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

NCT05515952 | Completed Phase 2 Results DMC FDA Device

• 1 other identifier: R21AG077153
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Mild Cognitive Impairment

Keywords

Mild Cognitive Impairment; Transcranial Magnetic Stimulation

Outcome Measures

Primary Outcomes (1)

• Correction Rate in Memory Association Recall

  Memory tasks will be implemented and measure the correct rate to assess memory function. The scale is the Face Name Associated Memory Score, and the min/max values are 0-1. A higher score indicates a better outcome.

  Immediately after intervention day (block 1 day 2) and (block 2 day 2) vs. Baseline

Study Arms (2)

Active TBS-Sham TBS

OTHER

Active TBS in block one, Sham TBS in block two

Device: Transcranial Magnetic Stimulation; Device: Transcranial Magnetic Stimulation (Sham)

Sham TBS-Active TBS

OTHER

Sham TBS in block one, Active TBS in block two

Device: Transcranial Magnetic Stimulation; Device: Transcranial Magnetic Stimulation (Sham)

Interventions

Transcranial Magnetic Stimulation DEVICE

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.

Active TBS-Sham TBS; Sham TBS-Active TBS

Transcranial Magnetic Stimulation (Sham) DEVICE

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.

Active TBS-Sham TBS; Sham TBS-Active TBS

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

Bioscience Research Laboratory

Tucson, Arizona, 85719, 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

Results Point of Contact

• Title: Lisbeth Haaheim
• Organization: University of Arizona

lhaaheim@arizona.edu

520-626-7755

Study Officials

• Ying-hui Chou, ScD

  University of Arizona

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: August 16, 2022
• First Posted: August 25, 2022
• Study Start: November 1, 2022
• Primary Completion: March 31, 2024
• Study Completion: March 31, 2024
• Last Updated: July 29, 2025
• Results First Posted: July 29, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)