Prodromal Alzheimer's DiseaseNCT06956300
TMS for Cognitive Decline in Aging and Preclinical AD
A study testing Active rTMS in people with Prodromal Alzheimer's Disease and Preclinical Alzheimer's Disease, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
In this research study we want to learn more about the effects of non-invasive brain stimulation on motivation, memory, and brain-network function in cognitively unimpaired older adults and individuals with preclinical Alzheimer's disease. Read more about this study
- Who is it for?
- Ages 40 to 99 yearsHealthy volunteers can take part
- Conditions the study is for
- Prodromal Alzheimer's Disease, Preclinical Alzheimer's Disease, Healthy Aging
- What is being tested?
- Active rTMS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Apr 2025to 31 Aug 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 40 to 99 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Between the ages of 40-99
- Native English speakers
- Willing and able to consent to the protocol and undergo imaging and neuropsychological testing at the specified time points
- Cognitively normal older adults and individuals with preclinical Alzheimer's disease will be included.
Who cannot join
- History of head trauma involving loss of consciousness or alteration in consciousness
- Another major neurologic or psychiatric condition
- Known presence of a structural brain lesion (e.g. tumor, cortical infarct)
- Any contraindication to MRI, such as presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments, or foreign objects in the eyes, skin, or body
- Longstanding premorbid history (i.e. longer than 10 years) of alcohol or substance abuse with continuous abuse up to and including the time that the symptoms leading to clinical presentation developed
- Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the study protocol.
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- Unwilling to return for follow-up, undergo neuropsychological testing, TMS, and MR imaging
- History of unprovoked seizures (i.e., seizures that occur in the absence of a clear provocation such as hyponatremia, hypoglycemia, etc.).
- Subjects who have a first degree relative (e.g., father, mother or sibling) with a seizure disorder.
- Subjects currently taking, or plan to take, medications which are highly epileptogenic. These include: clozapine, high doses of bupropion (i.e., greater than 400mg daily), diphenhydramine, cyclosporine, isoniazid, imipenem, chloroquine, tramadol and theophylline.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02129
Alexandra Touroutoglou, MSc, PhD, 617-643-6348, atouroutoglou@mgh.harvard.edu
Alexandra Touroutoglou, MSc, PhD
About this study
Official title: Grit Against Cognitive Decline in Aging and Preclinical Alzheimer's Disease
In this research study we want to learn more about the effects of non-invasive brain stimulation on motivation, memory, and brain-network function in cognitively unimpaired older adults and individuals with preclinical Alzheimer's disease.
This study will use a form of non-invasive brain stimulation called repetitive Transcranial Magnetic Stimulation (rTMS). rTMS will slightly alter activity in an area of your brain that controls cognition. Changes resulting from this stimulation will be measured with behavioral tests, as well as by taking brain images with Magnetic Resonance Imaging (MRI).
Participants will come in for one baseline visit followed by 10 days of daily rTMS study visits (Monday through Friday) and an evaluation visit. Then, there will be a 2-week break. After this break, they will return for another baseline visit, an additional 10 days of rTMS, and a final evaluation visit.
- Conditions
- Prodromal Alzheimer's Disease, Preclinical Alzheimer's Disease, Healthy Aging, Cognitive Decline
- Being tested
- Active rTMS, Sham rTMS
- Keywords
- 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.
Active rTMSDevice
All study participants will receive one block of ACTIVE rTMS. Each block will consist of daily sessions of active rTMS delivered to the left dorsolateral prefrontal cortex over ten days (Monday through Friday).
Sham rTMSDevice
All study participants will receive one block of SHAM rTMS. Each block will consist of daily sessions of SHAM rTMS delivered to the left dorsolateral prefrontal cortex over ten days (Monday through Friday).
| Study group | Role | What they receive |
|---|---|---|
| Active TMS | Experimental | All participants will receive the same study interventions in a within-subject crossover design. Receives: Device: Active rTMS |
| Sham TMS | Sham comparator | All participants will receive the same study interventions in a within-subject crossover design. Receives: Device: Sham rTMS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in motivation
This will be measured by ratings of grit on a 5-point scale using the Grit Scale (Duckworth, et al., 2007).
