Back to results

Deep rTMS for Depression in Older Adults: A Pilot Study (DIVINE)

Primary Purpose

Major Depressive Disorder

Status

Recruiting

Phase

Not Applicable

Locations

Canada

Study Type

Interventional

Intervention

Brainsway H4-Coil Deep TMS System

Brainsway H7-Coil Deep TMS System

About this trial

This is an interventional health services research trial for Major Depressive Disorder focused on measuring Major Depressive Disorder, MDD, depressive disorder, depression, late-life depression, mood disorders, deep transcranial magnetic stimulation, deep TMS, dTMS, H coil, H-coil, older adults, H4-coil, H7-coil

Eligibility Criteria

60 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: A) 60 - 85 years old B) Able to provide informed consent to participate in the study C) MDD diagnosis, single or recurrent episode, assessed using Evaluation of the Diagnostic Assessment Research Tool (DART) Screener for DSM-5 Mood Disorder Module D) Total score of at least 20 on the 24-item Hamilton Depression Rating Scale (HDRS-24) at screening visit E) Treatment resistance to antidepressant pharmacotherapy during the current episode as indexed by Antidepressant Treatment History Form - Short Form (ATHF - SF). Specifically, participants will be required to have failed at least one or to have had an inadequate trial (including intolerance) to at least two antidepressants in the current episode F) Participants will be required to be on stable dosages of other psychotropic medications for at least 4 weeks prior to screening Exclusion Criteria: A) Primary diagnosis of bipolar I or II disorder; psychotic disorder; obsessive-compulsive, post-traumatic stress, anxiety, or personality disorder; participants with anxiety or personality disorders will be eligible if is not their primary diagnosis B) Active suicidal behavior C) Substance dependence/abuse in the past 3 months before entering the study (this will be screened via self-report and verified by urine screening test) D) Possible dementia diagnosis based on a Mini Mental Status Exam (MMSE) score of <24 and clinical presentation of dementia E) Unsuccessful ECT treatment on the current episode F) Traditional contraindications to rTMS: Intracranial or metal implants in the head or nearby regions, excluding the mouth, that cannot be safely removed; History of epilepsy or seizures; Active unstable medical condition (recent laboratory and neuroimaging alterations); Pacemaker and/or implantable cardioverter-defibrillators; current use of bupropion >300 mg/day as it is associated with risk of seizures, treatment with equivalent benzodiazepine dose to lorazepam >2 mg/day G) People with severe literacy, visual, or hearing issues that affect their ability to engage in the interviews

Sites / Locations

Peter Boris Centre for Addictions Research, St. Joseph's Healthcare HamiltonRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Active H4-coil dTMS treatment

Active H7-coil dTMS treatment

Arm Description

Outcomes

Primary Outcome Measures

Feasibility criteria 1: Protocol completion

Percentage of intervention sessions completed

Feasibility criteria 2: Retention rate

Percentage of participants who complete study once enrolled

Feasibility criteria 3: Screening rates and capacity

Number of participants (n) screened; n enrolled as a percentage of n screened monthly

Feasibility criteria 4: Recruitment rate and capacity

Total number of participants recruited and enrolled per month.

Feasibility criteria 5: Duration of intervention and assessment processes

Compared to estimated times, the actual mean times (in min) from start to finish for each dTMS intervention session and mean time (in hours) from start to finish for each visit.

Feasibility criteria 5: Safety of H-coil dTMS treatment

Total number of adverse events reported during the treatment sessions assessed by the Side Effects Questionnaire for dTMS (custom-developed for study). At each dTMS stimulation session, participants will complete a questionnaire to evaluate potential adverse effects of dTMS (headache, neck pain, itching and redness at the site of stimulation) according to a 4-point scale.

Tolerability of H-coil dTMS treatment

Percentage of participants withdrawn or terminated following enrollment due to adverse events

Secondary Outcome Measures

Change from baseline on the Hamilton Depression Rating Scale- 24 item (HDRS-24).

