Ignite Creation Date:
2024-10-26 @ 3:40 PM
Last Modification Date:
2024-10-26 @ 3:40 PM
Study NCT ID:
NCT06599099
Status:
RECRUITING
Last Update Posted:
None
First Post:
2024-08-28
Brief Title:
Deep Brain Stimulation of Treatment-Resistant Bipolar Depression
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Building Mood State Classifiers to Inform Deep Brain Stimulation of Treatment-Resistant Bipolar Depression
Status:
RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
DBS in TRBD
Brief Summary:
This study is only enrolling at Baylor College of Medicine The other research locations listed serve to support data analysis only
This research study is to investigate the use of technology called Deep Brain Stimulation DBS to potentially improve Treatment-Resistant Bipolar Depression TRBD symptoms in patients with severe cases DBS involves the surgical implantation of leads and electrodes into specific areas of the brain which are thought to influence the disease A pack implanted in the chest called the neurotransmitter keeps the electrical current coursing to the brain through a wire that connects the neurotransmitter and electrodes It is believed DBS may restore balance to dysfunctional brain circuitry implicated in TRBD The goal of this study is to enhance current approaches to DBS targeting in the brain and to use a novel approach to find a better and more reliable system for TRBD treatment
Its important for participants to understand that this is an investigational study where there could be a lack of effectiveness in improving TRBD symptoms There may be no directly benefit from taking part in this study
This study is expected to last 20 months and involves 3 main steps
1 Medical psychiatric and cognitive evaluations
2 Implantation of a brain stimulation system
3 Follow up after implantation of device including programming recording and psychiatric testing
There are risks and benefits to this study which need to be considered when deciding to participate or not Some of the risks are from surgery the DBS device and programming the tests involved and potential loss of confidentiality as well as other unknown risks
Some of the more serious risks involved in this study and the percentage that they occur
1 Bleeding inside the Brain 1 to 2 percent
2 Infection from the procedures 3 percent
3 Seizure caused from the procedures 12 percent
However the benefit of this study is that it may help relieve or decrease TRBD symptoms This form of treatment has shown to reduce symptom severity in other cases This could potentially improve quality of life and activities in daily routines There is also a potential benefit to society in that the data the investigators will obtain from this study may help increase the understanding of the mechanisms underlying TRBD symptoms as well as enhanced Deep Brain Stimulation techniques
Study participation is expected to last 20 months from the time the DBS device is activated and should include approximately 23 visits These visits also include 8 separate 24 hour stays at the Menninger NeuroBehvaioral Monitoring Unit NBU These 24-hour sessions will occur at multiple points throughout the study 1 week prior to surgery the week preceding device activation the week following activation then after 2 weeks 4 weeks 6 months 9 months and 12 months Participants will need to stay locally for the week of the NBU stay typically Monday through Friday
Study visits will include clinician administered assessments and questionnaires subject reported assessments neuropsychological testing and mobile behavioral assessments which will occur around 23 visits over the course of 20 months
This research study is to investigate the use of technology called Deep Brain Stimulation DBS to potentially improve Treatment-Resistant Bipolar Depression TRBD symptoms in patients with severe cases DBS involves the surgical implantation of leads and electrodes into specific areas of the brain which are thought to influence the disease A pack implanted in the chest called the neurotransmitter keeps the electrical current coursing to the brain through a wire that connects the neurotransmitter and electrodes It is believed DBS may restore balance to dysfunctional brain circuitry implicated in TRBD The goal of this study is to enhance current approaches to DBS targeting in the brain and to use a novel approach to find a better and more reliable system for TRBD treatment
Its important for participants to understand that this is an investigational study where there could be a lack of effectiveness in improving TRBD symptoms There may be no directly benefit from taking part in this study
This study is expected to last 20 months and involves 3 main steps
1 Medical psychiatric and cognitive evaluations
2 Implantation of a brain stimulation system
