Fighting Fatigue in Multiple Sclerosis: TMS vs. tDCS Efficacy.
Multiple Sclerosis
What this study involves
The registry does not currently label this study as recruiting. Ask about its status before planning a screening visit.
- Study type
- Interventional
- Phase
- Not applicable
- Age range
- 18 years - Not specified
- Sex eligible
- All sexes
- Healthy volunteers
- Not accepted
- Participants
- 80 Estimated
These are starting points, not an eligibility decision. The research team must review the full requirements.
About the research
Multiple Sclerosis (MS) is a chronic neurological disease impacting 2.8 million individuals globally, with fatigue being its most debilitating symptom, reported by 75% of patients. Despite its prevalence, the pathophysiology of MS-related fatigue remains poorly understood, and current pharmacological treatments have limited effectiveness. This research addresses this critical gap by investigating two non-invasive brain stimulation (NIBS) techniquestranscranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS)as innovative, effective and scalable therapeutic approaches for MS fatigue.
The study employs a parallel, randomized, triple-blind, multicentric, sham-controlled design to assess and compare the short- and long-term efficacy of TMS and tDCS in addressing MS-related fatigue. 80 participants will be recruited from multiple centers in Spain and randomly assigned to one of four experimental groups: TMS, tDCS, Sham-TMS, Sham-tDCS. Each intervention will consist of 20 sessions, conducted daily from Monday to Friday, over 4 weeks. The left dorsolateral prefrontal cortex (DLPFC, F3 following the 10/20 system for EEG) was selected as the stimulation site based on its involvement in MS-related self-reported fatigue and in cognitive fatigability. For TMS experimental groups, intermittent theta-burst protocol (iTBS) will be used to increase the cortical excitability of the stimulated area. iTBS delivers a total of 600 pulses, organised into 50 Hz triplets repeated at 5 Hz, with 2second blocks of pulses, interleaved with 8 seconds of rest, repeated 20 times (total duration: 190s). The intensity of stimulation will be individually tailored based on the active motor threshold (aMT), setting it at 80% of the aMT. The sham stimulation will follow the same protocol, but using a sham coil (placebo). For tDCS experimental groups anodal tDCS will be applied (increasing cortical excitability) with the anode over the left DLPFC (F3), and the cathode over the contralateral supraorbital area. The intensity will be 2mA, and the duration of the stimulation will be 20min per session. For tDCS placebo condition, the sham option available on the device will be selected.
Primary outcomes include changes in fatigue levels measured through MS validated self-report scales (Modified Fatigue Impact Scale-MFIS; Fatigue Scale for Motor and Cognitive Functions-FSMC); secondary outcomes include depression (Beck Depression Inventory-II, BDI-II), quality of life (Multiple Sclerosis Quality of Life, MSQOL-54), functional independence (Functional Independence Measure, FIM), and cognitive fatigability (Symbol Digit Modalities Test, SDMT). All the outcomes will be assessed at baseline, at the end of the intervention, and six months after the end of the treatment (6 months follow-up).
This project promotes personalized precision medicine and innovative new treatment methods. This research is expected to expand scientific knowledge on NIBS efficacy in MS, establish evidence-based clinical practices, and set the foundation for cost-effective, patient-centered therapies. The study also addresses gender-specific responses to treatment, ensuring inclusive therapeutic strategies. Furthermore, it has the potential to benefit other neurological conditions characterized by fatigue, such as stroke, chronic fatigue syndrome or Parkinsons disease, showing significant social, clinical, and economic impact.
Who may be able to participate?
The list below is the sponsor’s full registry wording. It can include conditions, prior treatment, test results and other requirements. A match in search does not mean you qualify.
Inclusion Criteria:
- MS diagnosis (relapsing-remitting form) according to 2024 McDonald criteria.
- ≥ 18 years old
- Expanded Disability Status Scale (EDSS) 1.5-4.5
- Fatigue Severity Scale (FSS) \>4 (mean score of all items)
- No history of disease relapses in the previous 3 months
- Be able to give informed consent.
Exclusion Criteria:
- Any other neurological condition beyond MS
- Another medical situation potentially associated with fatigue (e.g. sleep apnea, chronic fatigue syndrome, arterial hypertension)
- Secondary epilepsy
- Matching the exclusion criteria for TMS or tES application (history of epilepsy, metallic inserts in the head with the exception of titanium, pacemaker, electronic prosthesis or biostimulators, electrodes in the brain or spinal cord, dermatological problems) according to international safety guidelines (Antal et al., 2017; Lefaucheur et al., 2014; 2020; Rossi et al., 2021)
- Pregnancy or possibility of pregnancy
- Alcohol or other toxic abuse in the last year
- Major psychiatric disorders (eg, schizophrenia, bipolar disorder, etc.)
- Inability to communicate or cognitive impairment
- Change in medication in the previous 4 months
Treatment, groups and participation
The registry may describe treatments and study duration without a complete visit calendar. Ask the study team for the exact schedule, procedures, risks, costs and alternatives. Keep your usual care plan unless your treating clinician tells you otherwise.
