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dTMS for Subjective Cognitive Decline

Primary Purpose

Alzheimer Disease, Subjective Cognitive Decline

Status
Recruiting
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
Active Brainsway H7-Coil Deep TMS System
Sham Brainsway H7-Coil Deep TMS System
Cognitive Training
Sponsored by
Rotman Research Institute at Baycrest
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alzheimer Disease

Eligibility Criteria

55 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: have a family history of late onset sporadic Alzheimer's disease (AD) as defined by having a first degree relative, living or deceased, with a probable or confirmed diagnosis of AD have subjective memory decline and concern about memory changes score 26 or higher on the Montreal Cognitive Assessment (MoCA) are willing to provide informed consent are able to follow the treatment schedule are stable on medications for 2 months and are not expected to change medication during the entire study period (if they are taking medications) have a satisfactory safety screening questionnaire for TMS have an informant/study partner who is able to complete study questionnaires regarding the participant Exclusion Criteria: have a metal plate in their head, except in the mouth (such as an ear implant, implanted brain stimulators, aneurysm clips) have known increased pressure or a history of increased pressure in their brain, which may increase their risk for having seizures have a cardiac pacemaker have an implanted medication pump have a central venous line have a significant heart condition have current depression or a history of any psychotic disorder, bipolar disorder, eating disorder, obsessive compulsive disorder, post-traumatic stress disorder, or dementia other than AD have a history of substance abuse in the last 6 months have a history of stroke or other brain lesions have a personal history of epilepsy have a family history of epilepsy are a pregnant or breast-feeding woman have a history of abnormal MRI of the brain have significant hearing loss requiring use of hearing aids have untreated hypo- or hyper-thyroidism have TMS contraindications have unstable medical condition(s) regularly use benzodiazepines or other hypnotics within 2 weeks of randomization

Sites / Locations

  • Rotman Research Institute at BaycrestRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

20 sessions of dTMS and Cognitive Training

20 sessions of sham/control stimulation and Cognitive Training

Arm Description

Participants will receive dTMS followed by computerized cognitive training. dTMS: The motor threshold (MT) will be measured by delivering single stimulations to the motor cortex with gradually increased intensity. After defining the MT, the coil will be positioned anterior to the hot spot using the ruler on the participant's cap, and a dTMS session will be performed with the dosing of the stimulus intensity titrated slowly to approximately 120% of the motor threshold. On Day 1 of the treatment, stimulation will be delivered at an intensity ranging from 80% to 100% of the participant's MT depending on their initial tolerance to the stimulation. Stimulation intensity will then be slowly titrated by sequentially increasing the intensity by 10% over the remaining days of the first week until a maximum intensity of 120% of MT is achieved depending on the tolerability of the patient. Immediately following dTMS, participants will complete 20-30 minutes of cognitive training.

Participants will receive sham intervention followed by computerized cognitive training. The sham intervention consists of treatment with similar technical parameters which induce scalp sensations but do not penetrate into the brain. Immediately following dTMS, participants will complete 20-30 minutes of cognitive training.

Outcomes

Primary Outcome Measures

Percentage of scheduled treatment sessions that are attended by study participants
There are in total 20 sessions of dTMS intervention and 20 sessions of sham stimulation.

Secondary Outcome Measures

Change in baseline memory performance on a neuropsychological battery
Memory score from the neuropsychological battery at baseline will be compared to 4 weeks of intervention and at 1-month follow-up.
Change in executive function performance on a neuropsychological battery
Executive function scores from the neuropsychological battery at baseline will be compared to 4 weeks of intervention and at 1-month follow-up.
Change in baseline in scores on the Geriatric Depression Scale (GDS).
GDS is a 15-item self-report scale that measures an elderly individual's mood. A score greater than 5 suggests that the individual may be depressed. Administration time is approximately 5 minutes. The scores at baseline will be compared to 4 weeks of intervention and at 1-month follow-up.
Change in baseline in scores on the Geriatric Anxiety Inventory (GAI).
The GAI is a 20-item self-report measure of anxiety developed for older adults. Administration time is approximately 5 minutes. The scores at baseline will be compared to 4 weeks of intervention and at 1-month follow-up.
Change in baseline in scores on the Neuropsychiatric Inventory Questionnaire (NPI-Q)
The NPI assesses dementia-related behavioural symptoms including delusions, hallucinations, agitation/aggression, dysphoria, anxiety, euphoria, apathy, disinhibition, irritability/lability, aberrant motor activity, night-time behavioural disturbances and appetite and eating abnormalities. Administration time is approximately 15 minutes. The scores at baseline will be compared to 4 weeks of intervention and at 1-month follow-up.
Change in slow wave and resting state activity
Measured with electroencephalography (EEG) following 4 weeks of intervention and at 1-month follow-up.

