Transcranial Alternating Current Stimulation in Lewy Body Dementia

Condition(s) studied

Investigational drug(s) / intervention(s)

Transcranial Alternating Current Stimulation: 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: 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

Study summary

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

Primary outcome measure(s)

• Incidence of Treatment-Emergent Adverse Events of Transcranial Alternating Current Stimulation Protocol — Through study completion, at week 12
  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.
• Feasibility of Transcranial Alternating Current Stimulation Protocol — Through study completion, at week 12
  Feasibility will be assessed based on the drop-out rate. Feasibility will be monitored throughout the duration of the study.
• Mini-Mental State Examination (MMSE) — Change from baseline to week 12
  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.
• Neuropsychiatric Inventory (NPI) — Change from baseline to week 2 and 12
  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).
• Qualitive Pentagon Test — Change from baseline to week 2 and 12
  Praxis-constructive abilities will be assessed by Qualitive Pentagon Test; the subject is asked to copy two intersecting pentagons. Qualitive Pentagon Test scores range from 0 to 13, with higher scores indicating a better performance.
• Rey Auditory Verbal Learning Test (RAVLT) — Change from baseline to week 2 and 12
  Verbal memory will be assessed using the Rey Auditory Verbal Learning Test (RAVLT), including immediate recall (sum of trials), delayed recall after 15 minutes. Scores reflect the number of correctly recalled items.
• Trail Making Test (TMT - AB) — Change from baseline to week 2 and 12
  Executive function will be assessed using the Trail Making Test, including Part A (visual attention and processing speed) and Part B (task switching and cognitive flexibility). Higher completion times reflect poorer performance.
• Clock Drawing Test (CDT) — Change from baseline to week 2 and 12
  Constructional praxis abilities, mental representation skills, and visuospatial planning will be evaluated by Clock Drawing Test (CDT). CDT scores range from 0 to 15, with higher scores indicating a better performance.
• Rey-Osterrieth Complex Figure Test (ROCF) — Change from baseline to week 2 and 12
  Visuoconstructive abilities and visual memory will be assessed by Rey-Osterrieth Complex Figure. It requires the subject to copy a complex geometric figure and subsequently reproduce it from meory after a 10 minutes delay. Both tests score from 0 to 36, with higher score indicating a better performance.
• Phonemic Fluency Test — Change from baseline to week 2 and 12
  Cognitive flexibility and verbal fluency will be evalueted by Phonemic Fluency Test. Subject is asked to generate as many words as possible from a given letter within a limited time (60 seconds); higher scores indicate better perfomance.
• Semantic Fluency Test — Change from baseline to week 2 and 12
  Lexical-semantic access and executive functioning will be evalueted by Semantic Fluency Test. Subject is asked to generate as many words as possible from a given category within a limited time (60 seconds); higher scores indicate better perfomance.
• Digit Span Test — Change from baseline to week 2 and 12
  Short-term memory and working memory will be assessed respectively using the Digit Span forward and Digit Span backward. Scores reflect the maximum number of digits recalled in correct order.
• Visual Search Task — Change from baseline to week 2 and 12
  Attention and cognitive flexibility will be assessed using a Visual Search task. Participants will be instructed to identify and select a predefined target each time it appears on the screen. Performance will be quantified by the number of correct detections (hits), missed targets (omissions), and incorrect responses (errors).

Trial sites (2)

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