Research Ethics Committee of ULS Coimbra, and the study will adhere to ICH-GCP standards and the Declaration of Helsinki.
The project incorporates contingency planning to address recruitment challenges, including referral collaborations with other hospitals in the central region of Portugal. Adherence is not expected to be a major limitation given the home-based structure of the intervention, which minimizes burden and facilitates patient compliance.
The main innovation of REACT-MS lies in the implementation of a combined sociocognitive and emotional rehabilitation program, delivered largely online and adapted to the needs of MS patients. This dual approach aims to enhance cognitive performance and facial emotion recognition while reducing fatigue-related barriers to participation. Moreover, the study integrates clinical, neuroimaging, and biochemical biomarkers into a predictive framework that could inform individualized prognostic modeling of cognitive outcomes.
The expected impact is significant at both clinical and scientific levels. By shifting from a dichotomous classification of preserved versus impaired cognition to the definition of cognitive phenotypes, the project may contribute to more personalized rehabilitation strategies. The integration of cognitive reserve and metacognition is anticipated to explain individual variability in rehabilitation outcomes, as these concepts have been associated with improved coping mechanisms and resilience of brain networks in the context of MS. Ultimately, the project has the potential to establish new predictive markers of disease progression, to inform clinical practice, and to set the stage for future multicenter trials, while offering MS patients sustainable and effective rehabilitation approaches that improve long-term quality of life.
- Conditions
- Multiple Sclerosis
- Being tested
- Sociocognitive rehabilitation via COGWEB platform combined with an emotional processing intervention.
- Keywords
- Metacognition, Sociocognitive Intervention, Rehabilitation, Clinically Isolated Syndromes, Relapsing-remitting multiple sclerosis, Cognitive Impairment, Autoimmune Disease
- Medical subject headings
- Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting, Cognitive Dysfunction, Autoimmune Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sociocognitive rehabilitation via COGWEB platform combined with an emotional processing intervention.Behavioural
Participants in the study group will subjected weekly sessions of sociocognitive rehabilitation using the COGWEB platform, combined with an emotional processing intervention, aimed at enhancing cognitive abilities and facial expression recognition.
Most sessions will be conducted online in a home-based setting, with only one in-person session required every three months in a hospital environment.
The dual intervention will be administered over a 12-month period.
| Study group | Role | What they receive |
|---|---|---|
| Rehabilitation Group | Experimental | Not described Receives: Behavioral: Sociocognitive rehabilitation via COGWEB platform combined with an emotional processing intervention. |
| Control Group | No intervention | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Montreal Cognitive Assessment - MoCA (neuropsychological test)
Cognitive screening; Score 0-30 (0- worst outcome; 30- best outcome)
Measured: At baseline, follow-up 12 months, 18 months and follow-up 24 months
Ekman's Faces Test - EFT (neuropsychological test)
Social cognition and metacognition; Score 0-35 (0- worst outcome; 35- best outcome)
Measured: At baseline, follow-up 12 months, 18 months and follow-up 24 months
Reading the Mind in the Eyes Test - RMET (neuropsychological test)
Social cognition and metacognition; Score 0-36 (0- worst outcome; 36- best outcome)
Measured: At baseline, follow-up 12 months, 18 months and follow-up 24 months
Symbol Digit Modalities Test - SDMT (part of BICAMS-Brief International cognitive Assessment Multiple Sclerosis neuropsychological test)
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).
Measured: At baseline, follow-up 12 months, 18 months and follow-up 24 months
California Verbal Learning Test - CVLT-II (part of BICAMS-Brief International cognitive Assessment Multiple Sclerosis neuropsychological test)
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).
Measured: At baseline, follow-up 12 months, 18 months and follow-up 24 months
Brief Visuospatial Memory Test - BVMT-R (part of BICAMS-Brief International cognitive Assessment Multiple Sclerosis neuropsychological test)
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).