Full Information

First Posted
October 11, 2023
Last Updated
October 20, 2023
Sponsor
Rotman Research Institute at Baycrest
Collaborators
Brainsway, Centre for Addiction and Mental Health
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1. Study Identification

Unique Protocol Identification Number
NCT06095063
Brief Title
dTMS for Subjective Cognitive Decline
Official Title
Effect of Deep Transcranial Magnetic Stimulation (dTMS) on Cognition in Older Adults With Subjective Cognitive Decline (SCD)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 15, 2023 (Anticipated)
Primary Completion Date
October 1, 2024 (Anticipated)
Study Completion Date
November 15, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Rotman Research Institute at Baycrest
Collaborators
Brainsway, Centre for Addiction and Mental Health

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
No

5. Study Description

Brief Summary
Deep transcranial magnetic stimulation (dTMS) is a brain stimulation technique that involves generating a brief magnetic field in a coil that is placed on the scalp. The magnetic field passes through the skull and induces a weak electrical current in the brain that briefly activates neural circuits at the stimulation site. The Brainsway dTMS H7-Coil is able to target an area of the brain that has been shown in studies to be linked to greater resilience to cognitive decline. In this study, the investigators will combine dTMS with cognitive training in older adults with subjective cognitive decline (SCD) and examine the effect of this treatment on memory, other cognitive abilities, and mood. In addition, the investigators will examine the combined effects of dTMS and cognitive training on brain activity as measured using electroencephalography (EEG). Approximately 30 older adults from ages 55 to 70 with SCD and a positive family history of Alzheimer's disease will be enrolled in this study.
Detailed Description
This study will examine the effects of combining cognitive remediation with neurostimulation using deep transcranial magnetic stimulation (dTMS) and the H7-coil to target the anterior cingulate cortex (ACC) in older adults at risk for developing Alzheimer's disease (AD). Thirty older adults with subjective cognitive decline (SCD) and a family history of AD will participate in a single-site randomized double-blind sham-controlled cross-over trial of dTMS of the ACC in conjunction with active cognitive remediation for both sham and dTMS interventions. The primary goal of the study is to establish the feasibility of dTMS and cognitive training as a means to improve cognitive abilities in SCD. Secondary goals are to obtain preliminary evidence of improvement in executive function and memory abilities following dTMS and cognitive training. This trial is a first step towards developing effective neurostimulation protocols to reduce cognitive decline in older adults at risk for developing AD.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer Disease, Subjective Cognitive Decline

