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

NCT04176406 | Terminated Results DMC FDA Device

• 1 other identifier: Pro00065334_1
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (2)

• Acute Effect of a rTMS Session on the Performance for a Working Memory Task, as Measured by Accuracy (in Percentage)

  Accuracy (in percentage) will be assessed to evaluate the acute effect of rTMS.

  Through study completion, an average of one year

• Acute Effect of a rTMS Session on the Performance for a Working Memory Task, as Measured by Reaction Times (ms)

  Reaction times (in ms) will be assessed to evaluate the acute effect of rTMS

  Through study completion an average of one year

Study Arms (4)

rTMS over a node within the fronto-parietal network

ACTIVE COMPARATOR

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

Device: rTMS

Sham rTMS over a node within the fronto-parietal network

SHAM COMPARATOR

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

Device: Sham rTMS

rTMS over the DLPFC

ACTIVE COMPARATOR

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

Device: rTMS

Sham rTMS over the DLPFC

SHAM COMPARATOR

electrical sham coil applied over the DLPFC.

Device: Sham rTMS

Interventions

rTMS DEVICE

excitatory 5Hz rTMS will be used

rTMS over a node within the fronto-parietal network; rTMS over the DLPFC

Sham rTMS DEVICE

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

Sham rTMS over a node within the fronto-parietal network; Sham rTMS over the DLPFC

Eligibility Criteria

• Age: 55 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

MeSH Terms

Conditions

Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Results Point of Contact

• Title: Dr. Lawrence G. Appelbaum
• Organization: Duke University

greg@duke.edu

919-613-7664

Study Officials

• Lawrence G Appelbaum

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2019
• First Posted: November 25, 2019
• Study Start: November 25, 2019
• Primary Completion: February 27, 2020
• Study Completion: February 27, 2020
• Last Updated: January 27, 2021
• Results First Posted: January 11, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)