3 Follow up after implantation of device including programming recording and psychiatric testing
There are risks and benefits to this study which need to be considered when deciding to participate or not Some of the risks are from surgery the DBS device and programming the tests involved and potential loss of confidentiality as well as other unknown risks
Some of the more serious risks involved in this study and the percentage that they occur
1 Bleeding inside the Brain 1 to 2 percent
2 Infection from the procedures 3 percent
3 Seizure caused from the procedures 12 percent
However the benefit of this study is that it may help relieve or decrease TRBD symptoms This form of treatment has shown to reduce symptom severity in other cases This could potentially improve quality of life and activities in daily routines There is also a potential benefit to society in that the data the investigators will obtain from this study may help increase the understanding of the mechanisms underlying TRBD symptoms as well as enhanced Deep Brain Stimulation techniques
Study participation is expected to last 20 months from the time the DBS device is activated and should include approximately 23 visits These visits also include 8 separate 24 hour stays at the Menninger NeuroBehvaioral Monitoring Unit NBU These 24-hour sessions will occur at multiple points throughout the study 1 week prior to surgery the week preceding device activation the week following activation then after 2 weeks 4 weeks 6 months 9 months and 12 months Participants will need to stay locally for the week of the NBU stay typically Monday through Friday
Study visits will include clinician administered assessments and questionnaires subject reported assessments neuropsychological testing and mobile behavioral assessments which will occur around 23 visits over the course of 20 months
Detailed Description:
This study is only enrolling at Baylor College of Medicine The other research locations listed serve to support data analysis only
Enrollment A subject is considered enrolled upon signing informed consent and deemed eligible to be screened by the investigator The informed consent process may include discussions with the patients family and referring clinician
Screening Potential subjects meeting inclusionexclusion criteria and willing to participate in the study as demonstrated by signing the informed consent will be enrolled in the study and undergo a screening and baseline visit Visit 1 and Visit 2 spaced over an approximate 1 month period Diagnostic and screening ratings are completed followed by complete medical neurological and neurosurgical evaluations Final selection of candidates will be made by consensus of the multi-disciplinary investigator team
Surgical Procedures All patients will be implanted with bilateral leads targeting the VCVS using the investigators previously described robotic DBS workflow In brief preoperative high-resolution MRI 3D T1-weighted with and without contrast and 3D CT will be obtained and uploaded to the ROSA Zimmer Biomet planning station Images will be merged and the AC posterior commissure and interhemispheric plane will be marked as is routinely done for stereotactic procedures The investigatorswill plan two trajectories for each hemisphere and use intraoperative awake testing to validate the optimal target One trajectory will be planned just anterior to AC VCVS the other just posterior bed nucleus stria terminalis BNST The investigatorshave successfully implemented intraoperative behavioral testing to adjudicate between VCVS and BNST in patients with treatment resistant OCD Both trajectories will be planned such that the deepest contact is at the whitegray matter junction ie VCVS for the anterior trajectory BNST for the posterior trajectory The trajectory will follow the coronal contour of the anterior limb of the internal capsule ALIC
The investigators will use the postcontrast scan to ensure lack of vessel collision A stereotactic frame Leksell model G Elekta will be placed under local anesthesia Under light sedation to minimize movement a fluoroscopic CT scan O-arm 2 Medtronic will be obtained and merged with the other image sets on the robotic navigation system Using the frame skull pins as bone fiducials the robot will be registered to the fixed head and entry points marked according to preoperative planning The head will be prepped and draped to allow for awake evaluation of the patient later in the procedure The fluoroscopic CT will be draped into the field so that an intraoperative scan can be easily acquired A single burr hole on each side will be drilled The burr hole will be large enough to accommodate both trajectories
