Repetitive Transcranial Magnetic Stimulation in Frontotemporal Lobar Degeneration
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversità degli Studi di Brescia
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 repetitive transcranial magnetic stimulation (rTMS) in patients with frontotemporal dementia (FTLD) or in asymptomatic persons at risk of FTLD (i.e., persons familiar with FTLD patients).
rTMS is a non-invasive brain stimulation technique, and has demonstrated the ability to modulate neuronal activity by applying high-frequency magnetic fields to the surface of the skull. rTMS offers a potentially effective means to influence neural networks involved in the pathogenesis of neurodegenerative diseases, with benefits that could extend beyond symptomatic relief. Its safety has been widely documented in a variety of clinical conditions, making it an ideal candidate for application in neurodegenerative diseases.
In the present study, participants will undergo the following procedures: (i) clinical and neuropsychological assessment, (ii) TMS, and (iii) blood sampling. The occurrence of adverse events will be monitored throughout the duration of the study.
The study is structured in two phases. In the first phase, double-blind, randomised and placebo-controlled, participants will be randomised into two groups: group 1, participants will receive real rTMS for 2 weeks; and group 2, placebo rTMS for 2 weeks. In the second, open-label phase, after 10 weeks, both group 1 and group 2 participants will receive real rTMS for 2 weeks. Each participant will receive a total of 4 weeks of intervention (4 weeks of real stimulation in group 1, or 2 weeks of real stimulation and 2 weeks of placebo stimulation in group 2), with 5 sessions per week (Monday to Friday) lasting approximately 30 minutes each.
Visits will take place at the beginning of the study (T00) and after 2 weeks (T02, end of the first phase), 12 weeks (T12, beginning of the second phase), 14 weeks (T14, end of the second phase), 24 weeks (T24, follow-up). During each visit, participants underwent the following procedures: (i) clinical and neuropsychological assessment, (ii) blood sampling, and (iii) TMS. 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 volunteersQualifiers
diagnosis of FTLD (bvFTD, avPPA, svPPA, CBS, or PSP)
global CDR plus NACC FTLD ≤ 1
Disqualifiers
presence of cerebrovascular disease, hydrocephalus, intracranial masses identified by MRI, history of head trauma, serious medical conditions unrelated to FTLD, history of epilepsy, and presence of electronic (e.g., pacemaker) or metallic implants in the head.
Trial design
Design model
Parallel
Treatments tested in this trial
Theta burst stimulation
Device10 sessions (5 days/week for 2 weeks) of 20 trains of 10 bursts, each containing 3 pulses at 50 Hz, applied at a frequency of 5 Hz (total pulses: 600, total duration: approx. 3 minutes); this protocol will be repeated twice within each single session.
Sham Theta burst stimulation
Device10 sessions (5 days/week for 2 weeks) of sham theta burst stimulation.The device providing Theta Burst Stimulation can be placed in the same position and turned on, creating a similar experience for the participant, without providing any neural stimulation.
Treatment groups
120 Participants
are divided into 2 treatment groupsGroup A: Real iTBS - Real iTBSExperimental treatment 1 intervention
Group B: Sham iTBS - Real iTBSSham comparator 2 interventions
Trial outcomes
Primary outcomes
1
Safety of repetitive Transcranial Magnetic Stimulation Protocol
Safety will be assessed in terms of the frequency and severity of any adverse events. Safety will be monitored throughout the duration of the study.
Time frame
Through study completion, at week 242
Feasibility of repetitive Transcranial Magnetic Stimulation Protocol
Feasibility will be assessed according to the study drop-out rate. Feasibility will be monitored throughout the duration of the study.
Time frame
Through study completion, at week 243
Effectiveness in restoring neurotransmission
Neurotransmission will be assessed by measuring changes in glutamatergic (intracortical facilitation, ICF) and GABAergic (short-interval intracortical inhibition, SICI) neurotransmission assessed indirectly through TMS.
Time frame
Through study completion, at week 24Secondary outcomes
1
Clinical effectiveness
Clinical effectiveness will be assessed by measuring changes in clinical and cognitive measures, in behavioural and neuropsychiatric symptoms, and in caregiver burden. Specifically, the following instruments will be used: Clinical Global Impression (CGI) Severity (CGI-S) and Improvement (CGI-I) and FBI.
Time frame
Change from baseline to week 2, 12, 14, 242
Biological efficacy
Biological efficacy will be assessed via blood sampling by measuring changes in neurodegeneration biomarkers: neurofilament light (NfL, measured in pg/mL); astrogliosis: Serum Glial Fibrillary Acidic Protein (GFAP, measured in pg/mL).
Time frame
Change from baseline to week 2, 12, 14, 243
Predictors of efficacy
We will assess whether demographic characteristics (age, gender, level of education), genetic traits (comparing genetic and sporadic forms of FTD), clinical phenotype (bvFTD, avPPA, svPPA, CBS, or PSP), disease severity, markers of cognitive reserve, and plasma biomarker profile are correlated with better treatment response.
Time frame
Change from baseline to week 2, 12, 14, 24Sponsors and contacts
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Source ClinicalTrials.gov