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Deep TMS for Comorbid Depression and Cognitive Impairment in Older Adults

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03665831
Recruitment Status : Recruiting
First Posted : September 11, 2018
Last Update Posted : October 1, 2019
Centre for Addiction and Mental Health
Information provided by (Responsible Party):
Linda Mah, MD, Rotman Research Institute at Baycrest

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.

Condition or disease Intervention/treatment Phase
Major Depressive Disorder Alzheimer Disease Mild Cognitive Impairment Device: Brainsway H1-Coil Deep TMS System Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 28 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Treatment of Comorbid Depression and Cognitive Impairment in Older Adults With Neurocognitive Disorders Using Deep Transcranial Magnetic Stimulation (dTMS)
Actual Study Start Date : October 23, 2018
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : April 2020

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Active H1 Coil deep rTMS active treatment Device: Brainsway H1-Coil Deep TMS System
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 Measures :
  1. 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.

Secondary Outcome Measures :
  1. Remission Rates Compared Within Treatment Group [ Time Frame: 4 weeks ]
    Remission defined as MADRS < 10.

  2. 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.

  3. 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. 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.

  5. 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.

  6. Change in Perfusion within Prefrontal Cortex (PFC) and Posterior Cingulate Cortex (PCC) [ Time Frame: 4 weeks ]
    Measured using Arterial Spin Labeling (ASL) fMRI scan.

  7. Change in frontal theta power within the Anterior Cingulate Cortex (ACC) [ Time Frame: 4 weeks ]
    Measured with electroencephalography (EEG) and/or magnetoencephalography (MEG).

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   60 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03665831

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Contact: Christina Deonarain, MSc 416-785-2500 ext 3434
Contact: Linda Mah, MD 416-785-2500 ext 3365

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Canada, Ontario
Rotman Research Institute at Baycrest Recruiting
Toronto, Ontario, Canada, M6A 2E1
Contact: Linda Mah, MD, MHS, FRCPC    416-785-2500 ext 3365   
Sponsors and Collaborators
Rotman Research Institute at Baycrest
Centre for Addiction and Mental Health
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Responsible Party: Linda Mah, MD, Clinician Scientist, Rotman Research Institute at Baycrest Identifier: NCT03665831    
Other Study ID Numbers: CICP-2-00095
First Posted: September 11, 2018    Key Record Dates
Last Update Posted: October 1, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Keywords provided by Linda Mah, MD, Rotman Research Institute at Baycrest:
Additional relevant MeSH terms:
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Alzheimer Disease
Depressive Disorder
Depressive Disorder, Major
Cognitive Dysfunction
Behavioral Symptoms
Mood Disorders
Mental Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neurocognitive Disorders
Cognition Disorders