Network-guided TMS in Early Alzheimer's Disease

NCT04549155 | Completed DMC FDA Device

• 1 other identifier: Pro00106545
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

The proposed research will test a novel network-based neurostimulation approach using MRI-derived measures of brain connectivity to establish target sites for neurostimulation and test for the enhancement of memory function beyond a sham stimulation condition. This will be tested in cohort of MCI adults using network-based transcranial magnetic stimulation (TMS) to assess for behavioral improvement due to the controlled intervention. This study will provide important evidence towards the efficacy of neuromodulatory treatments for memory decline and will accelerate the discovery of potent non-invasive treatments to remediate cognitive decline in cognitively impaired older adults.

Conditions

Mild Cognitive Impairment

Outcome Measures

Primary Outcomes (3)

• Change in Episodic Memory Task Performance (accuracy and response time)

  The primary outcome measure is the difference in memory accuracy between TMS conditions (active vs. sham) on a word memory task. We will rely on a validated EM task that has shown (1) reliable activation of the Memory Success Network (MSN), and (2) reliable deficits in MCIs. During each block of the Encoding phase, participants read a list of 120 English words and perform a domain judgement (living/nonliving) during both network-based and standard TMS targets. Active and sham TMS trials are intermixed within a block. During the Retrieval phase (post-scan), participants perform a recognition memory task including a mix of old words and new words, and memory is then subsequently assessed as a function of Targeting and TMS condition.

  Baseline + 2 followup sessions on subsequent days (Day 1, Day 2, Day 3)

• Change in neurovascular reactivity, as measured by resting-state fluctuations in activity (RSFA)

  Our measure of neurovascular reactivity, resting-state fluctuations in activity (RSFA) is collected during resting- state fMRI scans, in absence of any explicit cognitive task.

  During 3 followup sessions (Day 2, Day 3, Day 4)

• Change in structural connectivity, as measured by fractional anisotropy (FA)

  Diffusion-weighted imaging data will be used to generate connectomes representing structural connections between all cortical regions in the Harvard-Oxford Atlas. For structural connection matrices, network edges are defined by the number of tractography streamlines between each pair of nodes.

  During 3 followup sessions (Day 2, Day 3, Day 4)

Study Arms (1)

Network-guided TMS

EXPERIMENTAL

The study comprises one arm of five sessions. In Day 1 (\~1.5 hr session), participants fill forms, complete a neuropsychological test battery (NIH Toolbox, NACC UDS, BDI), and provide a saliva sample to be banked for future APOE genotype determination. On Day 2 (\~1 hr session), subjects will perform an initial MRI scanning session. In this session, MRI, RSFA, DWI, and fMRI are collected so they can be used for network-based targeting. In Days 3-5 (each comprising a \~2.5 hr session) a few days later participants will undergo combined TMS-fMRI sessions. In the scanner, participants complete four fMRI runs: 2 runs using either a network-based or standard target location, counterbalanced across participants. Active and Sham TMS trials are intermixed within each run.

Device: Transcranial Magnetic Stimulation

Interventions

Transcranial Magnetic Stimulation DEVICE

Transcranial magnetic stimulation (TMS) is a noninvasive procedure that uses magnetic fields to stimulate nerve cells in the brain to improve a variety of cognitive conditions, and to probe the dynamics of normal brain function.

Also known as: TMS, rTMS

Network-guided TMS

Eligibility Criteria

• Age: 55 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Elderly: age between 55-80
• English speaking
• Willing to provide consent
• Signed HIPAA authorization
• Use of effective method of birth control for women of childbearing capacity
• Clinical Consensus for MCI

You may not qualify if:

• History of any Axis I DSM-IV disorder
• Current or past history of substance abuse or dependence (excluding nicotine)
• Women who are pregnant or breast feeding
• Intracranial implants (e.g. aneurysms clips, shunts, stimulators, cochlear implants, or electrodes), cardiac pacemakers, or vagus Nerve stimulation device
• Increased risk of seizure for any reason, including prior diagnosis of epilepsy, seizure disorder, increased intracranial pressure, or history of significant head trauma with loss of consciousness for ≥ 30 minutes.
• Neurological disorder including, but not limited to: space occupying brain lesion; any history of seizures, history of cerebrovascular accident; fainting, cerebral aneurysm,
• Dementia, Hungtington chorea; Multiple Sclerosis.
• Current use of medications known to lower the seizure threshold and/or affect working memory
• Current or past history of substance abuse or dependence (excluding nicotine)
• Women who are pregnant or breast feeding

Sponsors & Collaborators

• Duke University: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Cognitive Dysfunction

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Simon W Davis, PhD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study has two Aims, and thus two models. For Aim 1, the primary outcome measure is the difference in memory accuracy between TMS conditions, based on a mixed-effects design consisting of 4 repeated measurements per subject (2 memory conditions \[successful, unsuccessful\] x 2 TMS targeting \[network-based, standard\]). For Aim 2, the primary outcome measure comprises longitudinal changes in both memory performance, as well as brain imaging measures of functional and structural connectivity, and neurovascular change. For the behavioral estimates, we analyze the TMS Condition x Session interaction, which comprised 4 sessions of TMS with longitudinal estimates of behavior in 30 older adults.

Study Record Dates

• First Submitted: September 9, 2020
• First Posted: September 16, 2020
• Study Start: March 8, 2022
• Primary Completion: June 27, 2025
• Study Completion: June 27, 2025
• Last Updated: July 30, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)