Clinical trial NCT04783103: Neuromodulation in the Elderly Depressed: a Brain Imaging Pilot Study
Official title: Neuromodulation in the Elderly Depressed: a Brain Im-aging Pilot Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Old Age
Depressive Disorder, Treatment-Resistant
Lead sponsor: Universitair Ziekenhuis Brussel
Sponsor class: OTHER
First posted: 2021-03-05
Enrollment: 44
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: In a sham-controlled randomized controlled trial, we will treat 44 geriatric depressed patients with accelerated dTMS (adTMS) (5 sessions/day over 4 days) and evaluate clinical efficacy and safety. One week after the last adTMS or sham treatment, all patients will have access to active treatment in a 3 week open label transcutaneous direct current stimulation (tDCS) with a home-use device. In this manner we can examine clinical effect of tDCS in the adTMS-sham group as well as the possible maintenance effect of tDCS in the adTMS active treatment group. Because newly introduced neuromodulation paradigms should go through profound neurobiological testing before applying them on a regular basis, this research will include multimodal brain imaging techniques to elucidate the working mechanisms of these applications in order to optimize response prediction and treatment
Primary purpose: TREATMENT

Brief summary: To evaluate safety and efficacy of an accelerated deep brain Transcranial Magnetic stimulation (adTMS) and transcutaneous direct current stimulation (tDCS) protocol in an elderly depressed patient population

Detailed description: 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) and transcutaneous direct current stimulation (tDCS) may offer a solution. Given our recent positive results with accelerated rTMS in the elderly depressed, we want to continue to develop 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 randomized controled trial, we will treat 44 geriatric depressed patients with accelerated dTMS (5 sessions/day over 4 days only), and evaluate clinical efficacy and safety. One week after the last adTMS or sham treatment, all patients will have access to active treatment in a 3 week open label transcutaneous direct current stimulation (tDCS) with a home-use device. In this manner we can examine clinnical effect of tDCS in the adTMS-sham group as well as the possible maintenance effect of tDCS in the adTMS active treatment group. Because new introduced neuromodulation 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 these applications in order to optimize response prediction and treatment. Gut microbes can influence human metabolism, nutrition, physiology and immune status. The "microbiota-gut-brain axis" entails a continues exchange of information between the gut and central nervous system. Several clinical and preclinical studies have emphasized the bidirectional role of microbiome disruption in depression and depression-like behavior. In the current project, we also will examine the effects of neurostimulation treatments on the gut microbiome.

Eligibility criteria: Inclusion Criteria:

* • In- and outpatients (age 65 year or older).

  * Meeting the 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.
  * Failed to respond to at least one adequate course with an antidepressant medication trial, including the current one.
  * Intention to continue the current (\>6 weeks) antidepressant treatment at a stable dose dur-ing the stimulation.
  * Benzodiazepines are permitted up to a maximum dose of 40 mg diazepam or equivalent. If the dosage has been recently changed, it should be stable for at least 2 weeks.
  * Able to read, understand and sign the Informed Consent Form.

Exclusion Criteria:

* • Psychosis (except 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, substance abuse, 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. The presence of cardiac pacemakers, neurostimulators, surgical clips or other electronic equipment, comorbidity with the following neurological disorders: increased intracranial pressure, space-occupying lesion, history of stroke or transient ischemic attack, brain aneurysm and any structural brain damage with increased risk for epilepsy detected with (study related) MRI.
  * Patients with cognitive disturbances or dementia (Mini Mental State) \< 24.
  * Suicide attempt within 6 months before the start of the study or present high risk of suicide per the investigator's clinical judgment and indicative response\* on the Columbia-Suicide Severity Rating Scale (C-SSRS) and 21-items Beck Scale for Suicide Ideation (BSI). \*'yes' on Item 5 (active suicidal ideation with specific plan and intent).
  * Any change in the habitual psychopharmacological agents will be considered as dropout.

Primary outcomes:
measure: Clinical effect of adTMS (Changes in depression severity clinician-rated and self-report)
timeFrame: screening, Day 1 (+/-3d), Day 8 (+/-3d) ,Day 15 (+/-3d) Day 36 (+/-3d)
Secondary outcomes:
measure: Clinical effect of tDCS 17 item Hamilton Depression rating Scale score
timeFrame: Day 15 (+/-3d) Day 36 (+/-3d)
measure: Clinical effect of tDCS Beck-Inventory of Depression-II score
timeFrame: Day 15 (+/-3d) Day 36 (+/-3d)
measure: Clinical effect of tDCS Geriatric Depression Scale 15 item version (GDS-15) self-rating scale score
timeFrame: Day 15 (+/-3d) Day 36 (+/-3d)
measure: maintenance effect of tDCS 17 item Hamilton Depression rating Scale score
timeFrame: Day 15 (+/-3d) Day 36 (+/-3d)
measure: maintenance effect of tDCS Beck-Inventory of Depression-II score
timeFrame: Day 15 (+/-3d) Day 36 (+/-3d)
measure: functional magnetic resonance imaging changes pre/post treatment in gender task as an incidental measure of emotional processing and probe of limbic function, and it's predictive value for response
timeFrame: Day 1 (+/-3d), Day 8 (+/-3d)
measure: effect on cognition MMSE
timeFrame: screening, Day 8 (+/-3d) ,Day 15 (+/-3d) Day 36 (+/-3d)
measure: Incidence of Treatment-Emergent Adverse Events assessed with the Adverse Events questionnaire
timeFrame: Day 8 (+/-3d) ,Day 15 (+/-3d) Day 36 (+/-3d)
measure: effect on suicide risk as measured by change in C-SSRS
timeFrame: screening, Day 1 (+/-3d), Day 8 (+/-3d) ,Day 15 (+/-3d) Day 36 (+/-3d)
measure: effect on suicide risk as measured by change in BSI
timeFrame: screening, Day 1 (+/-3d), Day 8 (+/-3d) ,Day 15 (+/-3d) Day 36 (+/-3d)
measure: effect on the gut microbiome
timeFrame: Day 1 (+/-3d), Day 8 (+/-3d) Day 36 (+/-3d)
measure: possible neuroimaging biological markers for response
timeFrame: Day 1 (+/-3d), Day 8 (+/-3d) Day 36 (+/-3d)
Other outcomes:
Locations:
city: Jette
country: Belgium
facility: UZ Brussel
state: Brussels
Study officials:
affiliation: Universitair Ziekenhuis Brussel
name: Dieter Zeeuws, MD
role: PRINCIPAL_INVESTIGATOR
References: