NCT03962959

Brief Summary

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

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
97

participants targeted

Target at P50-P75 for not_applicable

Timeline
Completed

Started Oct 2020

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 14, 2019

Completed
4 months until next milestone

First Posted

Study publicly available on registry

May 24, 2019

Completed
1.4 years until next milestone

Study Start

First participant enrolled

October 21, 2020

Completed
4.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 24, 2025

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 24, 2025

Completed
Last Updated

April 13, 2026

Status Verified

April 1, 2026

Enrollment Period

4.9 years

First QC Date

January 14, 2019

Last Update Submit

April 8, 2026

Conditions

Mild Cognitive Impairment

Keywords

Mild Cognitive ImpairmentTranscranial Magnetic Stimulation

Outcome Measures

Primary Outcomes (4)

  • Brain imaging data

    The investigators will acquire MRI images to measure structural and functional connectivity, respectively.

    Baseline

  • NACC Neuropsychological batteries

    The investigators will use Neuropsychological batteries, which would calculate the Z-score, for measuring cognitions. With Z-score, the investigators can classify participants into MCI or non-MCI group.

    Baseline

  • Correction rate in memory association recall

    Memory tasks will be implemented and measure the correct rate to assess memory function.

    Baseline

  • Specimen sample

    A specimen for DNA will be collected and determine whether participants have APOE genotype.

    1 day (Only once in the beginning phase)

Secondary Outcomes (2)

  • Brain imaging data

    2 weeks after the intervention phase begin

  • Correction rate in memory association recall

    2 weeks after the intervention phase begin

Other Outcomes (6)

  • Brain imaging data

    an average of 1 month

  • Brain imaging data

    3 months after the intervention phase complete

  • NACC Neuropsychological batteries

    an average of 1 month

  • +3 more other outcomes

Study Arms (3)

Excitatory TBS

EXPERIMENTAL

Excitatory TBS

Device: TBS

Inhibitory TBS

EXPERIMENTAL

Inhibitory TBS

Device: TBS

Sham TBS

PLACEBO COMPARATOR

Sham TBS

Device: TBS

Interventions

TBSDEVICE

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.

Also known as: Theta Burst Stimulation (TBS)
Excitatory TBSInhibitory TBSSham TBS

Eligibility Criteria

Age50 Years - 85 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age 50-85 years
  • MCI clinical criteria: (a) typical comprehensive criteria (at least one cognitive test \<= -1.5 SD), or (b) Jak/Bondi criteria (2 tests within the same domain \<= -1SD or 3 tests total \<= -1SD)
  • 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

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)
  • Current cancer treatment or other medical problems that might independently affect cognitive function
  • Cognitively Normal Individuals:
  • Age 50-85 years
  • 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
  • Contraindications to transcranial magnetic stimulation (TMS) or magnetic resonance imaging (MRI)
  • Other neurological disorders (e.g. stroke, head injuries, or multiple sclerosis)
  • Current cancer treatment or other medical problems that might independently affect cognitive function
  • No dementia or impaired cognitive functioning, assessed using the NACC battery.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Bioscience Research Laboratory

Tucson, Arizona, 85719, United States

Location

MeSH Terms

Conditions

Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Cognition DisordersNeurocognitive DisordersMental Disorders

Study Officials

  • Ying-hui Chou, ScD

    University of Arizona

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 14, 2019

First Posted

May 24, 2019

Study Start

October 21, 2020

Primary Completion

September 24, 2025

Study Completion

September 24, 2025

Last Updated

April 13, 2026

Record last verified: 2026-04

Data Sharing

IPD Sharing
Will not share

Locations

US(1)