Transcranial Magnetic Stimulation Treatment for Alzheimer's Disease

NCT06538311 | Recruiting Early Phase 1 DMC FDA Device

• 1 other identifier: 2022A002983
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

In this research study we want to learn more about the effects of non-invasive brain stimulation on memory and brain-network function in cognitively unimpaired older adults and in patients with amnestic mild cognitive impairment (aMCI). 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 memory. Changes resulting from this stimulation will be measured with behavioral tests of memory and general cognition, as well as by taking images of your brain 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

Mild Cognitive Impairment; Amnestic Symptoms; Alzheimer Disease; Logopenic Progressive Aphasia

Keywords

Transcranial Magnetic Stimulation

Outcome Measures

Primary Outcomes (2)

• Changes in Memory

  This will include observed changes in memory as a result of the stimulation through neuropsychological testing.

  Baseline and post-treatment Day 11

• Changes in Brain Network Connectivity

  This will include observed changes in resting-state functional connectivity as a result of the stimulation.

  Baseline and post-treatment Day 11

Study Arms (1)

AD, aMCI, lvPPA patients, and preclinical AD

EXPERIMENTAL

All participants will receive the same study interventions in a within-subject crossover design.

Device: Active rTMS; Device: Sham rTMS

Interventions

Active rTMS DEVICE

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).

AD, aMCI, lvPPA patients, and preclinical AD

Sham rTMS DEVICE

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).

AD, aMCI, lvPPA patients, and preclinical AD

Eligibility Criteria

• Age: 40 Years - 99 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Patients with PPA will be asked to bring a study partner to all visits
• Patients with very mild or mild PPA, patients with amnestic mild cognitive impairment and cognitively unimpaired participants with preclinical AD will be included.

You may not qualify if:

• 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.
• 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.
• Subjects actively on anti-amyloid treatments. This is because they are at risk for bleeding due to amyloid-related imaging abnormalities (ARIA) that could provoke seizures.

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02129, United States

RECRUITING

Related Publications (2)

• Wang JX, Rogers LM, Gross EZ, Ryals AJ, Dokucu ME, Brandstatt KL, Hermiller MS, Voss JL. Targeted enhancement of cortical-hippocampal brain networks and associative memory. Science. 2014 Aug 29;345(6200):1054-7. doi: 10.1126/science.1252900.

  PMID: 25170153 BACKGROUND

• Damoiseaux JS, Prater KE, Miller BL, Greicius MD. Functional connectivity tracks clinical deterioration in Alzheimer's disease. Neurobiol Aging. 2012 Apr;33(4):828.e19-30. doi: 10.1016/j.neurobiolaging.2011.06.024. Epub 2011 Aug 16.

  PMID: 21840627 BACKGROUND

MeSH Terms

Conditions

Alzheimer Disease; Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders

Central Study Contacts

Alexandra Touroutoglou, PhD

CONTACT

6176436348; atouroutoglou@mgh.harvard.edu

Jordan Walter, BA

CONTACT

6177266207; jwalter2@mgh.harvard.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Through use of SHAM rTMS stimulation
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Neurology

Model Details: Within-subject crossover design

Study Record Dates

• First Submitted: August 1, 2024
• First Posted: August 5, 2024
• Study Start: May 1, 2023
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): March 31, 2027
• Last Updated: May 6, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)