Recruiting

Phase 1

Phase 2

rTMSLarge-coil Parietal Repetitive Transcranial Magnetic Stimulation (rTMS) for Alzheimer Disease (AD)

Sponsor:

UCLA

Code:

NCT06597942

Conditions

Alzheimer&Amp;Amp;#39;s Disease

Alzheimer Disease

Dementia Alzheimer Type

Mild Alzheimer&Amp;Amp;#39;s Disease

Moderate Alzheimer&Amp;Amp;#39;s Disease

Eligibility Criteria

Sex: All

Age: 55 - 70+

Healthy Volunteers: Not accepted

Interventions

TMS

Transcranial Magnetic Stimulation Sham

Study Details

Brief summary:

The goal of this clinical trial is to learn if using large-coil (or "deep") repetitive transcranial magnetic stimulation (rTMS) targeting the precuneus and surrounding areas is feasible, tolerable, and potentially efficacious for memory in Alzheimer's Disease. Previous work studying rTMS in Alzheimer's is mixed, but recent work studying rTMS of the precuneus is encouraging for both its short-term and long-term effects. The main questions this study aims to answer are:

Is deep rTMS of the precuneus feasible and tolerable in Alzheimer's?
Are there signs of positive brain changes in response to deep rTMS?
Is deep rTMS potentially efficacious for memory in Alzheimer's? Researchers will compare active stimulation to placebo stimulation while obtaining memory testing and measurements of the brain (imaging, scalp electrode measurements, bloodwork) to see if active treatment works to treat Mild Cognitive Impairment (MCI) and mild-to-moderate dementia due to Alzheimer's disease.

Participants will:

Engage with memory testing, brain scans, and bloodwork during a comprehensive assessment
Visit the clinic 3 times for 12 consolidated rTMS sessions, followed by 8 once weekly maintenance visits
Be offered a full open-label active treatment course after completing their treatment course if they are initially in the placebo group

Conditions

Alzheimer&Amp;Amp;#39;s Disease

Alzheimer Disease

Dementia Alzheimer Type

Mild Alzheimer&Amp;Amp;#39;s Disease

Moderate Alzheimer&Amp;Amp;#39;s Disease

Study ID

NCT06597942

Start date

Oct 17, 2024

Status verified date

Sep, 2026

Completion date

Dec, 2029

Anticipated

Primary completion date

Oct, 2029

Anticipated

Eligibility Criteria

Sex: All

Age: 55 - 70+

Healthy Volunteers: Not accepted

Inclusion Criteria:

Agreement to participate in study and able to complete informed consent process
Have a caregiver or study partner who can accompany them to all study visits
Have a known alternate surrogate decision-maker (in case needed) who can be present for informed consent
Established diagnosis of biomarker-positive (amyloid-PET, plasma or CSF amyloid ratio or phosphorylated tau) mild-moderate (clinical stages 3, 4, and 5) Alzheimer's Disease based on the 2024 Alzheimer's Association Framework
Age 55-100 at the start of the study.
Screening MOCA 12-25 (< 26, > 11)
Screening GDS score <6
Either 1) treated with memory-enhancing medication (cholinesterase inhibitor or other medications or treatments) for at least 2 months, 2) failed trial with no plan to re-trial, or 3) no trial planned during the course of the study for other reasons
No change in use of psychotropic medication (or other treatments) for the treatment of depression, anxiety, ADHD, or psychosis for 2 weeks prior to the study

Exclusion Criteria:

Unwilling or unable to provide informed consent as outlined below
Currently pregnant or potentially pregnant
Diagnosis of a dementia or cognitive disorder primarily or exclusively due to a cause other than Alzheimer's Disease
Diagnosis of severe Dementia (CDR > 2.0/ AA clinical stage 6) at the start of the study
History of substance use disorder currently not in sustained remission
Substance misuse within the past 6 months (excluding nicotine or caffeine)
History of stroke, traumatic brain injury with loss of consciousness, or other major neurologic disorder (e.g., epilepsy, Huntington's disease, Parkinson's disease)
History of seizure disorder or family history of seizure disorder in a first-degree relative
Poorly-controlled hypertension, cardiovascular disease, or cerebrovascular disease
History of any other major active medical, neurologic, or psychiatric illness affecting cognition (associated with cognitive impairment) or a participant's ability to safely and meaningfully participate in the study
Non-fluent in English (not native or functionally-native, specified here for cognitive testing purposes)
Contraindication to TMS or MRI including claustrophobia, MRI-incompatible or unknown metal in body (including facial tattoos with uknown or metallic inks), surgery within 60 days, certain implants (excluding dental fillings), or previous abnormal MRI results unrelated to a potential participant's dementia.
For the randomized stage only-has a history of prior TMS treatment (not TMS naïve)
Currently enrolled in an interventional memory-enhancement study
Alteration in cognitive-enhancement medication (or other treatment) dose within the past 2 months or active plans for dose alteration during the course of the study (previously unplanned changes that occur during the study will be examined on a case-by-case basis)
Has started treatment with lecanemab, donanemab, or any other monoclonal antibody for Alzheimer's Disease within the past 6 months OR has a history of treatment complicated by amyloid-related imaging abnormalities (ARIA)
Currently or within the past 2 weeks taking any of the following classes of medication:

