Transmagnetic Stimulation Pilot in Primary Progressive Aphasia (TMS in PPA)

A Single Arm Study of Resting State Functional Magnetic Resonance Imaging (Rs-fMRI)-Guided Theta Burst Stimulation (TBS) in Primary Progressive Aphasia (PPA)

Frontotemporal degeneration (FTD) is a non-Alzheimer's dementia that is the 2nd most common cause of dementia in the United States. FTD may present with focal language symptoms that are clinically described as primary progressive aphasia (PPA). There are two types of PPA associated with FTD-semantic variant primary progressive aphasia (SV-PPA) and nonfluent/agrammatic variant primary progressive aphasia (NFV-PPA). Both diseases are progressive neurodegenerative disease processes that compromise dominant hemisphere large scale brain network function, ultimately resulting in mutism. There are currently no FDA-approved treatments for PPA and management is mostly supportive. In combination with resting state functional MRI (rs-fMRI), transcranial magnetic stimulation (TMS) with intermittent theta burst stimulation (iTBS) offers a non-invasive alternative to pharmacotherapy in persons with PPA. In our prior studies of Alzheimer's disease (AD) and Lewy body Dementia (LBD) subjects, investigators have determined that the anterior temporal pole (area TGd and TGv) is an area that is commonly dysfunctional in dementia. The investigators have already embarked upon an fMRI guided study of iTBS in early stage Alzheimer's disease where subjects received a series of 5 treatments to distinct brain regions inclusive of area TGd. The investigators propose a case study of 3 PPA studies where rs-fMRI is applied to the large-scale language networks.

Study Overview

• Status: Completed
• Conditions: Primary Progressive Aphasia
• Intervention / Treatment: Device: Intermittent theta burst stimulation

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Saint Paul, Minnesota, United States, 55130
      • HealthPartners Neuroscience Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Established diagnosis of NFV-PPA and SV-PPA based on criteria (Gorno-Tempini et al., 2011)
2. Prior brain imaging performed
3. Mini Mental Status Exam (MMSE)>10
4. Subjects are between 40-90 years of age

Exclusion Criteria:

1. Non-FTD dementia including, but not limited to Alzheimer's, disease, Lewy body dementia, frontotemporal dementia, vascular dementia, Jakob-Creutzfeldt disease, etc.
2. Inability to tolerate rs-fMRI
3. Contraindication of rs-fMRI due to implants or metal
4. Seizure disorder

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Intermittent theta burst stimulation; All subjects will receive treatment with intermittent theta burst stimulation (iTBS). There will be a total of 5 treatments over a 2-week period. All subjects will receive iTBS to the right TGd region. TBS treatment will also be provided for two additional sites within the large-scale brain networks (LSBNs) that is found to contain the greatest number of connectivity anomalies. Total participation will be 8-10 weeks.

Device: Intermittent theta burst stimulation; MagVenture TMS Therapy with theta burst stimulation. Resting motor threshold: 80%; Number of pulses per session: 1200 pulses; Inter-train interval: 8 seconds; Pulse frequency in burst: 50 Hertz; Other Names: Transmagnetic stimulation; MagVenture

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Connectivity Measures of the Left TGd, 55b, and STV Parcellations at Baseline and Post-treatment	The difference and corresponding 95% confidence interval between follow-up and baseline connectivity measures of the TGd parcellations. Range: -1 to 1. Positive values indicate areas where connectivity is higher than healthy controls from the Human Connectome Project.	6 weeks

Collaborators and Investigators

• Sponsor: HealthPartners Institute
• Investigators: Principal Investigator: Michael H Rosenbloom, MD, HealthPartners Neurology; Principal Investigator: Kashyap Bhavani, PhD,MBBS, HealthPartners Neuroscience Research

Study record dates

Study Major Dates

• Study Start (Actual): October 2, 2023
• Primary Completion (Actual): May 3, 2024
• Study Completion (Actual): May 3, 2024

Study Registration Dates

• First Submitted: May 5, 2023
• First Submitted That Met QC Criteria: May 5, 2023
• First Posted (Actual): May 16, 2023

Study Record Updates

• Last Update Posted (Actual): June 3, 2025
• Last Update Submitted That Met QC Criteria: May 15, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: transmagnetic stimulation; functional MRI guided Theta Burst Stimulation
• Additional Relevant MeSH Terms: Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Metabolic Diseases; Neurobehavioral Manifestations; Neurocognitive Disorders; Dementia; Neurodegenerative Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Communication Disorders; Language Disorders; Speech Disorders; Frontotemporal Lobar Degeneration; Aphasia; Frontotemporal Dementia; Aphasia, Primary Progressive; Pick Disease of the Brain
• Other Study ID Numbers: A23-078

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No