Testing the therapeutic effects of transcranial direct current stimulation (tDCS) in semantic dementia: A double blind, sham controlled, randomized clinical trial (Preprint)
Authors: Sanches Clara , Levy Richard , Benisty Sarah , Volpe-Gillot Lisette , Habert Marie-Odile , Kas Aurélie , Ströer Sébastian , Pyatigorskaya Nadya , Kaglik Anna , Bourbon Angelina , Dubois Bruno , Migliaccio Raffaella , Valero-Cabré Antoni , Teichmann Marc 
Published: January 2019

BACKGROUND

Semantic dementia is a neurodegenerative disease that primarily affects the left anterior temporal lobe. It results in a gradual loss of conceptual knowledge resulting in anomia and impaired word comprehension which severely impact on communications abilities. There is currently no validated treatment. Transcranial stimulation has provided evidence for long-lasting language effects presumably linked to stimulation-induced neuroplasticity in post-stroke aphasia. However, studies evaluating its effects in neurodegenerative diseases as semantic dementia are still rare and evidence from double blind prospective therapeutic trials is required.

OBJECTIVE

The primary objective of the present clinical trial (STIM-SD) is to evaluate the therapeutic efficacy of a multiday transcranial direct current stimulation (tDCS) regime on language/semantic impairment in patients with semantic dementia. The study also explores the time course of potential tDCS-driven improvements and uses imaging biomarkers which could reflect stimulation-induced neuroplasticity.

METHODS

Double-blind sham-controlled randomized study using tDCS which will be applied daily during 10 days, and language/semantic and imaging assessments at 4 time-points: base-line, 3 days, 2 weeks and 4 months after the 10 stimulation sessions. Language/semantic assessments will be applied at the 4 time-points. Fluorodeoxyglucose Positron Emission tomography (FDG-PET), resting-state functional Magnetic Resonance Imaging (rs-fMRI), T1-weighted images for cortical thickness measures and white matter diffusion tensor imaging (DTI) will be applied at base-line and the two-weeks’ time-point. According to the principle of inter-hemispheric inhibition between left (language-related) and right homotopic regions we will use two potentially efficient stimulation modalities: left-anodal and right-cathodal tDCS over the anterior temporal lobes. This approach allows for comparing two stimulation strategies and aims at revealing the most beneficial strategy. Accordingly, the patient population (n=60) will be subdivided into 3 subgroups: left-anodal tDCS (n=20), right-cathodal tDCS (n=20) and sham tDCS (n=20). The stimulation duration will be sustained for 20 minutes at an intensity of 1.59 mA. It will be delivered through 25cm2 round stimulation electrodes (current density of 0.06 mA/cm2) placed over the left and right anterior temporal lobes for anodal and cathodal stimulation, respectively. A group of age, gender and education-matched healthy participants (n=20) will also be recruited and tested to provide normative values for the language/semantic tasks and imaging measures.

RESULTS

Ten patients have been screened for participation between June 2018 and December 2018, and 7 patients have been included in the study and randomized. Three patients have already completed the 4-month follow-up. Data analysis will begin once all study data are collected.

CONCLUSIONS

The study aims at assessing the efficacy of tDCS as a new therapeutic approach for language/semantic disorders in semantic dementia. A potential treatment would be easily applicable, inexpensive, and renewable when therapeutic effects disappear due to disease progression.

CLINICALTRIAL

ClinicalTrials.gov NCT03481933