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

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.

Study Overview

• Status: Terminated
• Conditions: Mild Cognitive Impairment
• Intervention / Treatment: Device: rTMS; Device: Sham rTMS

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• English Speaking
• willing to provide consent
• signed HIPAA authorization
• clinical consensus for MCI; and/or met inclusion criterial on MoCA, ApoE.

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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.	Device: rTMS; excitatory 5Hz rTMS will be used
Sham Comparator: Sham rTMS over a node within the fronto-parietal network; electrical sham coil applied over a node within the fronto-parietal network.	Device: Sham rTMS; an electrical sham coil reproducing the same clicking sound and tactile sensation than the active rTMS will be used
Active Comparator: rTMS over the DLPFC; excitatory 5Hz rTMS will be applied over the dorso-lateral prefrontal cortex showing the strongest fMRI activation.	Device: rTMS; excitatory 5Hz rTMS will be used
Sham Comparator: Sham rTMS over the DLPFC; electrical sham coil applied over the DLPFC.	Device: Sham rTMS; an electrical sham coil reproducing the same clicking sound and tactile sensation than the active rTMS will be used

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: National Institute on Aging (NIA)
• Investigators: Principal Investigator: Lawrence G Appelbaum, Duke University

Study record dates

Study Major Dates

• Study Start (Actual): November 25, 2019
• Primary Completion (Actual): February 27, 2020
• Study Completion (Actual): February 27, 2020

Study Registration Dates

• First Submitted: November 20, 2019
• First Submitted That Met QC Criteria: November 21, 2019
• First Posted (Actual): November 25, 2019

Study Record Updates

• Last Update Posted (Actual): January 27, 2021
• Last Update Submitted That Met QC Criteria: January 8, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction
• Other Study ID Numbers: Pro00065334_1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No