rTMS as a Treatment for PPA
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|ClinicalTrials.gov Identifier: NCT03406429|
Recruitment Status : Not yet recruiting
First Posted : January 23, 2018
Last Update Posted : January 23, 2018
The non-fluent/agrammatic (nfvPPA) and the logopenic (lvPPA) variants of Primary progressive aphasia are neurodegenerative diseases characterized by progressive word-finding difficulties and effortful speech. Efforts to slow or halt this progression have been largely unsuccessful. As such, there is a desperate need for novel treatment strategies in PPA.
Repetitive transcranial magnetic stimulation (rTMS) is a safe, non-invasive way of stimulating cortical targets in a focal and reproducible manner. Therapeutic benefits from rTMS have been demonstrated when it is applied in many sequential sessions. For example, repeated sessions of rTMS to left dlPFC is an FDA approved treatment for major depressive disorder. With respect to language, high frequency (rTMS) increases the response rate for picture naming in healthy individuals. rTMS has also been shown to improve the number of correct naming responses in patients with Alzheimer's disease. Further, in a sham controlled study, Cotelli and colleagues demonstrated that in a group of 10 nfvPPA patients high frequency rTMS over the left and right dlPFC during object and action naming tasks improved the percent of correct responses for action, but not object naming. Finally, in a sham controlled single case study, Finocchiaro et al. applied high frequency rTMS to the left inferior mid-frontal gyrus for 3 sessions consisting of five consecutive days (treatment or sham). They found a significant and lasting improvement in the patient's performance on verb production when comparing active rTMS to sham rTMS or baseline. These studies have contributed valuable insights into the potential use of rTMS in treating the language symptoms of PPA patients.
|Condition or disease||Intervention/treatment||Phase|
|Logopenic Variant Primary Progressive Aphasia Non-Fluent Primary Progressive Aphasia||Device: Active rTMS Device: SHAM rTMS||Early Phase 1|
We hope to recruit 15-20 patients with a confirmed diagnosis of either nfvPPA or lvPPA (made by a specialized clinician). Patients must have a mild to moderate language impairment and must be native English speakers. Exclusion criteria include contraindications to receiving MRI scanning or rTMS (e.g. metallic or electromagnetically activated implants, cranial mass lesions, surgical aneurysm clips), the presence of significant medical, neurological or psychiatric co-morbid symptoms and patients without study partners It will take approximately 30 weeks to complete this research study, but the exact timing will vary according to patient, investigator and equipment availability. Each patient will have a total of up to 40 study visits, but most commonly 33 visits. Greater than 33 visits will take place in the event that patients' language improves significantly following rTMS in order to test the sustainability of the improvement. Visits will take place at the MGH Martinos Center for Biomedical Imaging.
The first visit (lasting 3-4 hours) will include obtainment of informed consent, baseline assessments, and a baseline fMRI scan (which will be used for subsequent rTMS targeting). After this, PPA patients will return for four blocks of 20Hz rTMS to left dlpfc: two in which they receive active rTMS and two in which they receive sham rTMS. The following order will be used in all patients: sham-active-sham-active. During each block rTMS (active or sham) will be administered daily for 5 days (Monday through Friday). These visits will last 1 to 1.5 hours each.
Up to five language assessment visits will be performed following each block of rTMS. Typically, there will be three of these assessments, but in cases where there is improvement in language function after rTMS, patients may have up to five post-rTMS visits. These visits will be spread apart by approximately 15 days. During the first of these visits an fMRI will be performed to probe changes induced by rTMS. Scanning will include both resting-state and task fMRI acquisitions. It is estimated that these visits will last approximately 3-4 hours each.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Within-subject crossover design|
|Masking:||None (Open Label)|
|Masking Description:||Through use of SHAM rTMS stimulation|
|Official Title:||Pilot Study of Repetitive Transcranial Magnetic Stimulation in Patients With Primary Progressive Aphasia.|
|Estimated Study Start Date :||March 1, 2018|
|Estimated Primary Completion Date :||January 1, 2020|
|Estimated Study Completion Date :||January 1, 2021|
Experimental: PPA patients
All study participants will carry a diagnosis of Primary Progressive Aphasia (PPA), either the logopenic or the non-fluent variant. All participants will receive the same study interventions in a within-subject crossover design.
Device: Active rTMS
All study participants will receive two blocks of active rTMS. Each block will consist of daily sessions of 20Hz active rTMS delivered to the left dorsolateral prefrontal cortex (dlPFC) over five days (Monday through Friday).
Device: SHAM rTMS
All study participants will receive two blocks of SHAM rTMS. Each block will consist of daily sessions of 20Hz SHAM rTMS delivered to the left dorsolateral prefrontal cortex (dlPFC) over five days (Monday through Friday).
- Language Assessment Battery [ Time Frame: Through study completion, an average of 30 weeks ]This will include tests of speech production, confrontation naming, sentence completion.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03406429
|Contact: Mark C Eldaief, M.D.||(617) email@example.com|
|Contact: Samantha Krivenskyfirstname.lastname@example.org|