Measured: At baseline, follow-up 12 months, 18 months and follow-up 24 months
Paced Auditory Serial Addition Test - PASAT (part of BRBN-T: Brief repeatable battery of neuropsychological tests)
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)
Measured: At baseline, follow-up 12 months, 18 months and follow-up 24 months
Selective Reminding Test - SRT (part of BRBN-T: Brief repeatable battery of neuropsychological tests)
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).
Measured: At baseline, follow-up 12 months, 18 months and follow-up 24 months
10/36 Spatial Recall Test - SPART (part of BRBN-T: Brief repeatable battery of neuropsychological tests)
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).
Measured: At baseline, follow-up 12 months, 18 months and follow-up 24 months
Word List Generation Test - WLG (part of BRBN-T: Brief repeatable battery of neuropsychological tests)
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).
Measured: At baseline, follow-up 12 months, 18 months and follow-up 24 months
Boston Naming Test - BNT (neuropsychological test)
Language measures: Score 0-30, calculated based on the number of items correctly named spontaneously.
Measured: At baseline, follow-up 12 months, 18 months and follow-up 24 months
d2 Test of Attention (neuropsychological test)
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.
Measured: At baseline, follow-up 12 months, 18 months and follow-up 24 months
Irregular Word Reading Test - TeLPI (neuropsychological test)
Premorbid intelligence, ability to read irregularly spelled words ; there is no specified cut-off.
Measured: At baseline.
Stroop Test (neuropsychological test)
Measures cognitive flexibility, processing speed, and executive function; Score varies according to speed and accuracy abilities. There is no specified cut-off.
Measured: At baseline, follow-up 12 months, 18 months and follow-up 24 months
Secondary outcomes (13)
Modified Fatigue Impact Scale - MFIS (PROM: Patient Reported Outcome Measure)
Fatigue; Score 0-84 (Significant fatigue >= 38)
Measured: At baseline, follow-up 12 months, 18 months and follow-up 24 months
Cognitive Reserve Index Questionnaire - CRIq
Cognitive reserve: Score 0-24, the higher the score, the higher the cognitive reserve. There is no specified cut-off.
Measured: At baseline
Hospital Anxiety and Depression Scale - HADS (PROM: Patient Reported Outcome Measure)
Anxiety and depression; Score 0-21, normal (0-7); low risk (8-10); moderate risk (11-14); high risk (15-21).
Measured: 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)
Quality of life; evaluates four main domains: physical health, psychological health, social relationships and family/finantial environment ; Scoring requires averaging the items within each domain to calculate raw scores, which are then linearly transformed to a 0-100 scale. Higher scores denote a higher perceived quality of life.
Measured: At baseline, follow-up 12 months, 18 months and follow-up 24 months
Neurofilament Light chain (NfL): pg/mL
Quantification of biochemical central markers in serum; Healthy individuals frequently present < 10 pg/mL (according to age); expected levels for patients in relapse: > 10 pg/mL.
Measured: At baseline, follow-up 12 months, 18 months and follow-up 24 months
Glial Fibrillary Acidic Protein (GFAP): pg/mL
Quantification of biochemical central markers in serum. Levels are influenced by age, sex, and BMI. Currently lacking literature cut-off values for MS patients.
Measured: At baseline, follow-up 12 months, 18 months and follow-up 24 months
Number of T2 lesions in brain MRI
Number of new brain lesions (nº).
Measured: At baseline, follow-up 12 months and follow-up 24 months
Status of MRI T2 lesions
Presence of Gd-enhancing lesions: Active/not active.
Measured: At baseline, 12 months and 24 months.
MRI lesion load (mm3)
Measures the total volume of hyperintense (bright) spots on T2 or FLAIR MRI sequences.
Measured: At baseline, 12 months, 18 months and 24 months.
MRI- affected brain region (cerebellum)
Existence of brain lesions in cerebellum: yes/no.
Measured: At baseline, 12 months and 24 months.
MRI- affected brain region (spinal cord)
Existence of brain lesions in the spinal cord: yes/no.
