Improving Learning and Memory in Portuguese Patients With Multiple Sclerosis

Testing the Efficacy of a Memory Training Program to Improve New Learning and Memory in Portuguese Patients With Multiple Sclerosis: A Randomized Clinical Trial

Deficits in memory and learning are common in Multiple Sclerosis, posing significant challenges in patients' daily lives. Cognitive rehabilitation has been shown to be effective in ameliorating these deficits, with programs such as the Modified Story Memory Technique (mSMT). In Portugal, no studies tested the efficacy of memory training programs. We aim to fill that gap by translating and developing mSMT, conducting a randomized double-blind, placebo-control, clinical trial, and, therefore, testing its efficacy through objective measures of cognitive function, and the maintenance of its benefits longitudinally. Patients with documented impairment in new learning abilities will be recruited at Centro Hospitalar Universitario São João, and randomly assigned to a memory retraining group or an active control group. Both groups will undergo baseline, immediate, and long-term follow-up assessments consisting of (1) a neuropsychological comprehensive assessment and (2) self-reported questionnaires regarding symptoms of anxiety, depression, fatigue, quality of life, and sleep. Optional enrollment in pre-post neuroimaging will also allow us to look at changes in the brain.

Study Overview

• Status: Recruiting
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Behavioral: Learning and Memory Training; Behavioral: Placebo Comparator

Detailed Description

Cognitive impairment in Multiple Sclerosis (MS) can manifest insidiously even before other neurological symptoms, with 40% to 65% of patients experiencing deficits. Long-term memory is consistently affected, with weak initial learning tending to lead to poor retrieval. Despite being invisible, cognitive problems in MS present significant challenges, as pharmacological treatments have shown limited efficacy in improving cognitive functions. Meanwhile, cognitive rehabilitation proves beneficial and meaningful among MS patients, with optimal outcomes observed at early stages.

The modified Story Memory Technique (mSMT) aims to ameliorate learning and memory deficits and has proven to be effective throughout three realms of assessment: objective cognitive abilities, daily life functioning, and neuroimaging. Its efficacy was already tested in different populations namely MS, progressive MS only, and traumatic brain injury. The mSMT involves ten individual sessions conducted twice weekly over five weeks, incorporating techniques such as imagery, context, and generalization. In the first four sessions, participants read stories for which they must create visual imagery to aid memory - imagery. In sessions 5 to 8, participants have word lists that they embed in a story and then visualize it - context. Sessions 9 and 10 apply mSMT to real-world situations (e.g., directions, to-do lists, and shopping) - generalization. Booster sessions may also be administered to maintain treatment effects over time. Previous studies have shown that memory improvements were sustained even six months after completion, highlighting its efficacy in MS. Neuroimaging studies proved the clinical utility of this intervention with significant changes in cerebral activation in regions associated with imagery and verbal learning, results considered extremely promising for the field of neurorehabilitation. Recognizing the need for cognitive rehabilitation programs adapted to Portuguese MS patients, the main objective of this project is to develop and test the efficacy of the Portuguese version of mSMT on MS patients in a hospital setting. This will be done through a Randomized Clinical Trial (RCT) throughout three realms of assessment: behavioral, neuropsychological, and neuroimaging.

Aim 1. Test the efficacy and the clinical utility of the Portuguese version of mSMT through objective measures of cognitive function and self-reported questionnaires regarding symptoms of anxiety, depression, fatigue, quality of life, and sleep. For this purpose, we will conduct a randomized double-blind, placebo-control, clinical trial in a hospital setting.

Aim 2. Assess the efficacy of this memory retraining protocol in a mildly impaired group and a moderate to severely impaired group.

Aim 3. Examine the maintenance of treatment effects longitudinally, through the inclusion of 6-month and 18-month follow-up assessments.