The HDRS-24 will be used as the primary measure of depression. Symptoms of depression will be assessed with the HDRS-24 (a 24-item depression checklist) at multiple visits: the in-person screen (V0), baseline (V1), end-of-week dTMS sessions (V5, V10, V15, V20), and the 2-week follow-up.

Changes from baseline on the Geriatric Depression 30-item Scale (GDS-30)

The GDS-30 will be used as a second measure of depression, a 30-item checklist, at the baseline (V1), midpoint (V10) and endpoint (V20) visits and at the 2-week follow-up.

Change from baseline on the General Anxiety Disorder- 7 item (GAD-7)

Symptoms of anxiety will be assessed using this 7-item questionnaire at the baseline (V1), midpoint (V10) and endpoint (V20) visits and at the 2-week follow-up.

Change from baseline on the Pittsburgh Sleeping Quality Index (PSQI)

Sleep will be monitored and assessed using the PSQI at the baseline (V1), midpoint (V10) and endpoint (V20) visits and at the 2-week follow-up.

Change from baseline on the Patient Health Questionnaire (PHQ - Somatic Symptoms)

Somatic symptoms will be evaluated using the PHQ somatic inventory at the baseline (V1), midpoint (V10) and endpoint (V20) visits and at the 2-week follow-up

Changes from baseline in resting-state EEG

Using electroencephalography (EEG), we will assess alpha, theta and gamma rhythms in fronto-temporo-parietal region, including assessment of connectivity and coherence. We will additionally measure cross-frequency coupling named theta (4-8Hz)-gamma (>25Hz) phase-amplitude coupling (PAC). We will also investigate phase synchronization in upper theta frequency band between prefrontal and temporal areas. Changes in these EEG parameters will be correlated with changes in mood severity and cognitive status, with a focus on working memory improvements. EEG will be performed before dTMS sessions at baseline (V1) and at the end of each week (V5, V10, V15 and V20) by using a wireless dry electrode portable EEG system (CGX Quick 20r). Resting state connectivity, coherence, PAC, and synchronization assessed by EEG will use standardized data processing pipelines in EEG Lab.

Changes from baseline in neurocognitive functioning (Repeatable Battery of Neuropsychological Status [RBANS])

Neurocognitive performance will be assessed with the Repeatable Battery of Neuropsychological Status. Assessments will be completed at baseline (V1) and at post-treatment (V20).

Full Information

NCT ID

NCT05855850

First Posted

February 6, 2023

Last Updated

May 9, 2023

Sponsor

St. Joseph's Healthcare Hamilton

Collaborators

Peter Boris Centre for Addictions Research (PBCAR)

1. Study Identification

Unique Protocol Identification Number

NCT05855850

Brief Title

Deep rTMS for Depression in Older Adults: A Pilot Study

Acronym

DIVINE

Official Title

DIfferential Feasibility and Tolerability of Deep repetitiVe transcranIal MagNEtic Stimulation for Depression in Older Adults (DIVINE Trial): A Pilot Study

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Recruiting

Study Start Date

April 18, 2023 (Actual)

Primary Completion Date

August 31, 2023 (Anticipated)

Study Completion Date

December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

St. Joseph's Healthcare Hamilton

Collaborators

Peter Boris Centre for Addictions Research (PBCAR)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

Brief Summary

This study aims to: (1) assess the feasibility and tolerability of two active dTMS coils - H4 and H7 - in older adults with depression; and (2) clinical response measured by change from baseline on the Hamilton Depression Rating Scale- 24 item; changes in cognitive function through neuropsychological assessment; and changes in regional electrophysiological activity and functional connectivity indexed by EEG. Through a parallel design, participants will complete a four-week course of five dTMS sessions per week, for a total of 20 stimulation sessions. Participants will be randomly assigned to either coil (H4 or H7) and will complete questionnaires examining side effects, mental health symptoms, and cognition. Participant EEG data will be measured and collected at baseline and at the end of each week. Collectively, the study will address the absolute and differential feasibility and tolerability of the two active coils to provide preliminary data for a future randomized controlled trial comparing one or both of these novel interventions to the established H1-coil and a sham stimulation (placebo) control.

