TMS in Preclinical and Prodromal AD: Modulation of Brain Networks and Memory

NCT04294888 | Terminated FDA Device

• 1 other identifier: 2019P003445
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the effects of non-invasive brain stimulation on memory in cognitively unimpaired older adults and in patients amnestic mild cognitive impairment (aMCI) due to Alzheimer's disease (AD). This study will use repetitive Transcranial Magnetic Stimulation (rTMS) to stimulate nodes of the Default Mode Network (DMN)- which is thought to support episodic memory and to be affected by Alzheimer's pathology. We will use functional connectivity MRI (fcMRI) to assess changes in functional network architecture following the stimulation. We will also assess putative cognitive improvements resulting from the stimulation by in-depth memory testing.

Conditions

Mild Cognitive Impairment; Aging; Alzheimer Disease

Outcome Measures

Primary Outcomes (1)

• Paired Associative Face Name Memory Test

  A test of memory for face-name associations

  up to 5 weeks

Secondary Outcomes (1)

• Changes in intrinsic functional connectivity

  up to 5 weeks

Study Arms (2)

Active stimulation

EXPERIMENTAL

Active rTMS will be administered with a MagPro X100 stimulator (MagVenture, Denmark), using a 70 mm figure-of-eight liquid cooled coil capable of doing active or sham stimulation (e.g. the Cool B70 coil or the Cool B65 A/P coil). Active rTMS will be delivered at 80% of a patient's active motor threshold. rTMS will be administered in an excitatory iTBS pattern. Stimulation parameters will remain well within established safety guidelines (Rossi et al. 2009).

Device: repetitive transcranial magnetic stimulation (rTMS)

Sham stimulation

SHAM COMPARATOR

SHAM stimulation will also be administered with a MagPro X100 stimulator (MagVenture, Denmark), using a 70 mm figure-of-eight liquid cooled coil capable of doing active or sham stimulation (e.g. the Cool B70 coil or the Cool B65 A/P coil). SHAM rTMS will be delivered at 80% of a patient's active motor threshold. SHAM stimulation will be delivered to the exact same cortical targets as active rTMS. While no electromagnetic stimulation will be delivered during SHAM, the sounds will approximate active stimulation and skin electrodes will approximate the sensation of active rTMS. Inclusion of a sham condition in this protocol is critical to measure whether or not the stimulation is improving memory performance, or whether practice effects or other non-specific effects are responsible for any changes in memory which may be observed.

Device: repetitive transcranial magnetic stimulation (rTMS)

Interventions

repetitive transcranial magnetic stimulation (rTMS) DEVICE

rTMS is a method to focally and reversibly stimulate a pre-specified cortical target. rTMS works through the principle of electromagnetic induction.

Active stimulation; Sham stimulation

Eligibility Criteria

• Age: 60 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Between the ages of 60-85
• All participants will be native English speakers
• Willing and able to consent to the protocol and undergo imaging and neuropsychological testing at the specified time points
• Participants with aMCI will be asked to bring a study partner to all visits
• Only patients with very mild or mild cognitive impairment (CDR 0.5 or CDR 1) will be included in the prodromal AD cohort

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

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachuetts General Hospital

Charlestown, Massachusetts, 02129, United States

Location

MeSH Terms

Conditions

Alzheimer Disease; Cognitive Dysfunction

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: All participants will undergo SHAM stimulation as a control condition. They will be blinded as to whether they are receiving active or SHAM stimulation.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Neurologist

Model Details: Participants will each undergo, in a crossover, within-subject design, two blocks of rTMS: active and SHAM.The order of active and SHAM blocks will be counterbalanced across subjects.

Study Record Dates

• First Submitted: March 2, 2020
• First Posted: March 4, 2020
• Study Start: March 2, 2020
• Primary Completion: June 23, 2021
• Study Completion: June 23, 2021
• Last Updated: March 20, 2026

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)