Neuromodulation in the Elderly Depressed: a Brain Imaging Pilot Study

Universitair Ziekenhuis Brussel

Status: Enrolling

Conditions: Depressive Disorder, Treatment-Resistant; Old Age

Treatments: Device: a Magstim Rapid2 Plus1 Magnetic Stimulator connected to a Brainsway H1 coil

Study type: Interventional

Funder types: Other

Identifiers

NCT04783103

2020/324

Details and patient eligibility

About

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

Full 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.

Enrollment: 44 estimated patients

Sex: All

Ages: 65+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

44 participants in 2 patient groups

Active adTMS

Active Comparator group

Description:

Subjects in the treatment arm receive 20 sessions of real adTMS . The sessions will be spread over the four succeeding days (5 sessions daily on Tuesday, Wednesday, Thursday and Friday).

Treatment:

Device: a Magstim Rapid2 Plus1 Magnetic Stimulator connected to a Brainsway H1 coil

Sham adTMS

Sham Comparator group

Description:

Subject in the control/Placebo/Sham arm receive 20 sessions of sham adTMS. The sessions will be spread over the four succeeding days (5 sessions daily on Tuesday, Wednesday, Thursday and Friday).

Treatment:

Device: a Magstim Rapid2 Plus1 Magnetic Stimulator connected to a Brainsway H1 coil