Transcranial Alternating Current Stimulation in Lewy Body Dementia

Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorIRCCS Centro San Giovanni di Dio Fatebenefratelli

About this trial

The aim of the study is to evaluate the safety, feasibility, clinical and biological efficacy, and predictors of efficacy of an intervention consisting of transcranial alternating current stimulation (tACS) in patients with Lewy Body Dementia (DLB).

In neurodegenerative diseases, like DLB, the process of neurodegeneration is accompanied by a significant alteration in oscillatory activity.

tACS is a neurophysiological method of non-invasive modulation of the excitability of the central nervous system that uses a mild electrical current. Recent studies have demonstrated the safety and efficacy of this method in modulating the natural brain oscillation frequencies underlying multiple cognitive processes, such as verbal memory, perception, and working memory. Preliminary data show that single stimulation with occipital α-tACS results in a significant improvement in visuospatial abilities and executive functions in patients wih DLB.

The study is double blind, randomised and placebo-controlled, participants will be randomised into two groups: group 1, participants will receive real tACS for 2 weeks, from Wednesday to Tuesday (5 sessions/week, lasting approximately 60 minutes each); and group 2, participants will receive placebo tACS for 2 weeks (5 sessions/week, lasting approximately 60 minutes each).

Visits will take place at the beginning of the study (T00), after 2 weeks (T02), and 12 weeks (T12, follow-up). During each visit, participants undergo the following procedures: (i) blood sampling, (ii) clinical and neuropsychological assessment, (iii) EEG, and (iv) TMS-EEG. The occurrence of adverse events will be monitored throughout the duration of the study. Specific biomarker analyses will be performed on the blood samples to study the pathophysiological mechanisms of the disease and the effect of the experimental intervention.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Male or female subjects aged over 18 at the time of signing the informed consent form;

Presence of a clinical diagnosis of Lewy body dementia according to clinical criteria (McKeith et al., 2017)

Disqualifiers

Age younger than that stated in the inclusion criteria;

Incapacity to understand;

Contraindications for tACS and TMS: patients with cardiac pacemakers and metal implants that are not compatible with electric or magnetic fields, history of epilepsy, current pregnancy (Safety questionnaire)

Trial design

Design model

Parallel

Treatments tested in this trial

  • Transcranial Alternating Current Stimulation

    Device

    10 sessions (5 days/week for 2 weeks), each consisting in the application of a tACS session (real at 3 mA) at the cortical level for a duration of 60 minutes each.

  • Sham Transcranial Alternating Current Stimulation

    Device

    10 sessions (5 days/week for 2 weeks), each consisting in the application of a sham tACS session at the cortical level for a duration of 60 minutes each. The electrode placement will be identical to that used for real stimulation. However, the electrical current will be automatically interrupted approximately 5 seconds after the start of stimulation, making it impossible for the patient to distinguish between sham and real stimulation

Treatment groups

40 Participants
are divided into 2 treatment groups
Group A: Experimental: Real tACSExperimental treatment 1 intervention
Group B: Sham Comparator: Sham tACSSham comparator 1 intervention

Trial outcomes

Primary outcomes

1

Incidence of Treatment-Emergent Adverse Events of Transcranial Alternating Current Stimulation Protocol

Safety and tolerability will be assessed in terms of incidence and severity of any adverse events. Safety and tolerability will be monitored throughout the duration of the study.

Time frame
Through study completion, at week 12
2

Feasibility of Transcranial Alternating Current Stimulation Protocol

Feasibility will be assessed based on the drop-out rate. Feasibility will be monitored throughout the duration of the study.

Time frame
Through study completion, at week 12
3

Mini-Mental State Examination (MMSE)

The global cognitive functioning will be assessed by Mini-Mental State Examination (MMSE); MMSE scores range from 0 to 30, with higher scores indicating a more preserved cognition.

Time frame
Change from baseline to week 12
4

Neuropsychiatric Inventory (NPI)

Neuropsychiatric Inventory (NPI) is designed to be a structured clinical interview about neuropsychiatric and behavioral symptoms will be assessed by; the score ranges from 0 (no symptoms) to 144 (severe symptoms).

Time frame
Change from baseline to week 2 and 12

Secondary outcomes

1

Change in Biological Markers

A venous blood draw (35 ml) will be performed at each timepoint (T0, T02, T12). The samples will be processed for serum, plasma, and DNA extraction. Neurodegeneration biomarkers will be analyzed, specifically changes in plasma neurofilament light (NfL) levels (pg/mL) will be evaluated. The plasma biomarker profile will be evaluated as a predictor of treatment efficacy and correlated with differential treatment response.

Time frame
Change from baseline to week 2 and 12
2

Change in electroencephalography (EEG)

Using resting-state electroencephalography (EEG) recorded under eyes-open and eyes-closed conditions, the investigators will assess changes in EEG alpha-band power (8-12 Hz). Alpha power will be quantified from scalp EEG recordings using spectral power analysis performed on the pre-processed EEG data.

Time frame
Change from baseline to week 2 and 12
3

Change in TMS-EEG

Cortical reactivity and effective connectivity will be assessed by analyzing TMS-evoked potentials, obtained from TMS-EEG coregistration after occipital cortex stimulation.

Time frame
Change from baseline to week 2 and 12
4

Basic Activities of Daily Living (BADL)

Basic Activities of Daily Living (BADL; range 0-6, higher scores indicating worse outcome) assesses the loss of daily self-sufficiency. It will be evaluated as predictors of treatment efficacy and examined for associations with differential treatment response.

Time frame
Baseline

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.