Clinical trial NCT03978182: Accelerated Deep TMS in the Elderly Depressed: A Brain Imaging Approach
Official title: Accelerated Deep TMS in the Elderly Depressed: A Brain Imaging Approach
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Old Age
Depression
Keywords: repetitive Transcranial Magnetic Stimulation
Lead sponsor: Universitair Ziekenhuis Brussel
Sponsor class: OTHER
First posted: 2019-06-07
Enrollment: 0
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: geriatric depressed patients after randomization at time T1 (on a Monday for MRI) will be divided into two groups to receive 20 sessions of real or sham adTMS treatment respectively. A given patient who first received active treatment will not receive sham, because of the carry-over effects; a patient who first received sham treatment now receives active adTMS in an open phase. This treatment will be spread over the four succeeding afternoons (5 daily sessions). In the second week, strictly the same treatment schedule will be followed but with the reverse order. A second brain imaging assessment will be performed exactly 1 week after the first week (time T2) and a third time scan exactly after 2 weeks (time T3).
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: During 1 week (and 2 weeks for patients who received sham in the first week)
measure: clinical efficacy measured by change in the 17 item Hamilton Depression rating Scale score.
timeFrame: from screening until last visit (week 4)
measure: clinical efficacy measured by change in the Beck-Inventory of Depression-II score
timeFrame: from screening until last visit (week 4)
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Universitair Ziekenhuis Brussel
name: Chris Baeken, MD Phd
role: STUDY_DIRECTOR
References: