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Deep TMS for Comorbid Depression and Cognitive Impairment in Older Adults

Primary Purpose

Major Depressive Disorder, Alzheimer Disease, Mild Cognitive Impairment

Status

Recruiting

Phase

Not Applicable

Locations

Canada

Study Type

Interventional

Intervention

Brainsway H1-Coil Deep TMS System

About this trial

This is an interventional treatment trial for Major Depressive Disorder focused on measuring dTMS, depression, magnetic, iTBS

Eligibility Criteria

60 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

meet DSM 5 criteria for Major or Mild Neurocognitive Disorder due to Alzheimer's disease with Clinical Dementia Rating Scale (CDR) score of at least 0.5
have been diagnosed with DSM5 Major Depressive Disorder, with the current episode longer than 4 weeks but less than 5 years
did not respond to or did not tolerate antidepressant treatment
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 disease or history of stroke
Modified Hachinski Score (MHIS) > 3 (to exclude those with significant vascular component to memory loss)
have 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
are taking psychotropic medications including antidepressant medications, antipsychotics or mood stabilizing medications due to increased risk of seizure
are taking memantine
have a history of abnormal MRI of the brain
have significant hearing loss requiring use of hearing aids
have untreated hypo- or hyper-thyroidism

Sites / Locations

Rotman Research Institute at BaycrestRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Active H1 Coil deep rTMS active treatment

Arm Description

Outcomes

Primary Outcome Measures

Change From Baseline on the Montgomery-Asberg Depression Rating Scale (MADRS)

Therapeutic efficacy will be evaluated with the MADRS, a 10-item checklist. An effect size (Cohen's d) of 0.5 will be considered a minimally important effect size.

Secondary Outcome Measures

Remission Rates Compared Within Treatment Group

Remission defined as MADRS < 10.

Response Rates Compared Within Treatment Group

Response rate refers to the percentage of patients who responded to dTMS treatment and response is defined as a ≥50% reduction in MADRS score from baseline.

Change From Baseline on the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q)

This 16-item questionnaire is designed to help assess the degree of enjoyment and satisfaction experienced during the past week. Administration time is approximately 5 minutes.

Change From Baseline on the Neuropsychological Battery

Cognitive scores from the neuropsychological battery at baseline will be compared to 4 weeks post-intervention Cognitive domains tested include executive function, memory, language, attention, and intelligence.

Change in Functional Connectivity between PFC and Limbic Regions

Subjects will have magnetic resonance imaging (MRI) scans of the brain. The change in functional connectivity between PFC and limbic regions, and within the default mode network, at rest is measured using resting state fMRI.

Change in Perfusion within Prefrontal Cortex (PFC) and Posterior Cingulate Cortex (PCC)

Measured using Arterial Spin Labeling (ASL) fMRI scan.

Change in frontal theta power within the Anterior Cingulate Cortex (ACC)

Measured with electroencephalography (EEG) and/or magnetoencephalography (MEG).

Full Information

NCT ID

NCT03665831

First Posted

September 7, 2018

Last Updated

October 11, 2023

Sponsor

Rotman Research Institute at Baycrest

Collaborators

Brainsway, Centre for Addiction and Mental Health

1. Study Identification

Unique Protocol Identification Number

NCT03665831

Brief Title

Deep TMS for Comorbid Depression and Cognitive Impairment in Older Adults

Official Title

Treatment of Comorbid Depression and Cognitive Impairment in Older Adults With Neurocognitive Disorders Using Deep Transcranial Magnetic Stimulation (dTMS)

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Recruiting

Study Start Date

October 23, 2018 (Actual)

Primary Completion Date

August 15, 2024 (Anticipated)

Study Completion Date

September 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

Studies a U.S. FDA-regulated Device Product

Yes

Data Monitoring Committee

5. Study Description

Brief Summary

In this study, the investigators will be examining the effects of the deep repetitive transcranial magnetic stimulation (rTMS) using the H1 coil in patients over the age of 60 diagnosed with mild to early-moderate Alzheimer's disease (AD) or mild cognitive impairment (MCI) and comorbid Major Depressive Disorder (MDD) who have been unable to tolerate or failed to respond to antidepressant medications. The coil was designed to stimulate deeper regions of the left dorsolateral prefrontal cortex (DLPFC). Based on prior research, the investigators propose that active stimulation with the H1 coil for 4 weeks may result in significant remission rates and will be tolerable and safe.

