TMS for the Treatment of Primary Progressive Aphasia

NCT04188067 | Completed Results FDA Device

• 2 other identifiers: 2019P003391K23DC016912
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Primary Progressive Aphasia (PPA) is a progressive syndrome in the family of Alzheimer's disease and related disorders involving devastating language impairments caused by selective neurodegeneration of the brain's language network. Unfortunately, there is no treatment for PPA. An exciting possibility for treatment is non-invasive repetitive transcranial brain stimulation (rTMS), which induces electric currents in degenerating brain networks, making them in some cases more efficient. Therapeutic benefits from rTMS have been demonstrated when it is applied in many sequential sessions. For example, repeated sessions of rTMS to left dorsolateral prefrontal cortex (dlPFC) is approved by the US Food and Drug administration as a treatment for major depressive disorder. With respect to language, high frequency rTMS increases the response rate for picture naming in healthy individuals and in patients with Alzheimer's disease. Further, in a sham controlled study, Cotelli and colleagues demonstrated that in a group of 10 non-fluent PPA patients, high frequency rTMS over the left and right dlPFC improved the percent of correct responses for action naming. When rTMS was applied for five consecutive days in a sham controlled single case study, Finocchiaro and colleagues showed lasting improvements in language (up to 1 week) in a patient with non-fluent PPA. Trebbastoni and colleagues further showed the same lasting improvements in language (up to 1 week) in a patient with logopenic PPA. Recently, in a sham controlled single case study, Bereau and colleagues applied a more intense rTMS protocol for ten consecutive days and demonstrated significant linguistic improvements in a logopenic PPA patient that lasted for 1 month. These studies have contributed valuable insights into the potential use of rTMS in treating the language symptoms of PPA patients.

Conditions

Logopenic Variant Primary Progressive Aphasia; Non-fluent Variant Primary Progressive Aphasia; Semantic Variant Primary Progressive Aphasia

Outcome Measures

Primary Outcomes (2)

• Changes in Language as Measured Through the Boston Naming Test (BNT)

  The outcome is the Boston Naming Test (BNT), a 30-item naming task scored from 0 to 30. Higher scores indicate greater performance. We report the change between Baseline and after two weeks (Monday-Friday; 10 days total) of TMS stimulation post-treatment (post-treatment minus Baseline).

  Baseline and post-treatment

• Changes in Brain Network Connectivity Through a Comparison of the Strength of Resting-state Functional Connectivity Metric

  The outcome is the caudal Middle Frontal Gyrus resting-state functional connectivity z-scores, ranging between 0 (indicating no connectivity) and 1 (indicating strongest connectivity). We report the difference of functional connectivity scores between Baseline and after two weeks (Monday-Friday; 10 days total) of TMS stimulation post-treatment (post-treatment minus Baseline).

  Baseline and post treatment

Study Arms (2)

Active rTMS

EXPERIMENTAL

All study participants will carry a diagnosis of Primary Progressive Aphasia (PPA), either the logopenic, the non-fluent variant or the semantic variant. All participants will receive the same study interventions in a within-subject crossover design.

Device: Active rTMS

Sham rTMS

EXPERIMENTAL

All study participants will carry a diagnosis of Primary Progressive Aphasia (PPA), either the logopenic, the non-fluent variant or the semantic variant. All participants will receive the same study interventions in a within-subject crossover design.

Device: SHAM rTMS

Interventions

Active rTMS DEVICE

All study participants will receive one block of ACTIVE rTMS. Each block will consist of daily sessions of active rTMS delivered to the left dorsolateral prefrontal cortex over ten days (Monday through Friday).

Active rTMS

SHAM rTMS DEVICE

All study participants will receive one block of SHAM rTMS. Each block will consist of daily sessions of SHAM rTMS delivered to the left dorsolateral prefrontal cortex over ten days (Monday through Friday).

