Effectiveness of Home-Based Exercise and Brain Stimulation for Reducing Fatigue in Patients With Multiple Sclerosis

NCT07567989 | Enrolling By Invitation

• 1 other identifier: 2024/103.
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 3

Brief Summary

This randomized, double-blind, parallel-group clinical trial aims to assess the effectiveness of a combined intervention consisting of a home-based therapeutic exercise program and transcranial direct current stimulation (tDCS) for the management of fatigue in patients with multiple sclerosis (MS). Fatigue is one of the most disabling and prevalent symptoms in MS, significantly impacting patients' quality of life and functional independence. Participants diagnosed with MS who meet inclusion criteria will be randomized into two groups: Group 1: Home-based therapeutic exercise plus sham (placebo) tDCS Group 2: Home-based therapeutic exercise plus active tDCS The intervention will span a defined period, with tDCS sessions applied over the dorsolateral prefrontal cortex (DLPFC) using a standard montage and parameters validated in previous studies. The sham stimulation group will follow identical procedures without active current delivery, preserving blinding for participants and evaluators. The therapeutic exercise program is designed to be feasible for home implementation, targeting key domains affected in MS such as strength, endurance, balance, and mobility. Exercises will be prescribed based on individual patient assessments and progressively adjusted throughout the intervention period. Primary outcome measures will include functional capacity, evaluated through the Six-Minute Walk Test (6MWT), and fatigue levels, assessed via the Fatigue Severity Scale (FSS) and a Visual Analogue Scale (VAS) for fatigue. Secondary observations may include adherence rates to the exercise program and subjective reports of tolerability and perceived benefits. This trial seeks to explore whether combining a physical intervention (exercise) with a neuromodulation technique (tDCS) can offer additive benefits in managing fatigue, beyond what exercise alone provides. The ultimate goal is to develop accessible, non-pharmacological treatment strategies to improve daily functioning and quality of life for individuals living with multiple sclerosis.

Conditions

Multiple Sclerosis

Keywords

Multiple Sclerosis; Fatigue; Home-Based exercise; tDCS; Transcranial Direct Current Stimulation

Outcome Measures

Primary Outcomes (2)

• Change in Fatigue Severity Measured by the Fatigue Severity Scale (FSS)

  Fatigue severity will be assessed using the Fatigue Severity Scale (FSS). The primary endpoint is the percentage reduction in the FSS total score compared to baseline. A clinically meaningful improvement is defined as a reduction greater than 20% in the FSS total score (approximately 13 points). Fatigue assessments will be conducted at baseline (prior to the intervention), at 10 days after the final tDCS session, at 3 months, and at 6 months post-intervention to evaluate both immediate and sustained effects.

  Baseline (Day 0), Day 12 (10th and final tDCS session), 3 months from baseline, and 6 months from baseline

• Change in Fatigue Severity Measured by Visual Analogue Scale (VAS) for Fatigue

  Fatigue severity will be assessed using a Visual Analogue Scale (VAS) for fatigue. The primary endpoint is the change in VAS fatigue score compared to baseline. A clinically meaningful improvement is defined as a reduction of at least 2 points on the VAS. Fatigue assessments will be conducted at baseline (prior to the intervention), at 10 days after the final tDCS session, at 3 months, and at 6 months post-intervention to evaluate both immediate and sustained effect

  Baseline (Day 0), Day 12 (10th and final tDCS session), 3 months from baseline, and 6 months from baseline

Secondary Outcomes (1)

• Change in Functional Capacity Measured by the Six-Minute Walk Test (6MWT)

  Baseline (Day 0), Day 12 (10th and final tDCS session), 3 months from baseline, and 6 months from baseline

Other Outcomes (9)

• Change in Handgrip Strength Measured by Hand Dynamometry

  Baseline (Day 0), Day 12 (10th and final tDCS session), 3 months from baseline, and 6 months from baseline

• Change in Quality of Life Measured by EuroQol 5D (EQ-5D)

  Baseline (Day 0), Day 12 (10th and final tDCS session), 3 months from baseline, and 6 months from baseline

• Change in Exercise Tolerance Measured by Distance Walked in the 6-Minute Walk Test (6MWT)

  Baseline (Day 0), Day 12 (10th and final tDCS session), 3 months from baseline, and 6 months from baseline

Study Arms (2)

Exercise Plus Active tDCS

ACTIVE COMPARATOR

Participants assigned to this arm will complete a home-based therapeutic exercise program combined with active transcranial direct current stimulation (tDCS) targeting the dorsolateral prefrontal cortex (DLPFC). Stimulation parameters will follow validated protocols. Participants and outcomes assessors will be blinded to the assignment.

Behavioral: Home-Based Therapeutic Exercise Program; Device: Transcranial Direct Current Stimulation

Exercise Plus Sham tDCS

PLACEBO COMPARATOR

Participants assigned to this arm will complete a home-based therapeutic exercise program combined with sham transcranial direct current stimulation (tDCS). Sham stimulation will mimic the sensation of tDCS without delivering an active current. Participants and outcomes assessors will be blinded to the assignment.

Behavioral: Home-Based Therapeutic Exercise Program; Device: Sham tDCS

Interventions

Home-Based Therapeutic Exercise Program BEHAVIORAL

Participants will engage in a structured home-based therapeutic exercise program administered via a smartphone application. The program consists of targeted strength training, stretching routines, and proprioceptive exercises designed to address functional impairments commonly observed in individuals with multiple sclerosis. Each session will have an approximate duration of 20 to 30 minutes. Participants are required to complete a minimum of three sessions per week for the duration of the intervention phase.