Intraoperative Behavioral Testing Lead securing devices will be installed bilaterally and sedation stopped for intraoperative testing A cannula 0 mm above target 192 mm length Alpha Omega will be introduced to the first target as usual in DBS surgery In general the left VCVS will be chosen as the first target In cases in which the BNST is the safer trajectory this target will be tested first A DBS lead will be placed and the cannula withdrawn to expose the contacts Intraoperative evaluation will be conducted by a psychiatrist WKG including a quick monopolar survey of all 4 contacts up to 5 mA The investigators will ask whether the patient experiences any change in mood energy or anxiety while evaluating for positive valence PV affect improved mood increased energy and reduced anxiety on all contacts and for adverse effects increased anxiety worsened mood or other negative valence NV response If a strong consistent PV is produced during the monopolar survey and no side effects are evident the lead will be secured in that position If no PV is evident or if NV is produced or other side effects are present the lead will be removed and the cannula repositioned to the second target The investigators will then conduct another monopolar review at the second target in the same manner Following stimulation of the second target the neurosurgery and psychiatry teams will discuss the results to choose the final location of the lead The patient will be blinded to stimulation target amplitude and side The DBS system will be activated approximately 2 weeks following surgery during the first programming visit
NeuroBehavioral Monitoring Unit NBU To capture high-density neural data coupled with multimodal measures including sleep subjects will spend 24 hours in the NBU - located at The Menninger Clinics main campus in Houston - at multiple time points in the study
1 week prior to surgery and week preceding activation and
2 week following activation then after 2 weeks 4 weeks 6 months 9 months and 12 months
The total days in NBU per subject is 8 Each of those visits will correspond to a period in-situ which will generally be 5 days long Monday through Friday including one day in the NBU These are times when subjects will reside locally due to frequency of assessments or need for high-density recordings in NBU In general subjects will be asked to stay locally in the greater Houston area for the first 4 weeks following activation To support recording neural time-domain local field potentials streaming while in the NBU a Percept clinician programmer will be placed inside the room and configured to stream from the subjects implanted device for the duration of the participants stay A research coordinator will be responsible for restarting streaming sessions every eight hours ensuring the patients device stays charged and ensuring the tablet stays connected as the patient moves through common spaces in on the Menninger campus The clinician programmer tablet will be physically secured such that the subject cannot mistakenly tamper with it Within the NBU the subject will be asked to wear the mobile sensing systems Apple watch Oura ring and audioband to be deployed in the participants home for sensor performance characterization
Multimodal Biobehavioral Measurement Unlike movement disorders where the effect of stimulation can be acquired near instantaneously during programming psychological state fluctuations require monitoring over days or weeks which can be best accomplished using wearable systems in naturalistic settings The Rune patient app collects patient reported events diary info and wearable data and pushes it up to the cloud StrivePD portal The neural data need to be uploaded to the Rune StrivePD web portal for integrating and synching the neural data with the behavioral data The Percept-RC sensing capabilities will allow the investigators to collect high density neural data in the clinic and NBU and less dense but chronic neural data collected in parallel with ecological data obtained outside the clinic Passive and active eg EMA survey pushes behavioral data will be collected throughout the clinical trial including baseline before surgery and baseline pre-activation following surgery
Weeks -8-0 Screening and Baseline The following Clinician-administered assessments will take place Vital Signs Structured Interview SCID-5 SCID-5-PD Personality Disorders Montgomery Asberg Rating Scale MADRS Global SeverityChange CGI-SI Young Mania Rating Scale YMRS56 Suicidality C-SSRS Anxiety HAM-A Medication Recommendation Tracking Form MRTF Side-Effects PRISE
The following Subject Reported assessments will take place Depression QIDS-SR Quality of Life Scale QOLS Sheehan Disability SDS Barratt Impulsiveness Scale BIS Altman Self-Rating Mania Scale ASRM Insomnia Severity Index ISI Positive and Negative Affect Schedule PANAS Morning-Eveningness Questionnaire MEQ Internal State Scale ISS