- Assignment
- Random assignment
- Masking
- Triple masked
Active TMS
iTBS applied over left prefrontal dorsolateral cortex
Device: TMS
Sham TMS
Sham iTBS applied over left prefrontal dorsolateral cortex
Device: Sham TMS
Active tDCS
tDCS applied over left prefrontal dorsolateral cortex
Device: tDCS
Sham tDCS
Sham tDCS applied over left prefrontal dorsolateral cortex
Device: Sham tDCS
TMS DEVICE
Intermitent theta burst stimulation over dorsolateral prefrontal cortex
tDCS DEVICE
Transcranial direct current stimulation over dorsolateral prefrontal cortex
Sham TMS DEVICE
Sham intermitent theta burst stimulation over dorsolateral prefrontal cortex
Sham tDCS DEVICE
Sham transcranial direct current stimulation over dorsolateral prefrontal cortex
What researchers are measuring
Outcome measures describe what is being studied. They are not proof that a treatment works.
Primary measures
Modified Fatigue Impact Scale (MFIS)
Time frame: Baseline, post-treatment (1 month), and 6 months follow-up
The MFIS is a 21-item self-report questionnaire designed to assess how fatigue impacts the daily lives of people living with Multiple Sclerosis (MS). It consists of 21 items divided into three subscales: Physical subscale (9 items)Cognitive subscale (10 items)Psychosocial subscale (2 items). Items are rated based on the patient's experiences over the past 4 weeks using a 5-point Likert scale (from 0 = "Never" to 4 = "Almost always"). Total score ranges from 0 to 84, with higher score indicating more severe fatigue.
Fatigue Scale for Motor and Cognitive Functions (FSMC)
Time frame: Baseline, post-treatment (1 month), and 6 months follow-up
It is a 20-item scale assessing two dimensions of MS-related fatigue: cognitive and motor. Patients rank statements on a scale from "Does not apply" to "Applies completely". Cut-off values were used to classify patients as experiencing mild, moderate or severe fatigue. Higher scores indicating a greater impact of fatigue.
Multiple sclerosis fatigue severity scale (MSFSS)
Time frame: Baseline, post-treatment (1 month), and 6 months follow-up
It is a 9-item (7-point Likert scale), self-report, questionnaire designed to measure the severity of fatigue and its impact on daily activities. It is one of the most widely used and validated scales for patients with Multiple Sclerosis. Higher score Indicates more severe fatigue and interference with the patient's daily responsibilities, work, or social life.
Symbol Digit Modalities Test (SDMT)
Time frame: Baseline, post-treatment (1 month), and 6 months follow-up
The SDMT measures information processing speed, visual scanning, working memory, and sustained attention. It is widely considered the gold standard for detecting and tracking cognitive impairment in patients with Multiple Sclerosis. The total score ranges from 0 to 110, with higher score indicating better cognitive performance.
Secondary measures
Multiple Sclerosis Quality of Life (MSQOL-54)
Time frame: Baseline, post-treatment (1 month), and 6 months follow-up
It is a highly comprehensive, disease-specific health-related quality of life instrument designed for patients with Multiple Sclerosis. It consists of 54 items divided into 12 distinct subscales alongside 2 single items.The 12 Subscales: Physical function, role limitations (physical), role limitations (emotional), pain, emotional well-being, energy/fatigue, health perceptions, social function, cognitive function, health distress, sexual function, and satisfaction with sexual function. Total score ranges from 0 to 100, where higher scores indicate a better quality of life.
Functional Independence Measure (FIM)
Time frame: Baseline, post-treatment (1 month), and 6 months follow-up
It is an 18-item clinician-administered assessment designed to measure a patient's level of disability and track their functional changes during rehabilitation. It quantifies how much assistance a person requires to perform essential activities of daily living safely. It is divided into two main subscales: Motor Subscale (13 items): Covers self-care, sphincter control, transfers, and locomotion; and Cognitive Subscale (5 items): Covers communication and social cognition (problem-solving, memory). Total score ranges from 18 to 126. Higher scores indicate greater functional independence.
Barther Index
Time frame: Baseline, post-treatment (1 month), and 6 months follow-up
The Barthel Index is an internationally recognized, clinician-administered or self-report rating scale used to measure a patient's performance in activities of daily living. It consists of 10 items evaluating basic self-care and mobility tasks. The 10 Items: Feeding, bathing, grooming, dressing, bowel control, bladder control, toilet use, transfers (bed to chair), mobility (on level surfaces), and stairs. Total score ranges from 0 to 100; higher scores indicate greater independence.
Selective reminding test (SRT)
Time frame: Baseline, post-treatment (1 month), and 6 months follow-up
The SRT is a highly sensitive neuropsychological verbal memory test designed to assess verbal learning and long-term memory. It is uniquely structured to differentiate between a patient's ability to store information over the long term versus their ability to retrieve it at any given moment. It is widely used to detect cognitive impairment in Multiple Sclerosis. It consists of 6 consecutive learning trials, followed by a delayed recall trial (administered 15 to 30 minutes later) and a final recognition trial. Instead of a single final number, the SRT generates multiple crucial metrics: Long-Term Storage (LTS): The number of words that have entered long-term memory.Consistent Long-Term Retrieval (CLTR): The words consistently recalled across consecutive trials without being reminded.Short-Term Storage (STS): Words recalled only after just being read. Higher scores in all indices indicate better verbal memory and learning capacity.