Aim 4. Examine the mSMT efficacy considering variables such as the previous neuropsychological profile and neuroimaging data.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Márcia França, Master's Degree; Phone Number: +351965495454; Email: marcia.franca.mf@gmail.com

Study Locations

• Portugal
  • Porto, Portugal, 4200-319
    • Recruiting
    • Centro Hospitalar Universitário de São João
    • Contact: Márcia França, Master's Degree; Phone Number: +351965495454; Email: marcia.franca.mf@gmail.com
    • Principal Investigator: Márcia França, Master's Degree

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• established diagnosis of MS, according to McDonald criteria;
• adult native Portuguese speakers;
• at least four years of education;
• free of exacerbations and use of steroids for at least one month, and no neurologic history other than MS;
• no history of major depressive disorder, schizophrenia, bipolar disorder, and no history of substance use/dependence;
• no significant visual impairment that impacts the ability to see testing materials and language comprehension as measured by the Token Test;
• impaired verbal new learning as documented by a performance of -1.0 or worse standard deviations below the mean, using age, sex and education-adjusted Portuguese norms on the Selective Reminding Test from the Brief Repeatable Battery of Neuropsychological Tests.

Exclusion Criteria:

• an exacerbation within one month;
• neurological history of head injury, stroke, seizures, or any other significant neurological history;
• patients on steroids, benzodiazepines, and/or neuroleptics;
• patients with an active diagnosis of Major Depressive Disorder, Schizophrenia, Bipolar Disorder;
• poor visual acuity, diplopia, or nystagmus;
• inability to understand directions and following one, two, and three step commands;
• and intact new learning and memory.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention Group; The intervention group will receive paper and pencil learning and memory training exercises, administered twice a week for five weeks (10 training sessions).	Behavioral: Learning and Memory Training; The intervention group will receive learning and memory retraining exercises, in order to learn how to apply two techniques: imagery and context. Paper and pencil memory retraining exercises will be administered twice a week for five weeks (10 training sessions).
Placebo Comparator: Placebo Control Group; The placebo control group will receive paper and pencil placebo memory exercises administered twice a week for five weeks (10 placebo control sessions).	Behavioral: Placebo Comparator; The placebo control group will receive paper and pencil placebo memory exercises, without learning techniques, administered twice a week for five weeks (10 placebo control sessions).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Verbal memory	Selective Reminding Test from Brief Repeatable Battery of Neuropsychological Tests (BRBN-T), with higher scores mean better outcome performance.	Four points in time: pre-treatment, immediately following treatment, 6 months and 18 months after treatment is completed.
Verbal memory	California Verbal Learning Test II from Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS), with higher scores mean better outcome performance.	Four points in time: pre-treatment, immediately following treatment, 6 months and 18 months after treatment is completed.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Self-reported Questionnaires	Hospital Anxiety and Depression Scale (HADS), a self-assessed questionnaire consisting of 14 items (0-3 Likert scale) assessing symptoms of depression (HADS-D subscale) and anxiety (HADS-A subscale).	Four points in time: pre-treatment, immediately following treatment, 6 months and 18 months after treatment is completed.
Self-reported Questionnaires	Modified Fatigue Impact Scale (MFIS), with a score range of 0-84 for each item, with the highest score indicating greater fatigue severity.	Four points in time: pre-treatment, immediately following treatment, 6 months and 18 months after treatment is completed.

Collaborators and Investigators

• Sponsor: Centro Hospitalar De São João, E.P.E.
• Collaborators: Instituto de Saude Publica da Universidade do Porto; Center of Psychology at University of Porto

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): August 1, 2028

Study Registration Dates

• First Submitted: November 15, 2024
• First Submitted That Met QC Criteria: December 4, 2024
• First Posted (Actual): December 9, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 11, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Multiple Sclerosis; Randomized Controlled Trial; Memory; Cognitive Rehabilitation
• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis; Sclerosis
• Other Study ID Numbers: CE-54-2024; 2024.05693.BDANA (Other Grant/Funding Number: Fundação para a Ciência e Tecnologia)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No