The following Medical and Laboratory Testing will take place Physical Exam Vital Signs ECG UA CMP CBC PTPTTINR Hepatitis serology pregnancy tox screen Brain Imaging 3T sMRI DTI MEG rsfMRI
All blood draws are for clinical purposes ONLY and not research
The following Neuropsychological Testing Neuropsych will occur MMSE HVLT-R BVMT-R MoCA TOPF Weschler Adult Intelligence Scale IV Edition Digit Span Coding Similarities Information Visual Puzzles Trails A B WCST-64Rey-Osterrieth Complex Figure DKEFS lexical and semantic fluency STROOP BDI-II PSWQ OCI-R Millon Behavioral Medicine diagnostic MBMD baseline only Alternate forms for follow-up testing
The following Behavioral Tasks will occur Probabilistic Reward Task PRT and Immediate Memory Task IMT will be given at baseline Mobile biobehavioral measures eg Rune app ingested data from wearables peripherals self-reports Administer 5-10-minute Ecological Momentary Assessment EMA sessions will be triggered starting at baseline and throughout the course of the study Peripherals and wearables for activity and sleep monitoring will be provided for continuous use
Neurobehavioral Unit Will be in-situ staying locally during much of this time and spend one 24-hour period in in a clinical monitoring environment for highdensity streaming coupled with multi-modal behavioral measures including computer vision for affect and activity analysis speech analysis peripherals and wearables for activity and sleep Polysomnography at baseline overnight stay at NBU to conduct baseline sleep study for validation of concurrent and subsequent Oura Ring sleep monitoring
This will be NBU visit 1 of 8
DBS SURGERY VISIT CT scans will be performed prior to during and after surgery The DBS System Implantation of bilateral VCVS current steering electrodes
Week 1-2 Following one week recovery seen for repeat baseline assessments pre-DBS activation These include
Clinician-administered Vital Signs MADRS CGIS YMRS C-SSRSHAM-A MRTF PRISE Subject Reported QIDS-SR QOLS SDS BIS ASRM PANAS MEQ ISS Medical and Laboratory Testing Repeat MEG rsfMRI
Neuropsychological Testing Neuropsych Repeat the neuropsych battery defined in the screeningbaseline period Behavioral Tasks PRT and IMT
Mobile Biobehavioral measures ongoing data collection through continuous use of wearable sensors peripherals and EMA
NeuroBehavioral Unit two 24-hour periods in NBU This will include NBU visit 2 of 8
Week 2 following surgery Following two week recovery subject will be seen for baseline assessments and system activation of theDBS device
Repeat Assessments
Clinician-administered Vital Signs MADRS CGIS YMRS C-SSRS HAM-A MRTF PRISE
Subject Reported QIDS-SR QOLS SDS BIS ASRM PANAS MEQ ISS
Neuropsychological Testing Neuropsych Repeat the neuropsych battery defined in the screeningbaseline period
Behavioral Tasks PRT and IMT
Mobile Biobehavioral measures ongoing data collection through continuous use of wearable sensors peripherals and EMA
NeuroBehavioral Unit Will be in-situ staying locally during much of this time and spend one 24-hour period in the NBU This will include NBU visit 3 of 8
Week 3-8 Following two weeks recovery seen for initial DBS programming session for monopolar survey The subject will be seen every 1-2 weeks for programming optimization
Repeat assessments
Clinician-administered Vital Signs MADRS CGIS YMRS C-SSRS HAM-A MRTF PRISE Subject Reported QIDS-SR QOLS SDS BIS ASRM PANAS MEQ ISS
Neuropsychological Testing Neuropsych Likert-like scales assessing mood anxiety and energy will be given before and after programming Behavioral Tasks PRT and IMT at month 1
Mobile Biobehavioral measures ongoing data collection through continuous use of wearable sensors peripherals and EMA Begin collection of LFPs to be synchronized other measures for offline analysis
Neurobehavioral Unit One 24-hour stay in NBU NBU visits 4 and 5 out of 8 will occur during this time
Months 2-9 These will include once a month visits in order to optimize chronic DBS programming for efficacy and safety
Repeat assessments
Clinician-administered Vital Signs MADRS CGIS YMRS C-SSRS HAM-A MRTF PRISE
Subject Reported QIDS-SR QOLS SDS BIS ASRM PANAS MEQ ISS Medical and Laboratory Testing Repeat MEG rsfMRI at end-of-month 6
Neuropsychological Testing Neuropsych Repeat the neuropsych battery defined in the screeningbaseline period
Behavioral Tasks PRT and IMT
Mobile Biobehavioral measures ongoing data collection through continuous use of wearable sensors peripherals and EMA
NeuroBehavioral Unit Will be in-situ staying locally during much of this time and spend one 24-hour period in the NBU
This will be NBU visit 6 of 8
Month 9 visit At this visit the team will determine if subject meets responder criteria
Repeat Assessments