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
20 sessions of dTMS and Cognitive Training
Arm Type
Experimental
Arm Description
Participants will receive dTMS followed by computerized cognitive training. dTMS: The motor threshold (MT) will be measured by delivering single stimulations to the motor cortex with gradually increased intensity. After defining the MT, the coil will be positioned anterior to the hot spot using the ruler on the participant's cap, and a dTMS session will be performed with the dosing of the stimulus intensity titrated slowly to approximately 120% of the motor threshold. On Day 1 of the treatment, stimulation will be delivered at an intensity ranging from 80% to 100% of the participant's MT depending on their initial tolerance to the stimulation. Stimulation intensity will then be slowly titrated by sequentially increasing the intensity by 10% over the remaining days of the first week until a maximum intensity of 120% of MT is achieved depending on the tolerability of the patient. Immediately following dTMS, participants will complete 20-30 minutes of cognitive training.
Arm Title
20 sessions of sham/control stimulation and Cognitive Training
Arm Type
Sham Comparator
Arm Description
Participants will receive sham intervention followed by computerized cognitive training. The sham intervention consists of treatment with similar technical parameters which induce scalp sensations but do not penetrate into the brain. Immediately following dTMS, participants will complete 20-30 minutes of cognitive training.
Intervention Type
Device
Intervention Name(s)
Active Brainsway H7-Coil Deep TMS System
Intervention Description
Deep Transcranial Magnetic Stimulation (dTMS) is a new form of TMS which allows direct stimulation of deeper neuronal pathways than the standard TMS. The H-coil is a novel dTMS coil designed to allow deeper brain stimulation without a significant increase of electric fields induced in superficial cortical regions. dTMS will be administered daily for 4 consecutive weeks.
Intervention Type
Device
Intervention Name(s)
Sham Brainsway H7-Coil Deep TMS System
Intervention Description
In addition to the active H-coil, a sham coil is included in the system. The active and sham coils are connected to a control switch, which alternates between real and sham operation modes. The sham treatment will be administered daily for 4 consecutive weeks.
Intervention Type
Other
Intervention Name(s)
Cognitive Training
Intervention Description
Cognitive training will be conducted using the BrainHQ software program.
Primary Outcome Measure Information:
Title
Percentage of scheduled treatment sessions that are attended by study participants
Description
There are in total 20 sessions of dTMS intervention and 20 sessions of sham stimulation.
Time Frame
19 weeks
Secondary Outcome Measure Information:
Title
Change in baseline memory performance on a neuropsychological battery
Description
Memory score from the neuropsychological battery at baseline will be compared to 4 weeks of intervention and at 1-month follow-up.
Time Frame
19 weeks
Title
Change in executive function performance on a neuropsychological battery
Description
Executive function scores from the neuropsychological battery at baseline will be compared to 4 weeks of intervention and at 1-month follow-up.
Time Frame
19 weeks
Title
Change in baseline in scores on the Geriatric Depression Scale (GDS).
Description
GDS is a 15-item self-report scale that measures an elderly individual's mood. A score greater than 5 suggests that the individual may be depressed. Administration time is approximately 5 minutes. The scores at baseline will be compared to 4 weeks of intervention and at 1-month follow-up.
Time Frame
19 weeks
Title
Change in baseline in scores on the Geriatric Anxiety Inventory (GAI).
Description
The GAI is a 20-item self-report measure of anxiety developed for older adults. Administration time is approximately 5 minutes. The scores at baseline will be compared to 4 weeks of intervention and at 1-month follow-up.
Time Frame
19 weeks
Title
Change in baseline in scores on the Neuropsychiatric Inventory Questionnaire (NPI-Q)
Description
The NPI assesses dementia-related behavioural symptoms including delusions, hallucinations, agitation/aggression, dysphoria, anxiety, euphoria, apathy, disinhibition, irritability/lability, aberrant motor activity, night-time behavioural disturbances and appetite and eating abnormalities. Administration time is approximately 15 minutes. The scores at baseline will be compared to 4 weeks of intervention and at 1-month follow-up.
Time Frame
19 weeks
Title
Change in slow wave and resting state activity
Description
Measured with electroencephalography (EEG) following 4 weeks of intervention and at 1-month follow-up.
Time Frame
17 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
55 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: have a family history of late onset sporadic Alzheimer's disease (AD) as defined by having a first degree relative, living or deceased, with a probable or confirmed diagnosis of AD have subjective memory decline and concern about memory changes score 26 or higher on the Montreal Cognitive Assessment (MoCA) are willing to provide informed consent are able to follow the treatment schedule are stable on medications for 2 months and are not expected to change medication during the entire study period (if they are taking medications) have a satisfactory safety screening questionnaire for TMS have an informant/study partner who is able to complete study questionnaires regarding the participant Exclusion Criteria: have a metal plate in their head, except in the mouth (such as an ear implant, implanted brain stimulators, aneurysm clips) have known increased pressure or a history of increased pressure in their brain, which may increase their risk for having seizures have a cardiac pacemaker have an implanted medication pump have a central venous line have a significant heart condition have current depression or a history of any psychotic disorder, bipolar disorder, eating disorder, obsessive compulsive disorder, post-traumatic stress disorder, or dementia other than AD have a history of substance abuse in the last 6 months have a history of stroke or other brain lesions have a personal history of epilepsy have a family history of epilepsy are a pregnant or breast-feeding woman have a history of abnormal MRI of the brain have significant hearing loss requiring use of hearing aids have untreated hypo- or hyper-thyroidism have TMS contraindications have unstable medical condition(s) regularly use benzodiazepines or other hypnotics within 2 weeks of randomization
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Amanda Rahmadian
Phone
416-785-2500
Ext
3434
Email
dtms@research.baycrest.org
First Name & Middle Initial & Last Name or Official Title & Degree
Linda Mah
Phone
416-785-2500
Ext
3365
Email
lmah@research.baycrest.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Linda Mah
Organizational Affiliation
Baycrest Rotman Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Rotman Research Institute at Baycrest
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M6A 2E1
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Linda Mah, MD
Phone
416-785-2500
Ext
3365
Email
lmah@research.baycrest.org

12. IPD Sharing Statement

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dTMS for Subjective Cognitive Decline

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