Exercise Plus Active tDCS; Exercise Plus Sham tDCS

Transcranial Direct Current Stimulation DEVICE

Transcranial direct current stimulation (tDCS) targeting the left dorsolateral prefrontal cortex (DLPFC). Stimulation will be delivered using a standard electrode montage, with the anode positioned over the left DLPFC and the cathode over the contralateral supraorbital area. The stimulation parameters will include a current intensity of 1.5 mA applied for 20 minutes per session, with a ramp-up and ramp-down phase of 10 seconds each at the beginning and end of stimulation, respectively. Sessions will be conducted five days per week over a two-week period, for a total of 10 sessions.

Also known as: tDCS

Exercise Plus Active tDCS

Sham tDCS DEVICE

Participants assigned to the sham tDCS condition will receive identical electrode placement to the active tDCS group, with the anode over the left dorsolateral prefrontal cortex (DLPFC) and the cathode over the contralateral supraorbital area. The stimulation device will deliver an initial ramp-up phase of 10 seconds of actual stimulation after which no current will be delivered for 1180 seconds, and ending by a ramp-down phase of 10 seconds, The total session duration will match that of the active group (20 minutes), ensuring participant blinding. Sessions will occur five days per week over a two-week period, for a total of 10 sessions.

Also known as: Sham Transcranial Direct Current Stimulation

Exercise Plus Sham tDCS

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent
• Confirmed diagnosis of multiple sclerosis
• Presence of fatigue associated with multiple sclerosis, defined as a fatigue Visual Analogue Scale (VAS) score equal to or greater than 4
• Functional capacity sufficient to perform the Six-Minute Walk Test (6MWT), assessed by a Functional Ambulation Category (FAC) score of 3 or higher

You may not qualify if:

• Presence of any neurological, rheumatological, or other medical condition prior to the diagnosis of multiple sclerosis that could interfere with the study outcomes
• Presence of contraindications for transcranial direct current stimulation (tDCS), such as having a pacemaker, a history of epillepsy, pregnancy, implanted intracranial electrodes, defibrillator, or similar electronic devices.
• Cognitive impairment that limits the participant's ability to collaborate with study procedures.
• Any changes in physical therapy or pharmacological treatments for multiple sclerosis and/or fatigue that are not specified by the study protocol.
• Occurrence of a multiple sclerosis relapse or disease progression with functional repercussions during the study period.

Sponsors & Collaborators

• Jacobo Formigo: lead

Study Sites (3)

Complexo Hospitalario Universitario de A Coruña

A Coruña, A Coruña, 15009, Spain

Location

Complexo Hospitalario Universitario de Santiago de Compostela

Santiago de Compostela, A Coruña, 15706, Spain

Location

Complexo Hospitalario Universitario de Vigo

Vigo, Pontevedra, 36214, Spain

Location

Related Publications (4)

• Linnhoff S, Haghikia A, Zaehle T. Effects of repetitive twice-weekly transcranial direct current stimulations on fatigue and fatigability in people with multiple sclerosis. Sci Rep. 2023 Apr 11;13(1):5878. doi: 10.1038/s41598-023-32779-y.

  PMID: 37041183 BACKGROUND

• Mortezanejad M, Ehsani F, Masoudian N, Zoghi M, Jaberzadeh S. Comparing the effects of multi-session anodal trans-cranial direct current stimulation of primary motor and dorsolateral prefrontal cortices on fatigue and quality of life in patients with multiple sclerosis: a double-blind, randomized, sham-controlled trial. Clin Rehabil. 2020 Aug;34(8):1103-1111. doi: 10.1177/0269215520921506. Epub 2020 May 12.

  PMID: 32397748 BACKGROUND

• Bertoli M, Tataranni A, Porziani S, Pasqualetti P, Gianni E, Grifoni J, L'Abbate T, Armonaite K, Conti L, Cancelli A, Cottone C, Marinozzi F, Bini F, Cecconi F, Tecchio F. Effects on Corticospinal Tract Homology of Faremus Personalized Neuromodulation Relieving Fatigue in Multiple Sclerosis: A Proof-of-Concept Study. Brain Sci. 2023 Mar 29;13(4):574. doi: 10.3390/brainsci13040574.

  PMID: 37190539 BACKGROUND

• Xian C, Barbi C, Goldsworthy MR, Venturelli M, Sidhu SK. The interaction between metaplastic neuromodulation and fatigue in multiple sclerosis. J Neurol Sci. 2023 Jan 15;444:120521. doi: 10.1016/j.jns.2022.120521. Epub 2022 Dec 11.

  PMID: 36528976 BACKGROUND

MeSH Terms

Conditions

Multiple Sclerosis; Fatigue

Interventions

Transcranial Direct Current Stimulation

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques

Study Officials

• Jacobo Formigo, Dr,

  Complexo Hospitalario Universitario de A Coruña

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Consultant in Physical and Rehabilitation Medicine and Head of the Interventional Rehabilitation Section

Model Details: Randomized, double-blind, parallel assignment trial

Study Record Dates

• First Submitted: December 18, 2025
• First Posted: May 5, 2026
• Study Start: January 1, 2025
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: IPD and supporting information will be available beginning 6 months after publication of the primary results and will remain available for 5 years.
• Access Criteria: Qualified researchers with an approved proposal may request access to the de-identified IPD and supporting documents. Requests will be reviewed by the study sponsor. Data will be shared through a secure data access platform after signing a data use agreement.

Locations

ES (3)