Clinician-administered Vital Signs MADRS CGIS YMRS C-SSRS HAM-A MRTF PRISE
Subject Reported QIDS-SR QOLS SDS BIS ASRM PANAS MEQ ISS
Medical and Laboratory Testing Repeat MEG rsfMRI
Neuropsychological Testing Neuropsych Repeat post-op baseline Neuropsych battery
Behavioral Tasks PRT and IMT at end-of-month 9
Mobile Biobehavioral measures ongoing data collection through continuous use of wearable sensors peripherals EMA and neural LFPs
NeuroBehavioral Unit Will be in-situ staying locally during much of this time and spend one 24-hour period in the NBU
This will be NBU visit 7 of 8
Months 9-12 Continuation of monthly visits for key clinical evaluations
Repeat Assessments
Clinician-administered Vital Signs MADRS CGIS YMRS C-SSRS HAM-A MRTF PRISE
Subject Reported QIDS-SR QOLS SDS BIS ASRM PANAS MEQ ISS
Mobile Biobehavioral measures ongoing data collection through continuous use of wearable sensors peripherals EMA and neural LFPs
End Month 12 Begin 1 month withdrawal period The DBS system will be turned off completely at some point during this gradual taper period The study doctor will make the clinical decision whether to restart stimulation
Repeat Assessments
Clinician-administered Vital Signs MADRS CGIS YMRS C-SSRS HAM-A MRTF PRISE
Subject Reported QIDS-SR QOLS SDS BIS ASRM PANAS MEQ ISS
Medical and Laboratory Testing Repeat MEG rsfMRI
Behavioral Tasks PRT and IMT at end-of-month 12 NeuroBehavioral Unit Will be in-situ staying locally during much of this time and spend one 24-hour period in the NBU
This will be NBU visit 8 of 8
Months 13-20 The team and subject will make the clinical decision whether to reinstate or deactive DBS following discontinuation phase
Repeat Assessments
Clinician-administered Vital Signs MADRS CGIS YMRS C-SSRS HAM-A MRTF PRISE
Subject Reported QIDS-SR QOLS SDS BIS ASRM PANAS MEQ ISS
Month 20 Last set of formal study visits All evaluations and labs will be repeated
Clinician-administered Vital Signs MADRS CGIS YMRS C-SSRS HAM-A MRTF PRISE
Subject Reported QIDS-SR QOLS SDS BIS ASRM PANAS MEQ ISS
Enrollment A subject is considered enrolled upon signing informed consent and deemed eligible to be screened by the investigator The informed consent process may include discussions with the patients family and referring clinician
Screening Potential subjects meeting inclusionexclusion criteria and willing to participate in the study as demonstrated by signing the informed consent will be enrolled in the study and undergo a screening and baseline visit Visit 1 and Visit 2 spaced over an approximate 1 month period Diagnostic and screening ratings are completed followed by complete medical neurological and neurosurgical evaluations Final selection of candidates will be made by consensus of the multi-disciplinary investigator team
Surgical Procedures All patients will be implanted with bilateral leads targeting the VCVS using the investigators previously described robotic DBS workflow In brief preoperative high-resolution MRI 3D T1-weighted with and without contrast and 3D CT will be obtained and uploaded to the ROSA Zimmer Biomet planning station Images will be merged and the AC posterior commissure and interhemispheric plane will be marked as is routinely done for stereotactic procedures The investigatorswill plan two trajectories for each hemisphere and use intraoperative awake testing to validate the optimal target One trajectory will be planned just anterior to AC VCVS the other just posterior bed nucleus stria terminalis BNST The investigatorshave successfully implemented intraoperative behavioral testing to adjudicate between VCVS and BNST in patients with treatment resistant OCD Both trajectories will be planned such that the deepest contact is at the whitegray matter junction ie VCVS for the anterior trajectory BNST for the posterior trajectory The trajectory will follow the coronal contour of the anterior limb of the internal capsule ALIC
The investigators will use the postcontrast scan to ensure lack of vessel collision A stereotactic frame Leksell model G Elekta will be placed under local anesthesia Under light sedation to minimize movement a fluoroscopic CT scan O-arm 2 Medtronic will be obtained and merged with the other image sets on the robotic navigation system Using the frame skull pins as bone fiducials the robot will be registered to the fixed head and entry points marked according to preoperative planning The head will be prepped and draped to allow for awake evaluation of the patient later in the procedure The fluoroscopic CT will be draped into the field so that an intraoperative scan can be easily acquired A single burr hole on each side will be drilled The burr hole will be large enough to accommodate both trajectories
