Repetitive Transcranial Magnetic Stimulation in Frontotemporal Lobar Degeneration (FTLD_rTMS)

December 18, 2025 updated by: Barbara Borroni, Università degli Studi di Brescia

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

120

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
    • Italy
      • Brescia, Italy, Italy, 25125
        • Recruiting
        • IRCCS Istituto Centro San Giovanni Di Dio - Fatebenefratelli Brescia
        • Principal Investigator:
          • Barbara Borroni, MD
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

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

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Real iTBS - Real iTBS
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
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.
Sham Comparator: Sham iTBS - Real iTBS
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
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.
Device: Sham Theta burst stimulation
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety of repetitive Transcranial Magnetic Stimulation Protocol
Time Frame: Through study completion, at week 24
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
Time Frame: Through study completion, at week 24
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
Time Frame: Through study completion, at week 24
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical effectiveness
Time Frame: Change from baseline to week 2, 12, 14, 24
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.
Change from baseline to week 2, 12, 14, 24
Biological efficacy
Time Frame: Change from baseline to week 2, 12, 14, 24
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).
Change from baseline to week 2, 12, 14, 24
Predictors of efficacy
Time Frame: Change from baseline to week 2, 12, 14, 24
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.
Change from baseline to week 2, 12, 14, 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Università degli Studi di Brescia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 13, 2025

Primary Completion (Estimated)

September 1, 2027

Study Completion (Estimated)

February 1, 2029

Study Registration Dates

First Submitted

December 1, 2025

First Submitted That Met QC Criteria

December 18, 2025

First Posted (Actual)

January 5, 2026

Study Record Updates

Last Update Posted (Actual)

January 5, 2026

Last Update Submitted That Met QC Criteria

December 18, 2025

Last Verified

April 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FTLD_rTMS

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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