Accelerated Deep TMS in the Elderly Depressed: A Brain Imaging Approach

With a growing number of elderly persons, geriatric depression - associated with important morbidity and mortality- is becoming a significant health problem. Given the risk of polypharmacy and increased side effects, alternative non pharmaceutical treatments such as repetitive transcranial magnetic stimulation (rTMS) may be a solution. Given recent positive results with accelerated rTMS in the elderly depressed, it is of interrest to continue to develop promising non-invasive treatment stimulations. The FDA approved deep brain TMS (dTMS) technique may be a promising option, targeting the brain underneath the neocortex with potentially better response and remission rates. Therefore, in a sham-controlled cross-over fashion, the investigators will treat 44 geriatric depressed patients with accelerated dTMS (5 sessions/day over 4 days only), and evaluate clinical efficacy and safety. Because new introduced rTMS paradigms should be rigorously neurobiologically examined before applying them on a regular basis, this research will include multimodal brain imaging techniques to elucidate the working mechanisms of this application in order to optimize treatment for such populations.

Study Overview

• Status: Withdrawn
• Conditions: Depression; Old Age
• Intervention / Treatment: Device: accelerated deep rTMS

Detailed Description

An initially double-blind sham-controlled cross-over study in geriatric depressed patients to investigate whether accelerated (a)dTMS is a safe and effective clinical option for this cohort. After the first week evaluations and MRI, there will be an open label phase in which patients who did receive active treatment in the first week will not receive any further rTMS sessions, those patients who had received sham however will get their active treatment in the second week. The independent researcher will use the treatment allocation list to inform the investigators if an active treatment faze is needed in the second week.

• Study Type: Interventional
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• In and outpatients (age 65 year or older) meeting Diagnostic and Statistical Manual of Mental Disorders (DSM 5) criteria for unipolar depression according 17-item Hamilton depression rating scale (HDRS-17) score of 17 or more, who failed to respond to at least one adequate course with an antidepressant medication trial, including the current one. Stable current antidepressant treatment (>6 weeks) will be continued during the stimulation.
• Able to read, understand and sign the Informed Consent Form.

Exclusion Criteria:

• Psychosis (exception: depression with psychotic features)
• A personal history of seizures or epilepsy, a history of seizures or epilepsy in first degree relatives and the presence of any known factor that can lower the seizure threshold (sleep deprivation, abuse substance, etc.), previous head injury and the presence of metallic implants in the cephalic region (e.g., aneurysm clips, shunts, stimulators, cochlear implants, electrodes) with the exception of dental fillings and the presence of cardiac pacemakers, neurostimulators, surgical clips or other electronic equipment, comorbidity with some neurological disorders: increased intracranial pressure, space-occupying lesion, history of stroke or transient ischemic attack, brain aneurysm.
• Patients with cognitive disturbances or dementia will not be included (Mini Mental State) < 24.
• Suicide attempt within 6 months before the start of the study or present risk of Suicide with the Columbia-Suicide Severity Rating Scale (C-SSRS).
• ECT exposure (current major depressive episode)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: active accelerated deep rTMS; Stimulation: We will use a Magstim Rapid2 Plus1 Magnetic Stimulator connected to a Brainsway H1 coil, which includes a sham option. In analogy to our former accelerated rTMS studies (2, 3), all patients will receive 20 dTMS sessions (5 sessions per day; 4 consecutive days) with a stimulation intensity of 120% of the subject's resting MT, as reported by Levkovitz et al.(4). Furthermore, we selected these FDA approved dTMS parameters, so that for one session each dTMS repetition includes 2-sec pulse trains separated by 20-sec inter-train intervals. Patients will receive 55 trains in each treatment session, for a total of 1980 pulses per session. This makes 9900 pulses/day, and in total 39600 pulses per treatment.	Device: accelerated deep rTMS; A Magstim Rapid2 Plus1 Magnetic Stimulator connected to the Brainsway dTMS system with the H1-coil investigational device (Brainsway Ltd, Jerusalem, Israel). The coil is situated inside a helmet to achieve effective cooling during stimulation. A sham coil is also included in the same helmet. The sham coil mimics scalp sensations and the acoustic artifact of the active stimulation without inducing neuronal activation.
Sham Comparator: sham; Built-in sham in the H1 Helmet (same device as active treatment)	Device: accelerated deep rTMS; A Magstim Rapid2 Plus1 Magnetic Stimulator connected to the Brainsway dTMS system with the H1-coil investigational device (Brainsway Ltd, Jerusalem, Israel). The coil is situated inside a helmet to achieve effective cooling during stimulation. A sham coil is also included in the same helmet. The sham coil mimics scalp sensations and the acoustic artifact of the active stimulation without inducing neuronal activation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	Number of participants with treatment-related adverse events as assessed by questionning the patient on each stimulation day	During 1 week (and 2 weeks for patients who received sham in the first week)
clinical efficacy measured by change in the 17 item Hamilton Depression rating Scale score.	for a total score between 0 and 48, the higher the total score the more severe the depression. Used measures are : for response (reduction from baseline of ≥ 50% in the total score) and remission (total HAMD-17 score ≤ 7)	from screening until last visit (week 4)
clinical efficacy measured by change in the Beck-Inventory of Depression-II score	for a total score between 0 and 63, the higher the total score the more severe the depression. A score of ≤9 is the criterion for remission, and BDI-II score decrease of 50% from baseline is the criterion for treatment response.	from screening until last visit (week 4)

Collaborators and Investigators

• Sponsor: Universitair Ziekenhuis Brussel
• Investigators: Study Director: Chris Baeken, MD Phd, Universitair Ziekenhuis Brussel

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2019
• Primary Completion (Anticipated): June 1, 2019
• Study Completion (Anticipated): June 1, 2019

Study Registration Dates

• First Submitted: June 3, 2019
• First Submitted That Met QC Criteria: June 5, 2019
• First Posted (Actual): June 7, 2019

Study Record Updates

• Last Update Posted (Actual): March 2, 2021
• Last Update Submitted That Met QC Criteria: February 25, 2021
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: repetitive Transcranial Magnetic Stimulation
• Additional Relevant MeSH Terms: Behavioral Symptoms; Depression
• Other Study ID Numbers: 2019-190 (Other Identifier: Republic of Turkey Ministry of Health)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No