Back to resultsNeuromodulation in the Elderly Depressed: a Brain Imaging Pilot Study
Primary Purpose
Old Age, Depressive Disorder, Treatment-Resistant
Status
Recruiting
Phase
Not Applicable
Locations
Belgium
Study Type
Interventional
Intervention
a Magstim Rapid2 Plus1 Magnetic Stimulator connected to a Brainsway H1 coil
Sponsored by
About this trial
This is an interventional treatment trial for Old Age
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.
Sites / Locations
- UZ BrusselRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Sham Comparator
Arm Label
Active adTMS
Sham adTMS
Arm 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).
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).
Outcomes
Primary Outcome Measures
Clinical effect of adTMS (Changes in depression severity clinician-rated and self-report)
To investigate the effect of adTMS delivered by a H1 coil to the left Dorsolateral Prefrontal Cortex (DLPFC), as an add-on treatment, on depressive symptoms in a sample of elderly patients with MDD.-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. Response is reduction from baseline of ≥ 50% in the total score and remission is a total HAMD-17 score ≤ 7.
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.
measured by change in the Geriatric Depression Scale 15 item version (GDS-15) self-rating scale score.
Secondary Outcome Measures
Clinical effect of tDCS 17 item Hamilton Depression rating Scale score
To investigate the effect of tdCS delivered by a Sooma tDCS to the left Dorsolateral Prefrontal Cortex (DLPFC), as an add-on treatment, on depressive symptoms in a sample of elderly patients with MDD.-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. Response is reduction from baseline of ≥ 50% in the total score and remission is a total HAMD-17 score ≤ 7.
Clinical effect of tDCS Beck-Inventory of Depression-II score
To investigate the effect of tdCS delivered by a Sooma tDCS to the left Dorsolateral Prefrontal Cortex (DLPFC), as an add-on treatment, on depressive symptoms in a sample of elderly patients with MDD.-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.
Clinical effect of tDCS Geriatric Depression Scale 15 item version (GDS-15) self-rating scale score
To investigate the effect of tdCS delivered by a Sooma tDCS to the left Dorsolateral Prefrontal Cortex (DLPFC), as an add-on treatment, on depressive symptoms in a sample of elderly patients with MDD.-measured by change in the Geriatric Depression Scale 15 item version (GDS-15) self-rating scale score. Score of ≤6 is the criterion for remission and decrease of 50% from baseline is the criterion for treatment response.
maintenance effect of tDCS 17 item Hamilton Depression rating Scale score
To investigate the maintenance effect of tdCS delivered by a Sooma tDCS to the left Dorsolateral Prefrontal Cortex (DLPFC), as an add-on treatment, on depressive symptoms in a sample of elderly patients with MDD who responded to active adTMS measured by reduction from baseline of ≥ 50% in the total score in the 17 item Hamilton Depression rating Scale score. Maintenance effect occurs if the responders scores at day 15 remain or are lower on day 36.
maintenance effect of tDCS Beck-Inventory of Depression-II score
To investigate the maintenance effect of tdCS delivered by a Sooma tDCS to the left Dorsolateral Prefrontal Cortex (DLPFC), as an add-on treatment, on depressive symptoms in a sample of elderly patients with MDD who responded to active adTMS measured by reduction from baseline of ≥ 50% in the total score in the BDI-II score decrease of 50% from baseline in the Beck-Inventory of Depression-II score. Maintenance effect occurs if the responders scores at day 15 remain or are lower on day 36.
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
To investigate if the fMRI gender task provides an incidental measure of emotional processing and could be a better probe of limbic function, and it's predictive value for response to adTMS and/or tDCS.To look for change post-pre intervention in the fMRI gender task response.
effect on cognition MMSE
To investigate the effect of adTMS and tDCS on cognition as measured by increase in Mini Mental State examination scores.Scores range from 0 to 30, a score increase indicates improvement.