Detailed Description

This study is an open-label trial to evaluate the safety and efficacy of H1-coil dTMS in treating depression in MCI and mild AD patients over 60 years of age who have not tolerated or failed to respond to antidepressant medications. 28 patients will be assigned to receive 4 consecutive weeks of daily active dTMS treatment. The long-term effects of treatment on emotional cognitive measures will be assessed at a 4-week follow-up visit (8 weeks from baseline). Symptom change and remission criteria will be assessed using the Montogmery-Asberg Depression Rating Scale (MADRS). Cognition will be assessed using a validated neuropsychological battery. We will also offer patients to receive 4 weeks of treatment using theta-burst TMS, which is a milder version of TMS.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Major Depressive Disorder, Alzheimer Disease, Mild Cognitive Impairment

Keywords

dTMS, depression, magnetic, iTBS

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

28 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Active H1 Coil deep rTMS active treatment

Arm Type

Experimental

Intervention Type

Device

Intervention Name(s)

Brainsway H1-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.

Primary Outcome Measure Information:

Title

Change From Baseline on the Montgomery-Asberg Depression Rating Scale (MADRS)

Description

Therapeutic efficacy will be evaluated with the MADRS, a 10-item checklist. An effect size (Cohen's d) of 0.5 will be considered a minimally important effect size.

Time Frame

4 weeks

Secondary Outcome Measure Information:

Title

Remission Rates Compared Within Treatment Group

Description

Remission defined as MADRS < 10.

Time Frame

4 weeks

Title

Response Rates Compared Within Treatment Group

Description

Response rate refers to the percentage of patients who responded to dTMS treatment and response is defined as a ≥50% reduction in MADRS score from baseline.

Time Frame

4 weeks

Title

Change From Baseline on the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q)

Description

This 16-item questionnaire is designed to help assess the degree of enjoyment and satisfaction experienced during the past week. Administration time is approximately 5 minutes.

Time Frame

4 weeks

Title

Change From Baseline on the Neuropsychological Battery

Description

Time Frame

4 weeks

Title

Change in Functional Connectivity between PFC and Limbic Regions

Description

Time Frame

4 weeks

Title

Change in Perfusion within Prefrontal Cortex (PFC) and Posterior Cingulate Cortex (PCC)

Description

Measured using Arterial Spin Labeling (ASL) fMRI scan.

Time Frame

4 weeks

Title

Change in frontal theta power within the Anterior Cingulate Cortex (ACC)

Description

Measured with electroencephalography (EEG) and/or magnetoencephalography (MEG).

Time Frame

4 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: meet DSM 5 criteria for Major or Mild Neurocognitive Disorder due to Alzheimer's disease with Clinical Dementia Rating Scale (CDR) score of at least 0.5 have been diagnosed with DSM5 Major Depressive Disorder, with the current episode longer than 4 weeks but less than 5 years did not respond to or did not tolerate antidepressant treatment 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 disease or history of stroke Modified Hachinski Score (MHIS) > 3 (to exclude those with significant vascular component to memory loss) have 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 are taking psychotropic medications including antidepressant medications, antipsychotics or mood stabilizing medications due to increased risk of seizure are taking memantine have a history of abnormal MRI of the brain have significant hearing loss requiring use of hearing aids have untreated hypo- or hyper-thyroidism

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Amanda Rahmadian, BSc

Phone

416-785-2500

Ext

3434

dtms@research.baycrest.org

First Name & Middle Initial & Last Name or Official Title & Degree

Linda Mah, MD

Phone

416-785-2500

Ext

3365

lmah@research.baycrest.org

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, MHS, FRCPC

Phone

416-785-2500

Ext

3365

lmah@research.baycrest.org

12. IPD Sharing Statement

Citations:

PubMed Identifier

33153503

Citation

Hodzic-Santor BH, Meltzer JA, Verhoeff NPLG, Blumberger DM, Mah L. Safety, tolerability, and feasibility of deep transcranial magnetic stimulation for late-life depression with comorbid major or mild neurocognitive disorder. Int Psychogeriatr. 2021 Jan;33(1):99-101. doi: 10.1017/S1041610220003543. Epub 2020 Nov 6. No abstract available.

Results Reference

derived

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Deep TMS for Comorbid Depression and Cognitive Impairment in Older Adults

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