TMS for the Treatment of Primary Progressive Aphasia

Completed · Not applicable · Has a placebo group

Conditions studied: Logopenic Variant Primary Progressive Aphasia, Non-fluent Variant Primary Progressive Aphasia, Semantic Variant Primary Progressive Aphasia

In brief

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.

Key facts

Study ID

NCT04188067

Run by

Massachusetts General Hospital

People needed

10

Starts

2022-03-01

Expected to finish

2024-08-25

Last updated by the study team

2026-04-01

Who can join

Age: 18 and older, up to 90. Sex: any. Healthy volunteers: not accepted.

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.

Where it is running

• Massachusetts General Hospital — Boston, Massachusetts, United States

Full record on ClinicalTrials.gov

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