4006-776-356 出国就医服务电话

免费获得国外相关药品，最快 1 个工作日回馈药物信息

出境医 / 临床实验 / Accelerated Deep TMS in the Elderly Depressed: A Brain Imaging Approach

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

Study Description
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.

Condition or disease Intervention/treatment Phase
Old Age Depression Device: accelerated deep rTMS Not Applicable

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 Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
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).
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Masking Description: unblinding will be done after the first week, in this way subjects receiving sham will have the opportunity to receive active treatment in the second week
Primary Purpose: Treatment
Official Title: Accelerated Deep TMS in the Elderly Depressed: A Brain Imaging Approach
Estimated Study Start Date : June 2019
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : June 2019
Arms and Interventions
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.
Outcome Measures
Primary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: During 1 week (and 2 weeks for patients who received sham in the first week) ]
    Number of participants with treatment-related adverse events as assessed by questionning the patient on each stimulation day

  2. clinical efficacy measured by change in the 17 item Hamilton Depression rating Scale score. [ Time Frame: from screening until last visit (week 4) ]
    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)

  3. clinical efficacy measured by change in the Beck-Inventory of Depression-II score [ Time Frame: from screening until last visit (week 4) ]
    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.


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   65 Years and older   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)
Contacts and Locations

Sponsors and Collaborators
Universitair Ziekenhuis Brussel
Investigators
Layout table for investigator information
Study Director: Chris Baeken, MD Phd Universitair Ziekenhuis Brussel
Tracking Information
First Submitted Date  ICMJE June 3, 2019
First Posted Date  ICMJE June 7, 2019
Last Update Posted Date March 2, 2021
Estimated Study Start Date  ICMJE June 2019
Estimated Primary Completion Date June 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 12, 2019)
  • Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: During 1 week (and 2 weeks for patients who received sham in the first week) ]
    Number of participants with treatment-related adverse events as assessed by questionning the patient on each stimulation day
  • clinical efficacy measured by change in the 17 item Hamilton Depression rating Scale score. [ Time Frame: from screening until last visit (week 4) ]
    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)
  • clinical efficacy measured by change in the Beck-Inventory of Depression-II score [ Time Frame: from screening until last visit (week 4) ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: June 5, 2019)
  • safety (registration of possible side effects) [ Time Frame: During 1 week (and 2 weeks for patients who received sham in the first week) ]
    Number of participants with treatment-related adverse events as assessed by questonning the patient on each stimulation day
  • clinical efficacy measured by The 17 item Hamilton Depression rating Scale [ Time Frame: from screening until last visit (week 4) ]
    used measures for response (reduction from baseline of ≥ 50% in the total score) and remission (total HAMD-17 score ≤ 7)
  • clinical efficacy measured by Beck-Inventory of Depression-II score [ Time Frame: from screening until last visit (week 4) ]
    score of ≤9 is the criterion for remission, and BDI-II score decrease of 50% from baseline is the criterion for treatment response.
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Accelerated Deep TMS in the Elderly Depressed: A Brain Imaging Approach
Official Title  ICMJE Accelerated Deep TMS in the Elderly Depressed: A Brain Imaging Approach
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
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).
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Masking Description:
unblinding will be done after the first week, in this way subjects receiving sham will have the opportunity to receive active treatment in the second week
Primary Purpose: Treatment
Condition  ICMJE
  • Old Age
  • Depression
Intervention  ICMJE 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.
Study Arms  ICMJE
  • 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.
    Intervention: Device: accelerated deep rTMS
  • Sham Comparator: sham
    Built-in sham in the H1 Helmet (same device as active treatment)
    Intervention: Device: accelerated deep rTMS
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: February 25, 2021) 		0
Original Estimated Enrollment  ICMJE
 (submitted: June 5, 2019) 		44
Estimated Study Completion Date  ICMJE June 2019
Estimated Primary Completion Date June 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 65 Years and older   (Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03978182
Other Study ID Numbers  ICMJE 2019-190
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Universitair Ziekenhuis Brussel
Study Sponsor  ICMJE Universitair Ziekenhuis Brussel
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Chris Baeken, MD Phd Universitair Ziekenhuis Brussel
PRS Account Universitair Ziekenhuis Brussel
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

治疗医院

新药特效药

前沿医讯