Detailed Description

Transcranial magnetic stimulation (TMS) is a non-invasive therapeutic technique used to stimulate regions of the brain using magnetic pulses. Repeated TMS delivers sequences of pulses for multiple days in a row and is an approved treatment for several psychiatric conditions. Deep TMS (dTMS) is a new technique that uses modified magnetic Hesed coils (H-coils) to stimulate deeper regions of the brain and has been FDA- and Health Canada-approved for major depressive disorder (MDD), obsessive-compulsive disorder, smoking cessation, and anxious-depression in adults. For older adults (60+), traditional rTMS has also shown efficacy for MDD (60+) and one RCT has found benefit for the H1 dTMS coil, but no trials have examined the H4 and H7 coils in this population. This innovative pilot study will explore dTMS feasibility and tolerability (i.e., side effects, impacts on mental health and cognition) of these two dTMS coils (H4, targeting insula and H7, targeting anterior cingulate cortex) in older adults with depression. The pilot will provide critical preliminary data for a future trial comparing these novel interventions to the H1-coil and a sham stimulation control. There is sparse literature examining the effects of dTMS on cognition, as measured by neuropsychological testing, and brain activity, as measured by electroencephalogram (EEG), while comparing different dTMS H-coils. Therefore, a second feature of the design includes assessing both domains over the course of treatment. The results will lay the foundation for a future randomized controlled trial examining the efficacy and mechanisms of one or both of these novel forms of neurostimulation for MDD in older adults.

6. Conditions and Keywords

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

Major Depressive Disorder

Keywords

Major Depressive Disorder, MDD, depressive disorder, depression, late-life depression, mood disorders, deep transcranial magnetic stimulation, deep TMS, dTMS, H coil, H-coil, older adults, H4-coil, H7-coil

7. Study Design

Primary Purpose

Health Services Research

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Model Description

This investigation is a one-way two-group between-subjects open-label design

Masking

None (Open Label)

Masking Description

This is an open label trial. Only study staff processing and analyzing the data will be fully blinded.

Allocation

Randomized

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Active H4-coil dTMS treatment

Arm Type

Experimental

Arm Title

Active H7-coil dTMS treatment

Arm Type

Experimental

Intervention Type

Device

Intervention Name(s)

Brainsway H4-Coil Deep TMS System

Intervention Description

Participants assigned to this arm will complete a 4-week course of 5 dTMS sessions per week (using the Brainsway H4-coil), for a total of 20 stimulation sessions. We will follow the standard Health Canada and FDA-approved protocol for depression: 18 Hz and 55 trains, for a total of 1980 pulses.

Intervention Type

Device

Intervention Name(s)

Brainsway H7-Coil Deep TMS System

Intervention Description

Participants assigned to this arm will complete a 4-week course of 5 dTMS sessions per week (using the Brainsway H7-coil), for a total of 20 stimulation sessions. We will follow the standard Health Canada and FDA-approved protocol for depression: 18 Hz and 55 trains, for a total of 1980 pulses.

Primary Outcome Measure Information:

Title

Feasibility criteria 1: Protocol completion

Description

Percentage of intervention sessions completed

Time Frame

4 weeks

Title

Feasibility criteria 2: Retention rate

Description

Percentage of participants who complete study once enrolled

Time Frame

4 weeks

Title

Feasibility criteria 3: Screening rates and capacity

Description

Number of participants (n) screened; n enrolled as a percentage of n screened monthly

Time Frame

4 weeks

Title

Feasibility criteria 4: Recruitment rate and capacity

Description

Total number of participants recruited and enrolled per month.

