Transcranial Alternating Current Stimulation, Frontotemporal Dementia (FTD)
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 Frontotemporal Dementia (FTD). In addition to typical symptoms, FTD also present alterations in brain oscillations. In animal models of neurodegeneration, restoration of oscillations via neuronal "entrainment" phenomena has demonstrated a significant reduction in toxic protein accumulation, resulting in improved cognitive function. tACS is a neurophysiological noninvasive method of neuromodulation increasingly studied for its therapeutic potential. It has been shown to safely modulate the oscillatory frequencies underlying multiple cognitive functions, including verbal memory, perception, and working memory. In light of this evidence, it is proposed to apply a single-session treatment of β-tACS stimulation in patients with FTD and to evaluate its clinical effects, oscillatory modifications by EEG, and changes in neurophysiological indices such as short intracortical inhibition (SICI) and intracortical facilitation (ICF), both compromised in the disease. The study has a cross-over design (multicenter, randomized, placebo-controlled and double-blind), with FTD patients randomly assigned to one of the two arms: i) Group 1, who will receive a real tACS session first (1h); ii) Group 2, who will instead undergo a sham tACS session (1h). In the next phase (cross-over), one week after the first phase, the groups will reverse the treatment: Group 1 will receive tACS sham and Group 2 will receive real tACS. The main objectives of the study are: \[1\] to evaluate the safety and tolerability of the single tACS treatment session; \[2\] to investigate the effects of the protocol on (short-term) cognitive performance in patients with FTD; \[3\] to verify intervention-induced changes in brain synchronization; \[4\] to evaluate changes in neurophysiological indices following treatment; and \[5\] evaluate any predictors of efficacy.
Interventions
DEVICETranscranial Alternating Current Stimulation
The session will consist of the application of a session of tACS (real at 2.5 mA) at the cortical level for a duration of 60 minutes.
Application of sham tACS session at the cortical level for a duration of 60 minutes. The electrode placement will be identical to that used for real stimulation. However, the electrical current will be automatically interrupted approximately 30 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
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Intervention model description
The study is a randomized, double-blind, cross-over study designed to evaluate the effects of tACS on cognitive performance and neurophysiological parameters.
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female subjects aged over 40 years at the time of signing the informed consent form; * Presence of a clinical diagnosis of Frontotemporal Dementia according to clinical criteria (Rascovsky et al., 2011; Gorno-Tempini et al., 2011).
Exclusion criteria
* Age younger than that stated in the inclusion criterion; * Inability to understand; * Contraindications for tACS and TMS: cardiac pacemaker carriers 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 |
|---|---|---|
| Safety and Feasibility of Transcranial Alternating Current Stimulation Protocol | Periprocedurally, an average 1 week | Safety will be assessed in terms of the frequency and severity of any adverse events, and feasibility will be assessed based on the study dropout rate. Safety and feasibility will be monitored throughout the study. |
| Phonemic Fluency Test | Immediately before and immediately after first stimulation. Immediately before and immediately after second stimulation, after a week. | 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 | Immediately before and immediately after first stimulation. Immediately before and immediately after second stimulation, after a week. | 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. |
| Trail Making Test (TMT - AB) | Immediately before and immediately after first stimulation. Immediately before and immediately after second stimulation, after a week. | 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. |
| Digit Span Test | Immediately before and immediately after first stimulation. Immediately before and immediately after second stimulation, after a week. | 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. |
| Modified Emotion Recognition Test | Immediately after first stimulation. Immediately after second stimulation, after a week. | Emotion recognition from facial expressions will be evalueted by Modified Emotion Recognition Test. Subject is asked to choose an emotion from five options for each face showed; higher scores indicate better perfomance. |
| Berg's Card Sorting Task | At the end of first stimulation. At the end of second stimulation, after a week. | Cognitive flexibility and problem solving will be assessed by Berg's Card Sorting Task. Scores reflect correct answer, errors and reaction time. |
| Go/No-Go Task | At the end of first stimulation. At the end of second stimulation, after a week. | Inhibition control will be assessed by Go/No-Go Task. Scores reflect correct targets, false alarms, misses and response speed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in electroencephalography (EEG) | Immediately before and immediately after first stimulation. Immediately before and immediately after second stimulation, after a week. | Using resting-state EEG recorded under eyes-open and eyes-closed conditions, the investigators will assess changes in EEG beta-band power (13-30 Hz). Beta power will be quantified from scalp EEG recordings using spectral power analysis performed on the pre-processed EEG data. |
| Effectiveness in restoring neurotransmission | Immediately before and immediately after first stimulation. Immediately before and immediately after second stimulation, after a week. | Neurotransmission will be assessed by measuring changes in glutamatergic (intracortical facilitation, ICF) and GABAergic (short-interval intracortical inhibition, SICI) neurotransmission assessed indirectly through TMS. |
| 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