Lewy Body Dementia (LBD), Transcranial Alternating Current Stimulation
Conditions
Brief 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.
Interventions
DEVICETranscranial 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.
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
Sponsors
IRCCS Centro San Giovanni di Dio Fatebenefratelli
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Intervention model description
The study is a double-blind, randomised and placebo-controlled trial, participants will be randomised into two groups: group 1, participants will receive real tACS for 2 weeks; and group 2, placebo tACS 2 weeks. Each participant will receive a total of 2 weeks of intervention, with 5 sessions per week (Wednesday to Tuesday) lasting approximately 60 minutes each.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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)
Exclusion criteria
* 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Biological Markers | Change from baseline to week 2 and 12 | 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. |
| Change in electroencephalography (EEG) | Change from baseline to week 2 and 12 | 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. |
| Change in TMS-EEG | Change from baseline to week 2 and 12 | Cortical reactivity and effective connectivity will be assessed by analyzing TMS-evoked potentials, obtained from TMS-EEG coregistration after occipital cortex stimulation. |
| Basic Activities of Daily Living (BADL) | Baseline | 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. |
| Instrumental Activities of Daily Living (IADL) | Baseline | Instrumental Activities of Daily Living (IADL; range 0-8, higher scores indicating worse outcome) assesses the loss of complex instrumental acitivities. It will be evaluated as predictors of treatment efficacy and examined for associations with differential treatment response. |
| Unified Parkinson's Disease Rating Scale - Part III (UPDRS-III) | Baseline | Unified Parkinson's Disease Rating Scale - Part III (UPDRS-III; range 0-132, higher scores indicating worse outcome) assesses motor impairment. It will be evaluated as predictors of treatment efficacy and examined for associations with differential treatment response. |
| Demographic characteristics | Baseline | Demographic characteristics (age, gender, and level of education) will be evaluated as predictors of treatment efficacy and examined for associations with differential treatment response. |
Countries
Italy
Outcome results
None listed