Interleaved TMS-fMRI for Hippocampal Stimulation: Modeling Dose-Response Relationship in Amnestic Mild Cognitive Impairment (TMS-fMRI)

May 19, 2023 updated by: Ying-hui Chou, University of Arizona
Emerging evidence indicates that dysfunction of hippocampal synaptic plasticity, which precedes neuronal degeneration during the progression of Alzheimer's disease (AD), underlies the hallmark cognitive impairment. Although there are currently no effective disease modifying treatments for AD, recent preclinical studies in animal models of AD have suggested that repetitive transcranial magnetic stimulation (rTMS) promotes hippocampal synaptic plasticity and, ultimately, improves learning and memory abilities. Interleaved TBS-MRI is a paradigm, which allows the investigators to study human brain functionality with real-time MRI, to better understand modulations of brain activity in response to the non-invasive brain stimulation, TBS. The interleaved TBSfMRI paradigm can more accurately estimated the immediate brain activity compared to the offline TBS-MRI studies in which TBS is applied outside the MRI. With this interleaved TBS-MRI approach, the investigators will be able to measure immediate changes in targeted brain activity, such as hippocampus activation, following each TBS session. This approach has created the unprecedented potential enabling the investigators to model the dose-dependent effects of TBS more accurately on brain function.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The overarching goal of this proposed project is to maximize TBS effects to non-invasive spaced TBS in MCI. For the comparison, the investigators will include cognitively normal adults. There will be a screening session plus three consecutive days including baseline outcome measures on Day 1, TMS interventions and outcome measures on Day 2, and follow-up measurements on Day 3. In this project, on Day 2, participants will receive three TBS blocks inside the MRI scanner with each TBS block separated by 30-90 minutes to enhance the possibility of maximizing the TBS effect. This will be repeated in two blocks, each with a different TMS protocol. The protocols will be in randomized order.

Study Type

Interventional

Enrollment (Anticipated)

19

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age 50-80 years
  • MCI clinical criteria: (a) self- or informant-reported cognitive complaint; (b) preserved independence in functional abilities; and (c) absence of dementia.
  • Objective cognitive impairment supported by the following measures of general cognitive function: (a) Mini-Mental State Exam (MMSE) 24-27 (inclusive); (b) Montreal Cognitive Assessment (MoCA) 18-26 (inclusive); or (c) Clinical Dementia Rating Scale score of 0.5.
  • Right handed
  • English speaking
  • Able to attend daily intervention (Monday-Friday) for 4 days
  • Not enrolled in another interventional study within 6 months prior to beginning this study

Exclusion Criteria:

  • Contraindications to transcranial magnetic stimulation (TMS) or magnetic resonance imaging (MRI)
  • Other neurological disorders (e.g. stroke, head injuries, or multiple sclerosis)
  • Untreated depression
  • Current cancer treatment or other medical problems that might independently affect cognitive function
  • Clinical Dementia Rating Scale score more than 1.0

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Active TBS-Sham TBS
Active TBS in block one, Sham TBS in block two
Device: Transcranial Magnetic Stimulation
TMS is a non-invasive brain stimulation technique. The primary aim of the study will be to verify the deliverability of the TMS effect on the hippocampus and determine which stimulation protocol is more beneficial to each participant.
Device: Transcranial Magnetic Stimulation (Sham)
TMS is a non-invasive brain stimulation technique. The primary aim of the study will be to verify the deliverability of the TMS effect on the hippocampus and determine which stimulation protocol is more beneficial to each participant. For sham, the side of the coil that does not deliver pulses will be used.
Other: Sham TBS-Active TBS
Sham TBS in block one, Active TBS in block two
Device: Transcranial Magnetic Stimulation
TMS is a non-invasive brain stimulation technique. The primary aim of the study will be to verify the deliverability of the TMS effect on the hippocampus and determine which stimulation protocol is more beneficial to each participant.
Device: Transcranial Magnetic Stimulation (Sham)
TMS is a non-invasive brain stimulation technique. The primary aim of the study will be to verify the deliverability of the TMS effect on the hippocampus and determine which stimulation protocol is more beneficial to each participant. For sham, the side of the coil that does not deliver pulses will be used.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Brain imaging data
Time Frame: Baseline
The investigators will acquire MRI images to measure structural and functional connectivity, respectively.
Baseline
Correction rate in memory association recall
Time Frame: Baseline
Memory tasks will be implemented and measure the correct rate to assess memory function.
Baseline

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Brain imaging data
Time Frame: immediately after and 24 hours after intervention
The investigators will acquire MRI images to measure structural and functional connectivity, respectively.
immediately after and 24 hours after intervention
Correction rate in memory association recall
Time Frame: immediately after and 24 hours after intervention
Memory tasks will be implemented and measure the correct rate to assess memory function.
immediately after and 24 hours after intervention

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Arizona

Collaborators

National Institute on Aging (NIA)

Investigators

  • Principal Investigator: Ying-hui Chou, ScD, University of Arizona

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2022

Primary Completion (Anticipated)

March 31, 2024

Study Completion (Anticipated)

March 31, 2024

Study Registration Dates

First Submitted

August 16, 2022

First Submitted That Met QC Criteria

August 22, 2022

First Posted (Actual)

August 25, 2022

Study Record Updates

Last Update Posted (Actual)

May 23, 2023

Last Update Submitted That Met QC Criteria

May 19, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • R21AG077153 (U.S. NIH Grant/Contract)

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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