Measured: Baseline and post-treatment Day 11
Changes in Brain Network Connectivity
This will include changes in resting-state functional connectivity measured with functional Magnetic Resonance Imaging (fMRI)
Measured: Baseline and post-treatment Day 11
Changes in Memory
This will be measured with an associative memory task
Measured: Baseline and Post-Treatment Day 11
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2025
- Study start7 Apr 2025
- Primary completion31 Aug 2029 (estimated)
- Study completion31 Aug 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prodromal Alzheimer's DiseaseStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe 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
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Alexandra Touroutoglou, Harvard Medical School (HMS and HSDM)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06956300
- Sponsor's protocol ID
- 2023A009489
- Status last verified
- Feb 2026
- First submitted
- 14 Apr 2025
- Last updated
- 20 Feb 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 20 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Grit Against Cognitive Decline in Aging and Preclinical Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT06956300
- Acronym / sponsor ID
- 2023A009489
- Conditions
- Prodromal Alzheimer's Disease, Preclinical Alzheimer's Disease, Healthy Aging, Cognitive Decline
- Keywords
- Transcranial Magnetic Stimulation
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- 7 Apr 2025 (actual)
- Primary completion
- 31 Aug 2029 (estimated)
- Study completion
- 31 Aug 2029 (estimated)
- First posted
- 4 May 2025 (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.
In this research study we want to learn more about the effects of non-invasive brain stimulation on motivation, memory, and brain-network function in cognitively unimpaired older adults and individuals with preclinical Alzheimer's disease.
This study will use a form of non-invasive brain stimulation called repetitive Transcranial Magnetic Stimulation (rTMS). rTMS will slightly alter activity in an area of your brain that controls cognition. Changes resulting from this stimulation will be measured with behavioral tests, as well as by taking brain images with Magnetic Resonance Imaging (MRI).
Participants will come in for one baseline visit followed by 10 days of daily rTMS study visits (Monday through Friday) and an evaluation visit. Then, there will be a 2-week break. After this break, they will return for another baseline visit, an additional 10 days of rTMS, and a final evaluation visit.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active TMS | Experimental | Device: Active rTMSAll participants will receive the same study interventions in a within-subject crossover design. |
| Sham TMS | Sham comparator | Device: Sham rTMSAll participants will receive the same study interventions in a within-subject crossover design. |
Who may qualify
- Ages
- 40 to 99 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Between the ages of 40-99
- Native English speakers
- Willing and able to consent to the protocol and undergo imaging and neuropsychological testing at the specified time points
- Cognitively normal older adults and individuals with preclinical Alzheimer's disease will be included.
Key exclusion criteria (10 listed)
- History of head trauma involving loss of consciousness or alteration in consciousness
- Another major neurologic or psychiatric condition
- Known presence of a structural brain lesion (e.g. tumor, cortical infarct)
- Any contraindication to MRI, such as presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments, or foreign objects in the eyes, skin, or body
- Longstanding premorbid history (i.e. longer than 10 years) of alcohol or substance abuse with continuous abuse up to and including the time that the symptoms leading to clinical presentation developed
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 |
|---|---|---|
| Active rTMSAll study participants will receive one block of ACTIVE rTMS. Each block will consist of daily sessions of active rTMS delivered to the left dorsolateral prefrontal cortex over ten days (Monday through Friday). | Device | Active TMS |
| Sham rTMSAll study participants will receive one block of SHAM rTMS. Each block will consist of daily sessions of SHAM rTMS delivered to the left dorsolateral prefrontal cortex over ten days (Monday through Friday). | Device | Sham TMS |
Primary outcome
Changes in motivation
Time frame: Baseline and post-treatment Day 11
This will be measured by ratings of grit on a 5-point scale using the Grit Scale (Duckworth, et al., 2007).
Changes in Brain Network Connectivity
Time frame: Baseline and post-treatment Day 11
This will include changes in resting-state functional connectivity measured with functional Magnetic Resonance Imaging (fMRI)
Changes in Memory
Time frame: Baseline and Post-Treatment Day 11
This will be measured with an associative memory task
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2026.
- Individual participant dataSharing planned: No
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Active rTMS in people with Prodromal Alzheimer's Disease and Preclinical Alzheimer's Disease, run by Massachusetts General Hospital 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 4 inclusion and 10 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: looking for participants now, as of the sponsor's last update on 20 Feb 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Alexandra Touroutoglou, PhD (6176436348, atouroutoglou@mgh.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in motivation (time frame: Baseline and post-treatment Day 11). The study lists 3 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 20 Feb 2026; AzTrials last refreshed its copy on 5 Nov 2026.