Non-invasive Brain Stimulation in Multiple Sclerosis Fatigue

NCT07438964 | Recruiting

• 2 other identifiers: FAMS-DFGEA4/044/25
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Multiple Sclerosis; Fatigue in Multiple Sclerosis

Keywords

Transcranial direct current stimulation; Fatigue; Multiple Sclerosis

Outcome Measures

Primary Outcomes (7)

• Central fatigue

  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

  At enrolment and 4 days, two weeks and four weeks after enrolment

• Neurobehavioral markers of effort discounting

  Measured in a functional MRI (fMRI) task

  At enrolment and 4 days after enrolment

• Neurobehavioral markers of habit formation

  Measured in an fMRI task

  At enrolment and 4 days after enrolment

• White matter integrity MRI measure

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

  At enrolment and 4 days after enrolment

• Brain age marker

  Inferred via machine learning from anatomical T1-weighted brain scan

  At enrolment and 4 days after enrolment

• Whole-brain grey matter fraction

  Inferred from anatomical T1-weighted brain MRI scans

  At enrolment and 4 days after enrolment

• Whole-brain volume of focal brain lesions

  Inferred from anatomical T2-weighted brain MRI scans

  At enrolment and 4 days after enrolment

Secondary Outcomes (7)

• Change in concentration of inflammatory markers

  At enrolment and 4 days after enrolment

• Change in cognitive performance

  At enrolment and 4 days after enrolment

• Complementary fatigue markers

  At enrolment, and 4 days, two and four weeks after enrolment

• Severity of depressive symptoms

  At enrolment and 4 days after enrolment

• Sleep quality

  At enrolment and 4 days after enrolment

Study Arms (2)

tDCS Stimulation of dlPFC

ACTIVE COMPARATOR

Medical device: tDCS Stimulation over left dorsolateral prefrontal cortex (DLPFC) for 20 min daily over 5 consecutive days

Device: tDCS of dlPFC

Sham Stimulation of dlPFC

SHAM COMPARATOR

Medical device: Placebo Sham stimulation over left dorsolateral prefrontal cortex (dlPFC) for 20 min daily over 5 consecutive days

Device: Sham Stimulation of dlPFC

Interventions

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

tDCS Stimulation of dlPFC

Sham Stimulation of dlPFC DEVICE

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

Sham Stimulation of dlPFC

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women
• years
• 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"

You may not qualify if:

• 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

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead

Study Sites (1)

Charité Campus Mitte

Berlin, State of Berlin, 10117, Germany

RECRUITING

MeSH Terms

Conditions

Multiple Sclerosis; Fatigue

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

Study Officials

• Chotima Dr. Böttcher, PhD

  Max-Delbrück-Centrum Berlin

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Janina Dr. Behrens, Dr. med.

CONTACT

+49 30 7560921; janina.behrens@charite.de

Martin Dr. Weygandt, PhD

CONTACT

martin.weygandt@mdc-berlin.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 12, 2026
• First Posted: February 27, 2026
• Study Start: March 2, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Beginning three years after project end
• Access Criteria: Researchers who provide a methodologically sound proposal.

Locations

DE (1)