TMS for the Treatment of Primary Progressive Aphasia
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|ClinicalTrials.gov Identifier: NCT04188067|
Recruitment Status : Not yet recruiting
First Posted : December 5, 2019
Last Update Posted : December 5, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|Logopenic Variant Primary Progressive Aphasia Non-fluent Variant Primary Progressive Aphasia Semantic Variant Primary Progressive Aphasia||Device: ACTIVE rTMS Device: SHAM rTMS||Early Phase 1|
30 patients with a confirmed diagnosis of PPA (non-fluent PPA, logopenic PPA or semantic PPA) (made by a specialized clinician) will be recruited. Patients must have a mild to moderate language impairment and must be native English speakers. Exclusion criteria include contraindications to receiving Magnetic Resonance Imaging (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 4 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 21 study visits. Greater than 21 visits may 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 MRI scan (which will be used for subsequent rTMS targeting). After this, patients will return for two blocks of 20Hz rTMS to left dorsolateral prefrontal cortex: one in which they receive active rTMS and one in which they receive sham rTMS. Both active and sham rTMS will be delivered as high frequency stimulation (20 hertz, 20Hz). To accomplish this, an rTMS coil capable of delivering active or sham stimulation will be employed. Order of active and sham blocks will be counterbalanced across participants. During each block rTMS (active or sham) will be administered daily for 10 days (Monday through Friday). Neuropsychological testing, including thorough language evaluations, will be done before treatment, after day 1 and day 10 of rTMS treatment. Repeat MRI imaging will be performed after day 1 and day 10 of rTMS treatment. rTMS visit durations will be as follows: Monday (day 1) visit will last approximately 3-4 hours. Tuesday, Wednesday and Thursday and Friday visits (day 2 to day 9) will last approximately 1-2 hours. Friday visit (day 10) will last approximately 5 hours.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 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:||TMS in Primary Progressive Aphasia: Modulation of Brain Networks and Language|
|Estimated Study Start Date :||February 1, 2020|
|Estimated Primary Completion Date :||January 31, 2024|
|Estimated Study Completion Date :||January 31, 2024|
Experimental: PPA patients
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
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).
- Changes in Language [ Time Frame: Baseline and post treatment Day 10 ]This will include observed changes in speech production as a result of the stimulation.
- Changes in Brain Network Connectivity [ Time Frame: Baseline and post treatment Day 10 ]This will include observed changes in resting-state functional connectivity as a result of the stimulation.
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): NCT04188067
|Contact: Alexandra Touroutoglou, PhDfirstname.lastname@example.org|
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02129|
|Contact: Alexandra Touroutoglou, PhD 617-643-6348 email@example.com|