Anticholinergic (e.g., tolterodine, benztropine)
Sedating antihistamines (e.g., diphenhydramine)
any drug that has significant anticholinergic or antihistaminic side effects (e.g., tricyclic antidepressant medications, mirtazapine).
Benzodiazepines. While not a strict rule out, this will be decided on a case-by-case basis
Opioid. While not a strict rule out, this will be decided on a case-by-case basis
Antiepileptic agents. While not a strict rule out, this will be decided on a case-by-case basis
Antipsychotic agents. While not a strict rule out, this will be decided on a case-by-case basis

Study Design

Enrollment

54 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Other

Interventions and Outcome Measures

Arms

experimental: Open-Label Active deep rTMS (First Study Stage)

The first stage of the study will consist of protocol refinement. In this first stage of 5-10 participants, all participants will receive open-label active treatment.

Treatment will consist of 16 sessions of deep rTMS spread over 5 weeks. The induction phase of treatment will be 4 sessions per day for 3 consecutive days (with 60 minutes between sessions), followed by 1 session per week for 4 weeks.

Individual sessions will consist of 1600 pulses of 20Hz rTMS delivered in 40 pulse trains to the precuneus (using MRI structural neuronavigation) at 100% of depth-corrected motor-threshold with a 28 second intertrain interval (roughly 20 minutes per session).

experimental: Randomized Active deep precuneus rTMS

The second stage of the study will consist of both active and sham treatment groups. Treatment will consist of 28 sessions of deep rTMS spread over 9 weeks. The induction phase of treatment will be 4 sessions per day for 3 consecutive days (with 30-60 minutes between sessions), followed by 1 visit per week (with two sessions per visit separated by 30-60 minutes) for 8 weeks. Individual sessions will consist of 1600 pulses of 20Hz rTMS delivered in 40 pulse trains to the precuneus (using MRI structural neuronavigation) at 100% of depth-corrected motor-threshold with a 20 second intertrain interval (roughly 15-20 minutes per session). The active group will receive this protocol using an active treatment coil delivering real rTMS.

sham comparator: Randomized Sham deep precuneus rTMS

The second stage of the study will consist of both active and sham treatment groups. Treatment will consist of 28 sessions of deep rTMS spread over 9 weeks. The induction phase of treatment will be 4 sessions per day for 3 consecutive days (with 30-60 minutes between sessions), followed by 1 visit per week (with two sessions per visit separated by 30-60 minutes) for 8 weeks. Individual sessions will consist of 1600 pulses of 20Hz rTMS delivered in 40 pulse trains to the precuneus (using MRI structural neuronavigation) at 100% of depth-corrected motor-threshold with a 20 second intertrain interval (roughly 15-20 minutes per session). The placebo group will receive this protocol using a sham TMS coil delivering inactive rTMS.

Participants in the sham/placebo group will be offered a full open-label extension treatment course of active rTMS on completion of the randomized phase.

Interventions

TMS

rTMS Stimulation Parameters Pulse count: 1600 pulses Frequency: 20Hz Pules per train: 40 pulses Inter-train interval: 20 seconds (28s originally) Intensity: 100% Motor Threshold (depth-corrected from MRI) Target: Precuneus using structural MRI navigation with MNI coordinates

Transcranial Magnetic Stimulation Sham

Sham coil placed in same location and set with same parameters as active treatment coil. However, this device will not output active treatment and scalp electrodes will mimic the sensation of rTMS for the participant.

Primary outcome measure

Completion Rate [ Time Frame: From enrollment to the end of treatment after 9 weeks ]

Central Contacts and Locations

Central contacts

Griffin Bohman

(310) 825-4781 TMSResearch@mednet.ucla.edu

Michael Leuchter, MD, MSc

(310) 206-0995 TMSResearch@mednet.ucla.edu

Locations

UCLA TMS Clinical and Research Service

Recruiting

Los Angeles, California, United States, 90095

Contacts

Cole Matthews, BA

(310) 825-7797 TMSResearch@mednet.ucla.edu

Doan Ngo, BS

(310) 825-7797 TMSResearch@mednet.ucla.edu

Principal Investigator:

Michael Leuchter, MD

More Information

Sponsor

University of California, Los Angeles

Last update posted

Sep 4, 2026

Last verified

Sep, 2026

Keywords

Clinical Trial
deep repetitive transcranial magnetic stimulation (deep rTMS)
precuneus
Mild-to-Moderate Probable Alzheimer&amp;#39;s Dementia

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by University of California, Los Angeles on 2026-09-04.