Enhancement of Hippocampal Plasticity Using Repetitive Transcranial Magnetic Stimulation

NCT ID: NCT03962959

Last Updated: 2023-12-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-10-21

Study Completion Date

2025-06-30

Brief Summary

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The ultimate goal of this study is to develop non-invasive, painless repetitive transcranial magnetic stimulation (rTMS) protocols to prevent cognitive decline in patients with mild cognitive impairment (MCI) and cognitively normal individuals at high risk of developing Alzheimer's disease (AD). Currently, 1 in 9 adults over the age of 65 have AD, which currently totals more than 5 million Americans and this number is expected to rise as high as 16 million by 2050.

MCI is a clinical syndrome that represents the gray area between healthy aging and dementia. Those with amnestic MCI (aMCI) have memory problems more severe than normal for their age and education, but their symptoms are not as severe as those of people with AD. Patients with aMCI are at high risk for AD. Notably, roughly half of those with MCI will continue to progress and convert to clinical dementia within 3 years. Alternatively, it is also worthwhile to study cognitively healthy older adults who carry genes that may increase the risk of AD. The frequency of the human APOE gene ε4 allele increases in patients with AD and the ε4 allele is also associated with an earlier age of disease onset.

Currently, there are no known therapies that can effectively modify the progression and hallmark symptoms of AD. Therefore, it is crucial to provide an early intervention in patients with aMCI to delay or prevent the progression to AD.

More specifically, this project has two specific aims:

1. To plan personalized non-invasive brain stimulation location by brain Imaging with Magnetic Resonance Imaging (MRI) in Mild Cognitive Impairment (MCI)
2. To identify potential personalized cognitive enhancement strategy (such as dosage or patterns) of Transcranial Magnetic Stimulation (TMS) in MCI.

Techniques to artificially and precisely stimulate brain tissue are increasingly recognized as valuable tools both in clinical practice and in cognitive neuroscience studies among healthy individuals and people with clinical conditions. With these practices, researchers can safely stimulate specific regions of the brain to explore causal relationships that comprise the brain's circuitry and modulate behavior.

Detailed Description

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In total, 60 participants (50-80 years old) with MCI will be recruited to participate in this trial.

Participants will be asked to receive 30 intervention sessions for three different protocols (10 sessions for each). Before and after the interventions, MRI and Cognitive tasks will be utilized again as the outcome measurements. There is a one-month interval between each protocol. Each intervention will be around half hour to an hour and each outcome measurement will take another two hours.

Each block includes:

* MRI+ Memory pre-assessment (2 hours/session)
* TMS \* 10 (10 sessions; 0.5 hours/session)
* MRI+ Memory post-assessment (2 hours/session) Participants will experience each of the three TMS protocols. The total time commitment across these sessions will be approximately 27 hours.

There will be another 2 testing sessions to evaluate intervention effects. They will be scheduled at the beginning, and 1 month after the end of the intervention sessions. All sessions will take place in the Biosciences Research Laboratories (BSLR) Building (1230 N. Cherry Ave., Tucson, AZ 85721). The schematic below outlines the components of the sessions.

The investigators will acquire the following data during components for primary outcome measures and secondary measures.

1\) Brain imaging data 2) Neuropsychological data and demographic data 3) Cognitive tasks 4) Biological sample

Conditions

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Mild Cognitive Impairment

Keywords

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Mild Cognitive Impairment Transcranial Magnetic Stimulation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Outcome Assessors

Study Groups

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Excitatory TBS

Excitatory TBS

Group Type EXPERIMENTAL

TBS

Intervention Type 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.

Inhibitory TBS

Inhibitory TBS

Group Type EXPERIMENTAL

TBS

Intervention Type 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.

Sham TBS

Sham TBS

Group Type PLACEBO_COMPARATOR

TBS

Intervention Type 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.

Interventions

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TBS

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.

Intervention Type DEVICE

Other Intervention Names

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Theta Burst Stimulation (TBS)

Eligibility Criteria

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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 weeks
* 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
Minimum Eligible Age

50 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute on Aging (NIA)

NIH

Sponsor Role collaborator

University of Arizona

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Bioscience Research Laboratory

Tucson, Arizona, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Yu-Chin Chen, M.D.

Role: CONTACT

Phone: 520-626-7755

Email: [email protected]

Ying-hui Chou, Sc.D.

Role: CONTACT

Phone: 520-626-7755

Email: [email protected]

Facility Contacts

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Lisbeth Haaheim

Role: primary

Other Identifiers

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R01AG062543

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1812171968

Identifier Type: -

Identifier Source: org_study_id