Measured: At baseline, 12 months and 24 months.
MRI- affected brain region (cortical/juxtacortical)
Existence of brain lesions in the cortical/juxtacortical regions: yes/no.
Measured: At baseline, 12 months and 24 months.
MRI- affected brain region (brainstem)
Existence of brain lesions in the brainstem: yes/no.
Measured: At baseline, 12 months and 24 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2026
- Study start1 Sep 2026 (estimated)
- Primary completion30 Jun 2027 (estimated)
- Study completion31 Dec 2027 (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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Phase IIa randomized clinical trial, pragmatic, prospective, and single-center, with blinded outcome assessment (PROBE methodology: Prospective, Randomized, Open-label, Blinded Endpoint).
- Masking
- None (open label)
- Enrolment
- 130 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sonia Batista
- Sponsor type
- University, hospital or other
- Collaborators
- Unidade Local de Saúde de Coimbra, EPE
- Responsible party
- Sponsor-investigator, Sonia Batista, Unidade Local de Saúde de Coimbra, EPE
- Investigators
- Sonia Batista, MD, PhD, Principal investigator, Unidade Local de Saude de CoimbraIrina Santos, MPSI, Principal investigator, University of Coimbra
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07734675
- Sponsor's protocol ID
- 2025-OT-1
- Other IDs
- 312/25 CE
- Acronym
- REACT-MS
- Status last verified
- Jul 2026
- First submitted
- 14 Jul 2026
- Last updated
- 29 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sociocognitive Intervention and Rehabilitation Program in Multiple Sclerosis: Implications for Cognitive Reserve and Metacognition
- ClinicalTrials.gov ID
- NCT07734675
- Acronym / sponsor ID
- REACT-MS / 2025-OT-1
- Conditions
- Multiple Sclerosis
- Keywords
- Metacognition, Sociocognitive Intervention, Rehabilitation, Clinically Isolated Syndromes, Relapsing-remitting multiple sclerosis, Cognitive Impairment, Autoimmune Disease
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 130 participants (estimated)
- Lead sponsor
- Sonia BatistaUniversity, hospital or other
- Collaborators
- Unidade Local de Saúde de Coimbra, EPE
- Study start
- 1 Sep 2026 (estimated)
- Primary completion
- 30 Jun 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 29 Jul 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.
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.
Detailed description
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.
The study aims to recruit 130 patients, with 65 participants per arm. Statistical analyses will include both descriptive and inferential methods using SPSS and R. The trial has been planned over a period of 36 months, comprising two months of preparation, one month for ethical approvals, three months for project implementation, twelve months for recruitment, six months for data analysis, and six months for reporting and publication. Ethical oversight will be provided by the Research Ethics Committee of ULS Coimbra, and the study will adhere to ICH-GCP standards and the Declaration of Helsinki.
The project incorporates contingency planning to address recruitment challenges, including referral collaborations with other hospitals in the central region of Portugal. Adherence is not expected to be a major limitation given the home-based structure of the intervention, which minimizes burden and facilitates patient compliance.
The main innovation of REACT-MS lies in the implementation of a combined sociocognitive and emotional rehabilitation program, delivered largely online and adapted to the needs of MS patients. This dual approach aims to enhance cognitive performance and facial emotion recognition while reducing fatigue-related barriers to participation. Moreover, the study integrates clinical, neuroimaging, and biochemical biomarkers into a predictive framework that could inform individualized prognostic modeling of cognitive outcomes.
