Transmagnetic Stimulation Pilot in Early Stage Alzheimer's Disease

Study Overview
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Brief Summary
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Alzheimer's disease (AD) is a progressive neurodegenerative condition affecting 6.2 million individuals in the United States, resulting in an annual cost of care of $305 billion. AD is functionally characterized by progressive degeneration of large-scale brain networks (LSBNs), including the default mode network (DMN) presumably from the deposition of amyloid plaques and neurofibrillary tangles. Available FDA-approved medications for AD such as donepezil and memantine offer limited benefit and modest impact on quality of life. 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 AD. We propose a pilot trial using rs-fMRI to target dysfunctional LSBNs in early stage AD.

Official Title
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A Single Arm Study of Resting State Functional Magnetic Resonance Imaging (Rs-fMRI)-Guided Theta Burst Stimulation (TBS) in Early-Stage Alzheimer's Disease (AD)

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Device: Intermittent theta burst stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Established diagnosis of Mild Cognitive Impairment (MCI)/mild AD Evidence for Central Nervous System (CNS) amyloidosis (e.g., Amyloid positron emission tomography (PET) or cerebrospinal fluid (CSF) biomarkers consistent with AD) Prior brain imaging performed Mini-Mental State Examination (MMSE) >24 Clinical Dementia Rating (CDR) Scale 0.5-1 Stable dose of cholinesterase inhibitors and memantine for at least one month Subjects are between 40-90 years of age Exclusion Criteria: Non-AD dementia including, but not limited to, Lewy body dementia, frontotemporal dementia, vascular dementia, Jakob-Creutzfeldt disease, etc. Inability to tolerate rs-fMRI Contraindication of rs-fMRI due to implants or metal Seizure disorder

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intermittent theta burst stimulation<br>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 10-12 weeks. | Device: Intermittent theta burst stimulation<br>* 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<br>* Other names: MagVenture;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in connectivity measure of the TGd parcellations. | Assessed by calculating 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. | 9 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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transmagnetic stimulation, functional MRI guided Theta Burst Stimulation, Early Stage