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

NCT ID: NCT04294888

Last Updated: 2020-03-12

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-03-02
• Study Completion Date: 2024-03-01

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

Alzheimer Disease; Mild Cognitive Impairment; Aging

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Active stimulation

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).

Group Type: EXPERIMENTAL

repetitive transcranial magnetic stimulation (rTMS)

Intervention Type: DEVICE

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

Sham stimulation

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.

Group Type: SHAM_COMPARATOR

repetitive transcranial magnetic stimulation (rTMS)

Intervention Type: DEVICE

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

Interventions

repetitive transcranial magnetic stimulation (rTMS)

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

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

1. Between the ages of 60-85

2. All participants will be native English speakers

3. Willing and able to consent to the protocol and undergo imaging and neuropsychological testing at the specified time points

4. Participants with aMCI will be asked to bring a study partner to all visits

5. Only patients with very mild or mild cognitive impairment (CDR 0.5 or CDR 1) will be included in the prodromal AD cohort

Exclusion Criteria

1. History of head trauma involving loss of consciousness or alteration in consciousness

2. Another major neurologic or psychiatric condition

3. Known presence of a structural brain lesion (e.g. tumor, cortical infarct)

4. 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

5. 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

6. Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the study protocol.

7. Unwilling to return for follow-up, undergo neuropsychological testing, TMS, and MR imaging

• Minimum Eligible Age: 60 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Jessica A. Collins, PhD

Instructor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Massachuetts General Hospital

Charlestown, Massachusetts, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Jessica A Collins, PhD

Role: CONTACT

jcollins21@mgh.harvard.edu

617-726-6217

Facility Contacts

Courtney Sullivan

Role: primary

csullivan65@partners.org

617-643-5568

Other Identifiers

2019P003445

Identifier Type: -

Identifier Source: org_study_id