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

Primary Purpose

Alzheimer Disease, Mild Cognitive Impairment, Aging

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
repetitive transcranial magnetic stimulation (rTMS)
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alzheimer Disease

Eligibility Criteria

60 Years - 85 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Massachuetts General HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

Active stimulation

Sham stimulation

Arm Description

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).

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.

Outcomes

Primary Outcome Measures

Paired Associative Face Name Memory Test
A test of memory for face-name associations

Secondary Outcome Measures

Changes in intrinsic functional connectivity
Changes in region-to-region functional connectivity within the stimulated network will be assessed

Full Information

First Posted
March 2, 2020
Last Updated
March 11, 2020
Sponsor
Massachusetts General Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04294888
Brief Title
TMS in Preclinical and Prodromal AD: Modulation of Brain Networks and Memory
Official Title
TMS in Preclinical and Prodromal AD: Modulation of Brain Networks and Memory
Study Type
Interventional

2. Study Status

Record Verification Date
March 2020
Overall Recruitment Status
Recruiting
Study Start Date
March 2, 2020 (Actual)
Primary Completion Date
March 1, 2024 (Anticipated)
Study Completion Date
March 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer Disease, Mild Cognitive Impairment, Aging

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Model Description
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.
Masking
Participant
Masking Description
All participants will undergo SHAM stimulation as a control condition. They will be blinded as to whether they are receiving active or SHAM stimulation.
Allocation
Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Active stimulation
Arm Type
Experimental
Arm Description
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).
Arm Title
Sham stimulation
Arm Type
Sham Comparator
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
repetitive transcranial magnetic stimulation (rTMS)
Intervention Description
rTMS is a method to focally and reversibly stimulate a pre-specified cortical target. rTMS works through the principle of electromagnetic induction.
Primary Outcome Measure Information:
Title
Paired Associative Face Name Memory Test
Description
A test of memory for face-name associations
Time Frame
up to 5 weeks
Secondary Outcome Measure Information:
Title
Changes in intrinsic functional connectivity
Description
Changes in region-to-region functional connectivity within the stimulated network will be assessed
Time Frame
up to 5 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
60 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jessica A Collins, PhD
Phone
617-726-6217
Email
jcollins21@mgh.harvard.edu
Facility Information:
Facility Name
Massachuetts General Hospital
City
Charlestown
State/Province
Massachusetts
ZIP/Postal Code
02129
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Courtney Sullivan
Phone
617-643-5568
Email
csullivan65@partners.org

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
There is no plan to share IPD with researchers outside of this protocol.

Learn more about this trial

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

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