Using fMRI-guided TMS to Increase Central Executive Function in Older Adults (MCI_Sub)

NCT ID: NCT04176406

Last Updated: 2021-01-27

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-11-25
• Study Completion Date: 2020-02-27

Brief Summary

This is an administrative supplement to an existing project "Using fMRI-guided TMS to increase central executive function in older adults: NCT02767323" This award allows extending our existing fMRI-TMS paradigm to patients with a prodromal form of Alzheimer's Disease (AD) known as amnestic Mild Cognitive Impairment (MCI), and investigate the role of brain health factors in mediating the TMS-related memory performance benefits associated with communication between a network of frontoparietal brain regions in these populations.

The focus on focal neurostimulation at only a single site represents a fundamental gap in the approach of memory-based neurostimulation therapies. Neurostimulation affects multiple sites within a cortical network, but these global effects have not been used as targets for stimulation because of limited knowledge about what influence these localized sites have on global changes in brain state. To address this problem, multimodal neuroimaging tools and network modeling approaches developed though the parent U01 project will be used, to demonstrate how focal neurostimulation improves the efficacy of TMS for enhancing memory function. These goals will be addressed in the Administrative Supplement under our two specific aims. First, network-guided TMS will be applied to optimize memory success based in the frontoparietal network (FPN) in a new group of MCI patients. A new form of TMS targeting that involves modeling of the global network to understand how the controllability of a stimulation site evokes changes in widespread brain networks will be tested. Second, structural and functional factors affecting the efficacy of individualized network-guided TMS will be identified to ameliorate deficits in MCI. By creating a multimodal model of neural deficits related to MCI, network-guided TMS will be adjusted to demonstrate how the MCI brain might compensate for these neural deficits. The parent U01 project has made foundational advances towards these goals, as we have demonstrated the ability of to selectively enhance and reduce working memory performance in healthy older adults. In the current Administrative Supplement this paradigm will be extended to a group of MCI participants in order to test the hypothesis that excitatory rTMS to the working memory network can provide positive outcomes for patients with pre-clinical AD. The proposed work will provide an important tool for studying the stability and controllability of network connectivity of memory states in the aging brain, as well as new information on the effectiveness of brain stimulation technologies as a therapeutic approach for cognitive decline.

Conditions

Mild Cognitive Impairment

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

rTMS over a node within the fronto-parietal network

excitatory 5Hz rTMS will be applied over a node within the fronto-parietal network, defined via network analysis.

Group Type: ACTIVE_COMPARATOR

rTMS

Intervention Type: DEVICE

excitatory 5Hz rTMS will be used

Sham rTMS over a node within the fronto-parietal network

electrical sham coil applied over a node within the fronto-parietal network.

Group Type: SHAM_COMPARATOR

Sham rTMS

Intervention Type: DEVICE

an electrical sham coil reproducing the same clicking sound and tactile sensation than the active rTMS will be used

rTMS over the DLPFC

excitatory 5Hz rTMS will be applied over the dorso-lateral prefrontal cortex showing the strongest fMRI activation.

Group Type: ACTIVE_COMPARATOR

rTMS

Intervention Type: DEVICE

excitatory 5Hz rTMS will be used

Sham rTMS over the DLPFC

electrical sham coil applied over the DLPFC.

Group Type: SHAM_COMPARATOR

Sham rTMS

Intervention Type: DEVICE

an electrical sham coil reproducing the same clicking sound and tactile sensation than the active rTMS will be used

Interventions

rTMS

excitatory 5Hz rTMS will be used

Intervention Type: DEVICE

Sham rTMS

an electrical sham coil reproducing the same clicking sound and tactile sensation than the active rTMS will be used

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• English Speaking
• willing to provide consent
• signed HIPAA authorization

Exclusion Criteria

• History of any I DSM IV disorder that is unstable or untreated
• 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
• increased risk of seizure for any reason, including prior diagnosis of epilepsy, seizure disorder, increased intracranial pressure, or history of significant head trauma greater than mild concussion (History of significant head trauma, including with loss of consciousness for ≥ 30 minutes, alteration of consciousness for up to 24 hours following the event, or post-traumatic amnesia) in the past 10yrs or head injury received after age 65
• Neurological disorder including, but not limited to: space occupying brain lesion; any history of seizures, history of cerebrovascular accident; cerebral aneurysm , Dementia, Huntington chorea, multiple sclerosis
• Increased risk of seizure for any reason, including prior diagnosis of increased intracranial pressure (such as after large infarctions or trauma), or currently taking medication that are on the strong potential hazard list for rTMS.
• Subjects taking medications with an ACB score of 3.

• Minimum Eligible Age: 55 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute on Aging (NIA)

NIH

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lawrence G Appelbaum

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

Duke University Medical Center

Durham, North Carolina, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

Pro00065334_1

Identifier Type: -

Identifier Source: org_study_id