Sham rTMS

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients, age 18-90, who carry a diagnosis of either the logopenic (lvPPA), agrammatic non-fluent (nfvPPA) or semantic (svPPA) variants of Primary Progressive Aphasia (PPA). Patients must have been observed for at least one year by a specialized clinician.
• Patients must have at least mild to moderate language impairment.
• Patients must be native English speakers.
• Patients must have a study partner (e.g. spouse, sibling or adult child) who can accompany them to every study visit.

You may not qualify if:

• Any history of seizures, unexplained loss of consciousness or a first-degree family member with epilepsy.
• Any history of significant co-occurring neurological illness unrelated to neurodegeneration associated with PPA (e.g. multiple sclerosis), or significant medical problems (e.g. poorly controlled diabetes/hypertension or cancer within 5 years).
• Active symptoms of major depressive disorder, bipolar disorder, schizophrenia, substance use disorder or significant premorbid intellectual disability according to Diagnostic Statistical Manual (DSM-5) criteria.
• Magnetic Resonance Imaging (MRI) evidence of significant cerebrovascular disease, hydrocephalus or the presence of a space-occupying intra-cranial mass.
• Contraindications to MRI or repetitive transcranial magnetic stimulation (rTMS) including: cardiac pacemaker or pacemaker wires, neurostimulators, implanted pumps, metal in the body (rods, plates, screws, shrapnel, dentures, intrauterine device), surgical aneurysm clips in the head, previous neurosurgery or cochlear implants.
• In line with published Massachusetts General Hospital (MGH) Institutional Review Board (IRB) guidelines for rTMS, pregnancy must be ruled out by urine ß-Human Chorionic Gonadotropin if answers to screening questions suggest that pregnancy is possible and if female participants are premenopausal and of child-bearing age. Subjects will not be able to enroll if they are breastfeeding.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Institute on Deafness and Other Communication Disorders (NIDCD): collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02129, United States

Location

Related Publications (4)

• Cotelli M, Manenti R, Alberici A, Brambilla M, Cosseddu M, Zanetti O, Miozzo A, Padovani A, Miniussi C, Borroni B. Prefrontal cortex rTMS enhances action naming in progressive non-fluent aphasia. Eur J Neurol. 2012 Nov;19(11):1404-12. doi: 10.1111/j.1468-1331.2012.03699.x. Epub 2012 Mar 21.

  PMID: 22435956 BACKGROUND

• Finocchiaro C, Maimone M, Brighina F, Piccoli T, Giglia G, Fierro B. A case study of Primary Progressive Aphasia: improvement on verbs after rTMS treatment. Neurocase. 2006 Dec;12(6):317-21. doi: 10.1080/13554790601126203.

  PMID: 17182394 BACKGROUND

• Trebbastoni A, Raccah R, de Lena C, Zangen A, Inghilleri M. Repetitive deep transcranial magnetic stimulation improves verbal fluency and written language in a patient with primary progressive aphasia-logopenic variant (LPPA). Brain Stimul. 2013 Jul;6(4):545-53. doi: 10.1016/j.brs.2012.09.014. Epub 2012 Oct 24.

  PMID: 23122915 BACKGROUND

• Bereau M, Magnin E, Nicolier M, Berthet L, Dariel E, Ferreira S, Sylvestre G, Monnin J, Chopard G, Bouladour H, Vandel P, Haffen E. Left Prefrontal Repetitive Transcranial Magnetic Stimulation in a Logopenic Variant of Primary Progressive Aphasia: A Case Report. Eur Neurol. 2016;76(1-2):12-8. doi: 10.1159/000447399. Epub 2016 Jun 25.

  PMID: 27344155 BACKGROUND

Results Point of Contact

• Title: Dr. Alexandra Touroutoglou PhD
• Organization: Massachusetts General Hospital

ATOUROUTOGLOU@mgh.harvard.edu

6176436348

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Through use of SHAM rTMS stimulation
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Neurology

Model Details: Within-subject crossover design

Study Record Dates

• First Submitted: December 2, 2019
• First Posted: December 5, 2019
• Study Start: March 1, 2022
• Primary Completion: August 25, 2024
• Study Completion: August 25, 2024
• Last Updated: April 1, 2026
• Results First Posted: November 4, 2025

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)