TMS for the Treatment of Primary Progressive Aphasia

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

Interventions

DEVICE

Active rTMS

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).

DEVICE

SHAM rTMS

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).

Sponsors & Collaborators

• National Institute on Deafness and Other Communication Disorders (NIDCD)

  collaborator NIH

• Massachusetts General Hospital

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

90 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-03-01

Primary Completion

2024-08-25

Completion

2024-08-25

FDA Device

Yes

Countries

• United States

Study Locations