Skip to main content
OpenTrials
Recruiting

NCT Number: NCT07438964

Non-invasive Brain Stimulation in Multiple Sclerosis Fatigue

The neurobiological basis of central fatigue in multiple sclerosis remained unclear so far. This study investigates reward-related brain mechanisms, inflammation, and their modulation by non-invasive brain stimulation using fMRI, proteomics, and clinical measures to improve future treatment of central fatigue in MS. In the study, persons suffering from relapsing-remitting MS (RRMS) with vs. without comorbid central fatigue will be included.

The study comprises five experimental visits conducted at Charité University Medicine on five consecutive days (i.e., V1 - V5) and two follow-up visits two (V6) and four (V7) weeks after V5. True or sham anodal transcranial Direct Current Stimulation (tDCS) is applied to the left dorsolateral prefrontal cortex (dlPFC) at the five visits V1 to V5. All primary and secondary outcomes are assessed at V1 and V5.

At V6 and V7, measures of central fatigue are additionally assessed via questionnaires which are send to and back from the patients via mail.

Participants of all groups will participate in all visits.

Recruiting

Interested in participating?

Request Info

Key information

Conditions

Multiple Sclerosis Autoimmune Diseases Autoimmune Diseases of the Nervous System Demyelinating Autoimmune Diseases, CNS Demyelinating Diseases Fatigue Fatigue in Multiple Sclerosis Immune System Diseases Nervous System Diseases Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Charité Campus Mitte

Berlin, State of Berlin, 10117, Germany

Location status: Recruiting

Location contact

Janina Dr. Behrens, MD

CONTACT

[email protected]

+49 30 7560921

Zoe J Mossmann, MD/PhD

SUB_INVESTIGATOR

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Men and women
  • 18 - 70 years
  • Established MS diagnosis (relapsing-remitting MS; RRMS) prior to study inclusion
  • Maximal EDSS of 4
  • Maximal disease duration 10 years
  • Existing health insurance
  • Stable or no treatment with disease modifying treatment (DMT) in last six months prior to study onset
  • Persons with RRMS and FSMC score ≥ 22 will be included in group "RRMS with fatigue"
  • Persons with RRMS and FSMC score < 22 will be included in group "RRMS without fatigue"

Exclusion criteria

  • • MRI contraindications
  • Known endocrine, immunologic, psychiatric, and neurologic disease (other than RRMS and Major Depressive Diosorder)
  • Current treatment with pharmaceuticals affecting monoaminergic functioning such as Levodopa, Amantadin, Fluoxetin, Paroxetin or antipsychotics
  • Relapse or treatment with steroids in last four weeks window prior to study onset
  • DMT other than B-cell depleting monoclonal antibodies or fumarates
  • Sleep disorder as assessed with Pittsburgh Sleep Quality Index

Treatment and study plan

tDCS of dlPFC

Device

Transcranial direct current stimulation over left dorsolateral prefrontal cortex (DLPFC) for 20 min daily over 5 consecutive days at 1200 uA

Sham Stimulation of dlPFC

Device

Sham Stimulation of the dlPFC via tDCS device for 20 minutes on 5 consecutive days

Primary outcomes

  1. Central fatigue

    Time frame: At enrolment and 4 days, two weeks and four weeks after enrolment

    Assessed with cognitive subscale of with Fatigue Scale for Motor and Cognitive Functions (FSMC): Minimum 20 points, maximum 100 points, higher values denoting worse outcome

  2. Neurobehavioral markers of effort discounting

    Time frame: At enrolment and 4 days after enrolment

    Measured in a functional MRI (fMRI) task

  3. Neurobehavioral markers of habit formation

    Time frame: At enrolment and 4 days after enrolment

    Measured in an fMRI task

  4. White matter integrity MRI measure

    Time frame: At enrolment and 4 days after enrolment

    Computed as voxel-wise quotients of T1-weighted and T2-weigted anatomical MRI brain scan parameters

  5. Brain age marker

    Time frame: At enrolment and 4 days after enrolment

    Inferred via machine learning from anatomical T1-weighted brain scan

  6. Whole-brain grey matter fraction

    Time frame: At enrolment and 4 days after enrolment

    Inferred from anatomical T1-weighted brain MRI scans

  7. Whole-brain volume of focal brain lesions

    Time frame: At enrolment and 4 days after enrolment

    Inferred from anatomical T2-weighted brain MRI scans

Secondary outcomes

  1. Change in concentration of inflammatory markers

    Time frame: At enrolment and 4 days after enrolment

    124 blood-derived inflammatory cytokine and chemokine markers determined via an inflammatory panel

  2. Change in cognitive performance

    Time frame: At enrolment and 4 days after enrolment

    Brief International Cognitive Assessment for MS (BICAMS)

  3. Complementary fatigue markers

    Time frame: At enrolment, and 4 days, two and four weeks after enrolment

    Fatigue Severity Scale (FSS), Minimum value 7, Maximum value 63, higher score denoting a worse outcome.

  4. Severity of depressive symptoms

    Time frame: At enrolment and 4 days after enrolment

    Beck Depression Inventory (BDI-II), Minimum value 0, Maximum value 63, higher values denoting worse outcome

  5. Sleep quality

    Time frame: At enrolment and 4 days after enrolment

    Pittsburgh Sleep Quality Index (PSQI), Minimum Score 0, Maximum Score 21, higher score denoting worse outcome

  6. Severity of anxiety symptoms

    Time frame: At enrolment and 4 days after enrolment

    Measured on the State-Trait Anxiety index-I (STAI-I), minimum score 20, maximum score 80, higher score denoting worse outcome

  7. Change in Fatigue severity

    Time frame: At enrolment, and 1,2,3,4 days, two and four weeks after enrolment

    Visual analogue scale of fatigue (VAS-F), minimum value 1, maximum value 10, higher score denoting worse outcome

Study contacts

Contact information is provided by the study sponsor or research team.

Janina Dr. Behrens, Dr. med.

CONTACT

[email protected]

+49 30 7560921

Martin Dr. Weygandt, PhD

CONTACT

[email protected]

Sponsors and collaborators

Lead sponsor

Charite University, Berlin, Germany

Other

Registry information

Official study title

Non-invasive Brain Stimulation for Altering Neuro-inflammatory Mediators of Central Fatigue in Multiple Sclerosis

Important dates

Study start
2026
Primary completion
2028
Study completion
2028
First posted
Feb 27, 2026
Registry last updated
Feb 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.