Deep TMS for Comorbid Depression and Cognitive Impairment in Older Adults

Major Depressive Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03665831
• Other study ID #: CICP-2-00095
• Status: Recruiting
• Phase: N/A
• Start date: October 23, 2018
• Est. completion date: September 15, 2024

Study information

• Verified date: October 2023
• Source: Rotman Research Institute at Baycrest
• Contact: Amanda Rahmadian, BSc
• Phone: 416-785-2500
• Email: dtms[@]research.baycrest.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 28
• Est. completion date: September 15, 2024
• Est. primary completion date: August 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Cognitive Dysfunction
• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder
• Mild Cognitive Impairment

Intervention

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.

Locations

Country	Name	City	State
Canada	Rotman Research Institute at Baycrest	Toronto	Ontario

Sponsors (3)

Lead Sponsor	Collaborator
Rotman Research Institute at Baycrest	Brainsway, Centre for Addiction and Mental Health

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	4 weeks
Secondary	Remission Rates Compared Within Treatment Group	Remission defined as MADRS < 10.	4 weeks
Secondary	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.	4 weeks
Secondary	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.	4 weeks
Secondary	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.	4 weeks
Secondary	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.	4 weeks
Secondary	Change in Perfusion within Prefrontal Cortex (PFC) and Posterior Cingulate Cortex (PCC)	Measured using Arterial Spin Labeling (ASL) fMRI scan.	4 weeks
Secondary	Change in frontal theta power within the Anterior Cingulate Cortex (ACC)	Measured with electroencephalography (EEG) and/or magnetoencephalography (MEG).	4 weeks