Deep TMS for Comorbid Depression and Cognitive Impairment in Older Adults

October 11, 2023 updated by: Linda Mah, MD, Rotman Research Institute at Baycrest

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

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.

Study Overview

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.

Study Type

Interventional

Enrollment (Estimated)

28

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

    • Ontario
      • Toronto, Ontario, Canada, M6A 2E1
        • Recruiting
        • Rotman Research Institute at Baycrest
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

60 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Active H1 Coil deep rTMS active treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline on the Montgomery-Asberg Depression Rating Scale (MADRS)
Time Frame: 4 weeks
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.
4 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Remission Rates Compared Within Treatment Group
Time Frame: 4 weeks
Remission defined as MADRS < 10.
4 weeks
Response Rates Compared Within Treatment Group
Time Frame: 4 weeks
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.
4 weeks
Change From Baseline on the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q)
Time Frame: 4 weeks
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.
4 weeks
Change From Baseline on the Neuropsychological Battery
Time Frame: 4 weeks
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.
4 weeks
Change in Functional Connectivity between PFC and Limbic Regions
Time Frame: 4 weeks
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.
4 weeks
Change in Perfusion within Prefrontal Cortex (PFC) and Posterior Cingulate Cortex (PCC)
Time Frame: 4 weeks
Measured using Arterial Spin Labeling (ASL) fMRI scan.
4 weeks
Change in frontal theta power within the Anterior Cingulate Cortex (ACC)
Time Frame: 4 weeks
Measured with electroencephalography (EEG) and/or magnetoencephalography (MEG).
4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 23, 2018

Primary Completion (Estimated)

August 15, 2024

Study Completion (Estimated)

September 15, 2024

Study Registration Dates

First Submitted

September 7, 2018

First Submitted That Met QC Criteria

September 7, 2018

First Posted (Actual)

September 11, 2018

Study Record Updates

Last Update Posted (Actual)

October 13, 2023

Last Update Submitted That Met QC Criteria

October 11, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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