Time Frame

4 weeks

Title

Feasibility criteria 5: Duration of intervention and assessment processes

Description

Compared to estimated times, the actual mean times (in min) from start to finish for each dTMS intervention session and mean time (in hours) from start to finish for each visit.

Time Frame

4 weeks

Title

Feasibility criteria 5: Safety of H-coil dTMS treatment

Description

Time Frame

4 weeks

Title

Tolerability of H-coil dTMS treatment

Description

Percentage of participants withdrawn or terminated following enrollment due to adverse events

Time Frame

4 weeks

Secondary Outcome Measure Information:

Title

Change from baseline on the Hamilton Depression Rating Scale- 24 item (HDRS-24).

Description

Time Frame

4-weeks + 2-week follow-up

Title

Changes from baseline on the Geriatric Depression 30-item Scale (GDS-30)

Description

The GDS-30 will be used as a second measure of depression, a 30-item checklist, at the baseline (V1), midpoint (V10) and endpoint (V20) visits and at the 2-week follow-up.

Time Frame

4-weeks + 2-week follow-up

Title

Change from baseline on the General Anxiety Disorder- 7 item (GAD-7)

Description

Symptoms of anxiety will be assessed using this 7-item questionnaire at the baseline (V1), midpoint (V10) and endpoint (V20) visits and at the 2-week follow-up.

Time Frame

4-weeks + 2-week follow-up

Title

Change from baseline on the Pittsburgh Sleeping Quality Index (PSQI)

Description

Sleep will be monitored and assessed using the PSQI at the baseline (V1), midpoint (V10) and endpoint (V20) visits and at the 2-week follow-up.

Time Frame

4-weeks + 2-week follow-up

Title

Change from baseline on the Patient Health Questionnaire (PHQ - Somatic Symptoms)

Description

Somatic symptoms will be evaluated using the PHQ somatic inventory at the baseline (V1), midpoint (V10) and endpoint (V20) visits and at the 2-week follow-up

Time Frame

4-weeks + 2-week follow-up

Title

Changes from baseline in resting-state EEG

Description

Time Frame

4 weeks

Title

Changes from baseline in neurocognitive functioning (Repeatable Battery of Neuropsychological Status [RBANS])

Description

Neurocognitive performance will be assessed with the Repeatable Battery of Neuropsychological Status. Assessments will be completed at baseline (V1) and at post-treatment (V20).

Time Frame

4 weeks

10. Eligibility

Sex

All

Gender Based

Yes

Gender Eligibility Description

We will implement a sex equity approach by aiming at a 50/50% rate of male and female but allowing an imbalance of maximum 60/40% from either side.

Minimum Age & Unit of Time

60 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility Criteria

Central Contact Person:

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

Jane De Jesus, BSc

Phone

905-522-1155

dejesuj@mcmaster.ca

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

Dante Duarte, MD, MSc, PhD

Phone

905 522-1155

Ext

36782

duartedante@mcmaster.ca

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Dante Duarte, MD, MSc, PhD

Organizational Affiliation

Peter Boris Centre for Addictions Research at St. Joseph's Healthcare, Hamilton

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

James MacKillop, PhD

Organizational Affiliation

Peter Boris Centre for Addictions Research at St. Joseph's Healthcare, Hamilton

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

Emily MacKillop, PhD, ABPP-CN

Organizational Affiliation

Peter Boris Centre for Addictions Research at St. Joseph's Healthcare, Hamilton

Official's Role

Study Chair

Facility Information:

Facility Name

Peter Boris Centre for Addictions Research, St. Joseph's Healthcare Hamilton

City

Hamilton

State/Province

Ontario

ZIP/Postal Code

L9C 0E3

Country

Canada

Individual Site Status

Recruiting

12. IPD Sharing Statement

Learn more about this trial

Deep rTMS for Depression in Older Adults: A Pilot Study

We'll reach out to this number within 24 hrs