The expected impact is significant at both clinical and scientific levels. By shifting from a dichotomous classification of preserved versus impaired cognition to the definition of cognitive phenotypes, the project may contribute to more personalized rehabilitation strategies. The integration of cognitive reserve and metacognition is anticipated to explain individual variability in rehabilitation outcomes, as these concepts have been associated with improved coping mechanisms and resilience of brain networks in the context of MS. Ultimately, the project has the potential to establish new predictive markers of disease progression, to inform clinical practice, and to set the stage for future multicenter trials, while offering MS patients sustainable and effective rehabilitation approaches that improve long-term quality of life.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Phase IIa randomized clinical trial, pragmatic, prospective, and single-center, with blinded outcome assessment (PROBE methodology: Prospective, Randomized, Open-label, Blinded Endpoint).
| Arm | Type | Receives |
|---|---|---|
| Rehabilitation Group | Experimental | Behavioral: Sociocognitive rehabilitation via COGWEB platform combined with an emotional processing intervention. |
| Control Group | No intervention | – |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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;
Key exclusion criteria (6 listed)
- 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;
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 |
|---|---|---|
| Sociocognitive rehabilitation via COGWEB platform combined with an emotional processing intervention.Participants in the study group will subjected weekly sessions of sociocognitive rehabilitation using the COGWEB platform, combined with an emotional processing intervention, aimed at enhancing cognitive abilities and facial expression recognition. Most sessions will be conducted online in a home-based setting, with only one in-person session required every three months in a hospital environment. The dual intervention will be administered over a 12-month period. | Behavioural | Rehabilitation Group |
Primary outcome
Montreal Cognitive Assessment - MoCA (neuropsychological test)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: At baseline.
Premorbid intelligence, ability to read irregularly spelled words ; there is no specified cut-off.
Stroop Test (neuropsychological test)
Time frame: 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.
13 secondary outcomes
Modified Fatigue Impact Scale - MFIS (PROM: Patient Reported Outcome Measure)
Time frame: At baseline, follow-up 12 months, 18 months and follow-up 24 months
Cognitive Reserve Index Questionnaire - CRIq
Time frame: At baseline
Hospital Anxiety and Depression Scale - HADS (PROM: Patient Reported Outcome Measure)
Time frame: 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)
Time frame: At baseline, follow-up 12 months, 18 months and follow-up 24 months
Neurofilament Light chain (NfL): pg/mL
Time frame: At baseline, follow-up 12 months, 18 months and follow-up 24 months
Glial Fibrillary Acidic Protein (GFAP): pg/mL
Time frame: At baseline, follow-up 12 months, 18 months and follow-up 24 months
Number of T2 lesions in brain MRI
Time frame: At baseline, follow-up 12 months and follow-up 24 months
Status of MRI T2 lesions
Time frame: At baseline, 12 months and 24 months.
MRI lesion load (mm3)
Time frame: At baseline, 12 months, 18 months and 24 months.
MRI- affected brain region (cerebellum)
Time frame: At baseline, 12 months and 24 months.
MRI- affected brain region (spinal cord)
Time frame: At baseline, 12 months and 24 months.
MRI- affected brain region (cortical/juxtacortical)
Time frame: At baseline, 12 months and 24 months.
MRI- affected brain region (brainstem)
Time frame: At baseline, 12 months and 24 months.
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 29 Jul 2026.
- Individual participant dataSharing planned: No
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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.
Clinical Trials Unit do Centro Académico Clínico de Coimbra CTU CTU-CACC contact
Clinical Trials Unit - Coimbra Academic Clinical Center CTU CTU-CACC contact
Sonia Batista, MD, PhD principal investigator
Unidade Local de Saude de Coimbra
Irina Santos, MPSI principal investigator
University of Coimbra
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Sociocognitive rehabilitation via COGWEB platform combined with an emotional processing intervention. in people with Multiple Sclerosis, run by Sonia Batista at 2 sites in Portugal.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. 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: opening soon, as of the sponsor's last update on 29 Jul 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 Portugal. 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?
Contact Clinical Trials Unit do Centro Académico Clínico de Coimbra CTU CTU-CACC (239400400 ext. 8408, ctu-cacc@ulscoimbra.min-saude.pt), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Montreal Cognitive Assessment - MoCA (neuropsychological test) (time frame: At baseline, follow-up 12 months, 18 months and follow-up 24 months). The study lists 14 primary outcomes in all. 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 29 Jul 2026.