Incidence of Treatment-Emergent Adverse Events assessed with the Adverse Events questionnaire
To investigate the safety profile of adTMS and tDCS for elderly with MDD
effect on suicide risk as measured by change in C-SSRS
To investigate the effect of adTMS and tDCS on suicide risk of elderly patients with MDD.
effect on suicide risk as measured by change in BSI
To investigate the effect of adTMS and tDCS on suicide risk of elderly patients with MDD.
effect on the gut microbiome
To investigate the effect of neurostimulation on the gut microbiome in elderly with MDD.
possible neuroimaging biological markers for response
To investigate possible neurobiological markers for response to adTMS and/or tDCS by neuro imaging changes after adTMS and/or tDCS compared to baseline. Pre/Post changes in resting state fMRI en ASL (bloodflow) images.
Full Information
NCT ID
NCT04783103
First Posted
February 15, 2021
Last Updated
November 2, 2022
Sponsor
Universitair Ziekenhuis Brussel
1. Study Identification
Unique Protocol Identification Number
NCT04783103
Brief Title
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
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
May 7, 2021 (Actual)
Primary Completion Date
February 2025 (Anticipated)
Study Completion Date
July 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Universitair Ziekenhuis Brussel
4. Oversight
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
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Old Age, Depressive Disorder, Treatment-Resistant
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
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
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
All subjects will be assigned to one of the treatment arms by use of the top card from a stack of pre-coded cards which were prepared by an independent coder. The card has to be entered in machine in order to operate it and can be an activator of either sham or active treatment (both are integrated in and delivered by the same helmet coil.
Allocation
Randomized
Enrollment
44 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Active adTMS
Arm Type
Active Comparator
Arm 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).
Arm Title
Sham adTMS
Arm Type
Sham Comparator
Arm 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).
Intervention Type
Device
Intervention Name(s)
a Magstim Rapid2 Plus1 Magnetic Stimulator connected to a Brainsway H1 coil
Other Intervention Name(s)
Sooma tDCS (open label)
Intervention Description
3 weeks home use
Primary Outcome Measure Information:
Title
Clinical effect of adTMS (Changes in depression severity clinician-rated and self-report)
Description
To investigate the effect of adTMS delivered by a H1 coil to the left Dorsolateral Prefrontal Cortex (DLPFC), as an add-on treatment, on depressive symptoms in a sample of elderly patients with MDD.-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. Response is reduction from baseline of ≥ 50% in the total score and remission is a total HAMD-17 score ≤ 7.
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.
measured by change in the Geriatric Depression Scale 15 item version (GDS-15) self-rating scale score.
Time Frame
screening, Day 1 (+/-3d), Day 8 (+/-3d) ,Day 15 (+/-3d) Day 36 (+/-3d)
Secondary Outcome Measure Information:
Title
Clinical effect of tDCS 17 item Hamilton Depression rating Scale score
Description
To investigate the effect of tdCS delivered by a Sooma tDCS to the left Dorsolateral Prefrontal Cortex (DLPFC), as an add-on treatment, on depressive symptoms in a sample of elderly patients with MDD.-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. Response is reduction from baseline of ≥ 50% in the total score and remission is a total HAMD-17 score ≤ 7.
Time Frame
Day 15 (+/-3d) Day 36 (+/-3d)
Title
Clinical effect of tDCS Beck-Inventory of Depression-II score
Description
To investigate the effect of tdCS delivered by a Sooma tDCS to the left Dorsolateral Prefrontal Cortex (DLPFC), as an add-on treatment, on depressive symptoms in a sample of elderly patients with MDD.-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.
Time Frame
Day 15 (+/-3d) Day 36 (+/-3d)
Title
Clinical effect of tDCS Geriatric Depression Scale 15 item version (GDS-15) self-rating scale score
Description
To investigate the effect of tdCS delivered by a Sooma tDCS to the left Dorsolateral Prefrontal Cortex (DLPFC), as an add-on treatment, on depressive symptoms in a sample of elderly patients with MDD.-measured by change in the Geriatric Depression Scale 15 item version (GDS-15) self-rating scale score. Score of ≤6 is the criterion for remission and decrease of 50% from baseline is the criterion for treatment response.
Time Frame
Day 15 (+/-3d) Day 36 (+/-3d)
Title
maintenance effect of tDCS 17 item Hamilton Depression rating Scale score
Description
To investigate the maintenance effect of tdCS delivered by a Sooma tDCS to the left Dorsolateral Prefrontal Cortex (DLPFC), as an add-on treatment, on depressive symptoms in a sample of elderly patients with MDD who responded to active adTMS measured by reduction from baseline of ≥ 50% in the total score in the 17 item Hamilton Depression rating Scale score. Maintenance effect occurs if the responders scores at day 15 remain or are lower on day 36.
