Fatigue in Multiple Sclerosis, Multiple Sclerosis
Conditions
Keywords
Transcranial direct current stimulation, Fatigue, Multiple Sclerosis
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.
Interventions
DEVICEtDCS of dlPFC
Transcranial direct current stimulation over left dorsolateral prefrontal cortex (DLPFC) for 20 min daily over 5 consecutive days at 1200 uA
DEVICESham Stimulation of dlPFC
Sham Stimulation of the dlPFC via tDCS device for 20 minutes on 5 consecutive days
Sponsors
Charite University, Berlin, Germany
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Central fatigue | 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 |
| Neurobehavioral markers of effort discounting | At enrolment and 4 days after enrolment | Measured in a functional MRI (fMRI) task |
| Neurobehavioral markers of habit formation | At enrolment and 4 days after enrolment | Measured in an fMRI task |
| White matter integrity MRI measure | At enrolment and 4 days after enrolment | Computed as voxel-wise quotients of T1-weighted and T2-weigted anatomical MRI brain scan parameters |
| Brain age marker | At enrolment and 4 days after enrolment | Inferred via machine learning from anatomical T1-weighted brain scan |
| Whole-brain grey matter fraction | At enrolment and 4 days after enrolment | Inferred from anatomical T1-weighted brain MRI scans |
| Whole-brain volume of focal brain lesions | At enrolment and 4 days after enrolment | Inferred from anatomical T2-weighted brain MRI scans |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in concentration of inflammatory markers | At enrolment and 4 days after enrolment | 124 blood-derived inflammatory cytokine and chemokine markers determined via an inflammatory panel |
| Change in cognitive performance | At enrolment and 4 days after enrolment | Brief International Cognitive Assessment for MS (BICAMS) |
| Complementary fatigue markers | 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. |
| Severity of depressive symptoms | At enrolment and 4 days after enrolment | Beck Depression Inventory (BDI-II), Minimum value 0, Maximum value 63, higher values denoting worse outcome |
| Sleep quality | At enrolment and 4 days after enrolment | Pittsburgh Sleep Quality Index (PSQI), Minimum Score 0, Maximum Score 21, higher score denoting worse outcome |
| Severity of anxiety symptoms | 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 |
| Change in Fatigue severity | 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 |
Countries
Germany
Contacts
CONTACTJanina Dr. Behrens, Dr. med.
CONTACTMartin Dr. Weygandt, PhD
PRINCIPAL_INVESTIGATORChotima Dr. Böttcher, PhD
Max-Delbrück-Centrum Berlin
Outcome results
None listed