Mild Cognitive ImpairmentNCT03962959
Enhancement of Hippocampal Plasticity Using Repetitive Transcranial Magnetic Stimulation
A study testing TBS in people with Mild Cognitive Impairment, run by University of Arizona at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 50 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Mild Cognitive Impairment
- What is being tested?
- TBS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 97 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Oct 2020to 24 Sep 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Show all 11Show fewer
- 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
Who cannot join
- 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:
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Bioscience Research Laboratory
Tucson, Arizona, 85719
About this study
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.
Read more
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:
- To plan personalized non-invasive brain stimulation location by brain Imaging with Magnetic Resonance Imaging (MRI) in Mild Cognitive Impairment (MCI)
- 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.
Read the detailed description
In total, 60 participants (50-85 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.
- Brain imaging data 2) Neuropsychological data and demographic data 3) Cognitive tasks 4) Biological sample
- Conditions
- Mild Cognitive Impairment
- Being tested
- TBS
- Keywords
- Mild Cognitive Impairment, Transcranial Magnetic Stimulation
- Medical subject headings
- Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TBSDevice
Also called Theta Burst Stimulation (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.
| Study group | Role | What they receive |
|---|---|---|
| Excitatory TBS | Experimental | Excitatory TBS Receives: Device: TBS |
| Inhibitory TBS | Experimental | Inhibitory TBS Receives: Device: TBS |
| Sham TBS | Placebo comparator | Sham TBS Receives: Device: TBS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Brain imaging data
The investigators will acquire MRI images to measure structural and functional connectivity, respectively.
Measured: 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.
Measured: Baseline
Correction rate in memory association recall
Memory tasks will be implemented and measure the correct rate to assess memory function.
Measured: Baseline
Specimen sample
A specimen for DNA will be collected and determine whether participants have APOE genotype.
Measured: 1 day (Only once in the beginning phase)
Secondary outcomes (2)
Brain imaging data
The investigators will acquire MRI images to measure structural and functional connectivity, respectively.
Measured: 2 weeks after the intervention phase begin
Correction rate in memory association recall
Memory tasks will be implemented and measure the correct rate to assess memory function.
Measured: 2 weeks after the intervention phase begin
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2019
- Study start21 Oct 2020
- Primary completion24 Sep 2025
- Study completion24 Sep 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mild Cognitive ImpairmentStudies of the same condition, open and under way.
- More trials run by University of ArizonaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 97 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Arizona
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Sponsor
- Investigators
- Ying-hui Chou, ScD, Principal investigator, University of Arizona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03962959
- Sponsor's protocol ID
- 1812171968
- Other IDs
- R01AG062543
- Status last verified
- Apr 2026
- First submitted
- 14 Jan 2019
- Last updated
- 13 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Enhancement of Hippocampal Plasticity Using Repetitive Transcranial Magnetic Stimulation
- ClinicalTrials.gov ID
- NCT03962959
- Acronym / sponsor ID
- 1812171968
- Conditions
- Mild Cognitive Impairment
- Keywords
- Mild Cognitive Impairment, Transcranial Magnetic Stimulation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 97 participants (actual)
- Lead sponsor
- University of ArizonaUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 21 Oct 2020 (actual)
- Primary completion
- 24 Sep 2025 (actual)
- Study completion
- 24 Sep 2025 (actual)
- First posted
- 24 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- To plan personalized non-invasive brain stimulation location by brain Imaging with Magnetic Resonance Imaging (MRI) in Mild Cognitive Impairment (MCI)
- 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
In total, 60 participants (50-85 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.
- Brain imaging data 2) Neuropsychological data and demographic data 3) Cognitive tasks 4) Biological sample
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Excitatory TBS | Experimental | Device: TBSExcitatory TBS |
| Inhibitory TBS | Experimental | Device: TBSInhibitory TBS |
| Sham TBS | Placebo comparator | Device: TBSSham TBS |
Who may qualify
- Ages
- 50 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (8 listed)
- 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
- Contraindications to transcranial magnetic stimulation (TMS) or magnetic resonance imaging (MRI)
- Other neurological disorders (e.g. stroke, head injuries, or multiple sclerosis)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TBSAlso: Theta Burst Stimulation (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. | Device | Excitatory TBS, Inhibitory TBS, Sham TBS |
Primary outcome
Brain imaging data
Time frame: Baseline
The investigators will acquire MRI images to measure structural and functional connectivity, respectively.
NACC Neuropsychological batteries
Time frame: Baseline
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.
Correction rate in memory association recall
Time frame: Baseline
Memory tasks will be implemented and measure the correct rate to assess memory function.
Specimen sample
Time frame: 1 day (Only once in the beginning phase)
A specimen for DNA will be collected and determine whether participants have APOE genotype.
2 secondary outcomes
Brain imaging data
Time frame: 2 weeks after the intervention phase begin
Correction rate in memory association recall
Time frame: 2 weeks after the intervention phase begin
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ying-hui Chou, ScD principal investigator
University of Arizona
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing TBS in people with Mild Cognitive Impairment, run by University of Arizona at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Brain imaging data (time frame: Baseline). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2026.