Time Frame
Day 15 (+/-3d) Day 36 (+/-3d)
Title
maintenance effect of tDCS Beck-Inventory of Depression-II score
Description
To investigate the maintenance effect of tdCS delivered by a Sooma tDCS to the left Dorsolateral Prefrontal Cortex (DLPFC), as an add-on treatment, on depressive symptoms in a sample of elderly patients with MDD who responded to active adTMS measured by reduction from baseline of ≥ 50% in the total score in the BDI-II score decrease of 50% from baseline in the Beck-Inventory of Depression-II score. Maintenance effect occurs if the responders scores at day 15 remain or are lower on day 36.
Time Frame
Day 15 (+/-3d) Day 36 (+/-3d)
Title
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
Description
To investigate if the fMRI gender task provides an incidental measure of emotional processing and could be a better probe of limbic function, and it's predictive value for response to adTMS and/or tDCS.To look for change post-pre intervention in the fMRI gender task response.
Time Frame
Day 1 (+/-3d), Day 8 (+/-3d)
Title
effect on cognition MMSE
Description
To investigate the effect of adTMS and tDCS on cognition as measured by increase in Mini Mental State examination scores.Scores range from 0 to 30, a score increase indicates improvement.
Time Frame
screening, Day 8 (+/-3d) ,Day 15 (+/-3d) Day 36 (+/-3d)
Title
Incidence of Treatment-Emergent Adverse Events assessed with the Adverse Events questionnaire
Description
To investigate the safety profile of adTMS and tDCS for elderly with MDD
Time Frame
Day 8 (+/-3d) ,Day 15 (+/-3d) Day 36 (+/-3d)
Title
effect on suicide risk as measured by change in C-SSRS
Description
To investigate the effect of adTMS and tDCS on suicide risk of elderly patients with MDD.
Time Frame
screening, Day 1 (+/-3d), Day 8 (+/-3d) ,Day 15 (+/-3d) Day 36 (+/-3d)
Title
effect on suicide risk as measured by change in BSI
Description
To investigate the effect of adTMS and tDCS on suicide risk of elderly patients with MDD.
Time Frame
screening, Day 1 (+/-3d), Day 8 (+/-3d) ,Day 15 (+/-3d) Day 36 (+/-3d)
Title
effect on the gut microbiome
Description
To investigate the effect of neurostimulation on the gut microbiome in elderly with MDD.
Time Frame
Day 1 (+/-3d), Day 8 (+/-3d) Day 36 (+/-3d)
Title
possible neuroimaging biological markers for response
Description
To investigate possible neurobiological markers for response to adTMS and/or tDCS by neuro imaging changes after adTMS and/or tDCS compared to baseline. Pre/Post changes in resting state fMRI en ASL (bloodflow) images.
Time Frame
Day 1 (+/-3d), Day 8 (+/-3d) Day 36 (+/-3d)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Dieter Zeeuws, MD
Phone
+324763459
Email
dieter.zeeuws@uzbrussel.be
First Name & Middle Initial & Last Name or Official Title & Degree
Chris Baeken, MD Phd
Phone
+324776425
Email
Chris.Baeken@uzbrussel.be
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dieter Zeeuws, MD
Organizational Affiliation
Universitair Ziekenhuis Brussel
Official's Role
Principal Investigator
Facility Information:
Facility Name
UZ Brussel
City
Jette
State/Province
Brussels
ZIP/Postal Code
1090
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dieter Zeeuws, MD
Phone
+324777722
Email
dieter.zeeuws@uzbrussel.be
First Name & Middle Initial & Last Name & Degree
Chris Baeken, MD PhD
Phone
324776425
Email
Chris.baeken@uzbrussel.be
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
All data will be disclosed after publication
IPD Sharing Time Frame
After publication of results
IPD Sharing Access Criteria
research
Learn more about this trial
Neuromodulation in the Elderly Depressed: a Brain Imaging Pilot Study
We'll reach out to this number within 24 hrs