Spatial recall test (10/36 SPART)
Time frame: Baseline, post-treatment (1 month), and 6 months follow-up
The 10/36 SPART is a highly sensitive neuropsychological test used to evaluate visuospatial learning and long-term visual memory. It includes two different scores: immediate recall ranges from 0 to 30; and delayed recall ranges from 0 to 10. Higher scores always indicate better visuospatial memory.
Paced auditory serial addition task (PASAT)
Time frame: Baseline, post-treatment (1 month), and 6 months follow-up
The PASAT is used to assess auditory information processing speed, sustained attention, divided attention, and working memory. The final score ranges from 0 to 60, with higher scores indicate better processing speed and working memory.
Word List Generation Test (WLG)
Time frame: Baseline, post-treatment (1 month), and 6 months follow-up
The WLG is a brief, widely used verbal fluency test designed to assess a patient's spontaneous word production, executive functioning, and mental flexibility. It includes both phonemic (phonetic) and semantic (categorical) verbal fluency tasks. The final score is simply the total number of correct, unique words produced within the time limit. Higher scores indicate better verbal fluency and executive functioning.
Stroop test
Time frame: Baseline, post-treatment (1 month), and 6 months follow-up
The Stroop Test is used to evaluate executive functioning, specifically selective attention, cognitive flexibility, and processing speed. It measures a person's ability to inhibit an automatic response (reading a word) in favor of a novel, controlled response (naming the ink color). The standard clinical version consists of three separate trials, each presented on a page with columns of items:Word Page (W): Color words (e.g., RED, GREEN, BLUE) printed in black ink. The patient reads the words as fast as possible.Color Page (C): Rows of symbols (like XXXX) printed in colored ink. The patient names the ink colors as fast as possible.Color-Word Page (CW / Interference): Color words printed in conflicting ink colors (e.g., the word RED printed in BLUE ink). The patient must name the color of the ink and ignore the written word. The Interference Score indicate resistance to interferences, with higher scores indicating better cognitive control and stronger resistance to interference.
Trail making test (A and B)
Time frame: Baseline, post-treatment (1 month), and 6 months follow-up
The Trail Making Test (TMT) is a widely used neuropsychological assessment designed to evaluate visuospatial scanning, processing speed, and executive functioning (specifically cognitive flexibility and set-shifting).
Part A (TMT-A): The patient is presented with a sheet containing the numbers 1 through 25 scattered inside circles. They must draw a continuous line connecting the numbers in sequential order (1-2-3-4...). It primarily measures visual scanning, motor speed, and basic processing speed.
Part B (TMT-B): The patient is presented with numbers (1 to 13) and letters (A to L) scattered inside circles. They must draw a continuous line alternating between numbers and letters in ascending order (1-A-2-B-3-C...). It measures complex executive control, working memory, and cognitive flexibility (set-shifting).
The score for each part is the total time in seconds taken to complete the task. Lower times indicate better cognitive performance (faster speed and efficiency).
Hospital anxiety and depression scale (HADS)
Time frame: Baseline, post-treatment (1 month), and 6 months follow-up
The HADS is a widely used 14-item (rated on a 4-point Likert scale, 0 to 3) self-report questionnaire designed to screen for anxiety and depression in patients with physical medical conditions. Its primary methodological advantage is that it strictly excludes somatic symptoms (such as fatigue, pain, or sleep disturbances). This prevents a patient's physical illness-such as Multiple Sclerosis-from artificially inflating their psychological scores.
It features two independent subscales of 7 items each:HADS-A (Anxiety): Evaluates cognitive and emotional states of tension, worry, and panic.HADS-D (Depression): Heavily focused on anhedonia (the loss of the ability to enjoy things) rather than physical lethargy.
Each subscale is calculated separately and ranges from 0 to 21. Higher scores indicate worse psychological distress.
Review the complete result tables and limitations in the official record.
Open official results ↗Research locations (1)
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1 locations
UNNE Institute for Brain Stimulation. HLA Moncloa HospitalMadrid, Madrid, SpainStatus unknown
Study team and timeline
- Lead sponsor
- Universitat Oberta de Catalunya
- Study start
- Sep 8, 2026 Actual
- Primary completion
- 2029-05 Estimated
- Study completion
- 2029-09 Estimated
- First posted
- Sep 25, 2026 Actual
- Last updated
- Nov 10, 2026 Actual
Official study contacts
No central contact is listed. Check the locations and the official record.
Official study title
Fighting Fatigue in Multiple Sclerosis: A Comparative Study of Magnetic vs. Electrical Non-invasive Brain Stimulation
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Retrieved: Nov 11, 2026 · Last registry update: Nov 10, 2026