Repetitive Transcranial Magnetic Stimulation in Frontotemporal Lobar Degeneration

NCT07316413 | Recruiting

• 1 other identifier: FTLD_rTMS
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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 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.

Conditions

FTLD; FTD; bvFTD; PPA; PSP; Cortical Basal Syndrome (CBS); rTMS; Theta Burst Stimulation

Outcome Measures

Primary Outcomes (3)

• 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.

  Through study completion, at week 24

• 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.

  Through study completion, at week 24

• 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.

  Through study completion, at week 24

Secondary Outcomes (3)

• Clinical effectiveness

  Change from baseline to week 2, 12, 14, 24

• Biological efficacy

  Change from baseline to week 2, 12, 14, 24

• Predictors of efficacy

  Change from baseline to week 2, 12, 14, 24

Study Arms (2)

Real iTBS - Real iTBS

EXPERIMENTAL

10 sessions of theta burst stimulation (5 days/week for 2 weeks) followed by an open-label 10 sessions of theta burst stimulation (5 days/week for 2 weeks)

Device: Theta burst stimulation

Sham iTBS - Real iTBS

SHAM COMPARATOR

10 sessions of sham stimulation (5 days/week for 2 weeks) followed by an open-label 10 sessions of theta burst stimulation (5 days/week for 2 weeks)

Device: Theta burst stimulation; Device: Sham Theta burst stimulation

Interventions

Theta burst stimulation DEVICE

10 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.

Real iTBS - Real iTBS; Sham iTBS - Real iTBS

Sham Theta burst stimulation DEVICE

10 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.

Sham iTBS - Real iTBS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• diagnosis of FTLD (bvFTD, avPPA, svPPA, CBS, or PSP)
• global CDR plus NACC FTLD ≤ 1

You may not qualify if:

• 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.

Sponsors & Collaborators

• Università degli Studi di Brescia: lead

Study Sites (1)

IRCCS Istituto Centro San Giovanni Di Dio - Fatebenefratelli Brescia

Brescia, Italy, 25125, Italy

RECRUITING

Related Publications (18)

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MeSH Terms

Conditions

Frontotemporal Lobar Degeneration

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; TDP-43 Proteinopathies; Neurodegenerative Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Neurocognitive Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: 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.

Study Record Dates

• First Submitted: December 1, 2025
• First Posted: January 5, 2026
• Study Start: February 13, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): February 1, 2029
• Last Updated: January 5, 2026

Record last verified: 2025-04

Locations

IT (1)