A Preliminary Sham-Controlled Theta Burst Stimulation (TBS) Study in Early-Stage Alzheimer's Disease (AD)
Trial Snapshot
- Phase
- Not Applicable
- Status
- Enrolling By Invitation
- Sponsor
- HealthPartners Institute
- Enrollment
- 6
- Locations
- 1
- Primary Endpoint
- Effect of TBS on cognition between and within subjects using Repeatable Battery for the Assessment of Neuropsychological Status Update (RBANS)
Study Overview
Brief Summary
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. Transcranial magnetic stimulation (TMS) with intermittent theta burst stimulation (iTBS) offers a non-invasive alternative to pharmacotherapy in persons with AD. We propose a case series study to compare sham with iTBS.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Single (Participant)
Eligibility Criteria
- Ages
- 40 Years to 90 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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 Status Examination (MMSE) >24
- •Clinical Dementia Rating (CDR) 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 resting state-function magnetic resonance imaging (rs-fMRI)
- •Contraindication of rs-fMRI due to implants or metal
- •Seizure disorder
Arms & Interventions
Intermittent theta burst stimulation
Subjects will receive treatment with intermittent theta burst stimulation (iTBS) with the active coil. There will be a total of 5 treatments over a 2-week period. All subjects will receive iTBS to the 8Av 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 6-9 weeks.
Intervention: Intermittent theta burst stimulation active coil (Device)
Sham device
Subjects will receive treatment with sham coil. There will be a total of 5 treatments over a 2-week period. Coil will be placed over the same region as the experimental group. Total participation will be 6-9 weeks. An open-label extension will be offered to participants that received the sham (control) treatment without further data collection.
Intervention: Sham coil (Device)
Outcomes
Primary Outcomes
Effect of TBS on cognition between and within subjects using Repeatable Battery for the Assessment of Neuropsychological Status Update (RBANS)
Time Frame: baseline, 7 weeks
Average change of RBANS total score in TMS arm compared to the average change in RBANS total score in the sham arm. Range \[-160 to 160\]. Positive comparison of TMS arm to sham arm indicates increased cognitive scores in TMS arm.
Secondary Outcomes
No secondary outcomes reported