Non-invasive Brain Stimulation in Multiple Sclerosis Fatigue

Charite University, Berlin, Germany84 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Multiple Sclerosis Fatigue in Multiple Sclerosis

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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

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

Neurobehavioral markers of effort discounting

Measured in a functional MRI (fMRI) task