Sociocognitive Intervention and Rehabilitation Program in Multiple Sclerosis

NCT07734675 | Not Yet Recruiting

• 2 other identifiers: 2025-OT-1312/25 CE
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 2

Brief 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. 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.

Conditions

Multiple Sclerosis

Keywords

Metacognition; Sociocognitive Intervention; Rehabilitation; Clinically Isolated Syndromes; Relapsing-remitting multiple sclerosis; Cognitive Impairment; Autoimmune Disease

Outcome Measures

Primary Outcomes (14)

• Montreal Cognitive Assessment - MoCA (neuropsychological test)

  Cognitive screening; Score 0-30 (0- worst outcome; 30- best outcome)

  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)

  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)

  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).

  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).

  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).

  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)

  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).

  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).

  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).

  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.

  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.

  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.

  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.

  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)

  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

Study Arms (2)

Rehabilitation Group

EXPERIMENTAL

Behavioral: Sociocognitive rehabilitation via COGWEB platform combined with an emotional processing intervention.

Control Group

NO INTERVENTION

Interventions

Sociocognitive rehabilitation via COGWEB platform combined with an emotional processing intervention. BEHAVIORAL

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.

Rehabilitation Group

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sonia Batista: lead
• Unidade Local de Saúde de Coimbra, EPE: collaborator

Study Sites (2)

Local Health Unit of Coimbra

Coimbra, Coimbra District, 3004-561, Portugal

Location

Unidade Local de Saude de Coimbra

Coimbra, Coimbra District, Portugal

Location

MeSH Terms

Conditions

Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Cognitive Dysfunction; Autoimmune Diseases

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Immune System Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• Sonia Batista, MD, PhD

  Unidade Local de Saude de Coimbra

  PRINCIPAL INVESTIGATOR

• Irina Santos, MPSI

  University of Coimbra

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Trials Unit do Centro Académico Clínico de Coimbra CTU CTU-CACC

CONTACT

239400400; ctu-cacc@ulscoimbra.min-saude.pt

Clinical Trials Unit - Coimbra Academic Clinical Center CTU CTU-CACC

CONTACT

+351 239 400 400; ctu-cacc@ulscoimbra.min-saude.pt

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator, MD, PhD

Model Details: Phase IIa randomized clinical trial, pragmatic, prospective, and single-center, with blinded outcome assessment (PROBE methodology: Prospective, Randomized, Open-label, Blinded Endpoint).

Study Record Dates

• First Submitted: July 14, 2026
• First Posted: July 29, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: July 29, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

PT (2)