Intraoperative Behavioral Testing Lead securing devices will be installed bilaterally and sedation stopped for intraoperative testing A cannula 0 mm above target 192 mm length Alpha Omega will be introduced to the first target as usual in DBS surgery In general the left VCVS will be chosen as the first target In cases in which the BNST is the safer trajectory this target will be tested first A DBS lead will be placed and the cannula withdrawn to expose the contacts Intraoperative evaluation will be conducted by a psychiatrist WKG including a quick monopolar survey of all 4 contacts up to 5 mA The investigators will ask whether the patient experiences any change in mood energy or anxiety while evaluating for positive valence PV affect improved mood increased energy and reduced anxiety on all contacts and for adverse effects increased anxiety worsened mood or other negative valence NV response If a strong consistent PV is produced during the monopolar survey and no side effects are evident the lead will be secured in that position If no PV is evident or if NV is produced or other side effects are present the lead will be removed and the cannula repositioned to the second target The investigators will then conduct another monopolar review at the second target in the same manner Following stimulation of the second target the neurosurgery and psychiatry teams will discuss the results to choose the final location of the lead The patient will be blinded to stimulation target amplitude and side The DBS system will be activated approximately 2 weeks following surgery during the first programming visit
NeuroBehavioral Monitoring Unit NBU To capture high-density neural data coupled with multimodal measures including sleep subjects will spend 24 hours in the NBU - located at The Menninger Clinics main campus in Houston - at multiple time points in the study
1 week prior to surgery and week preceding activation and
2 week following activation then after 2 weeks 4 weeks 6 months 9 months and 12 months
The total days in NBU per subject is 8 Each of those visits will correspond to a period in-situ which will generally be 5 days long Monday through Friday including one day in the NBU These are times when subjects will reside locally due to frequency of assessments or need for high-density recordings in NBU In general subjects will be asked to stay locally in the greater Houston area for the first 4 weeks following activation To support recording neural time-domain local field potentials streaming while in the NBU a Percept clinician programmer will be placed inside the room and configured to stream from the subjects implanted device for the duration of the participants stay A research coordinator will be responsible for restarting streaming sessions every eight hours ensuring the patients device stays charged and ensuring the tablet stays connected as the patient moves through common spaces in on the Menninger campus The clinician programmer tablet will be physically secured such that the subject cannot mistakenly tamper with it Within the NBU the subject will be asked to wear the mobile sensing systems Apple watch Oura ring and audioband to be deployed in the participants home for sensor performance characterization
Multimodal Biobehavioral Measurement Unlike movement disorders where the effect of stimulation can be acquired near instantaneously during programming psychological state fluctuations require monitoring over days or weeks which can be best accomplished using wearable systems in naturalistic settings The Rune patient app collects patient reported events diary info and wearable data and pushes it up to the cloud StrivePD portal The neural data need to be uploaded to the Rune StrivePD web portal for integrating and synching the neural data with the behavioral data The Percept-RC sensing capabilities will allow the investigators to collect high density neural data in the clinic and NBU and less dense but chronic neural data collected in parallel with ecological data obtained outside the clinic Passive and active eg EMA survey pushes behavioral data will be collected throughout the clinical trial including baseline before surgery and baseline pre-activation following surgery
Weeks -8-0 Screening and Baseline The following Clinician-administered assessments will take place Vital Signs Structured Interview SCID-5 SCID-5-PD Personality Disorders Montgomery Asberg Rating Scale MADRS Global SeverityChange CGI-SI Young Mania Rating Scale YMRS56 Suicidality C-SSRS Anxiety HAM-A Medication Recommendation Tracking Form MRTF Side-Effects PRISE
The following Subject Reported assessments will take place Depression QIDS-SR Quality of Life Scale QOLS Sheehan Disability SDS Barratt Impulsiveness Scale BIS Altman Self-Rating Mania Scale ASRM Insomnia Severity Index ISI Positive and Negative Affect Schedule PANAS Morning-Eveningness Questionnaire MEQ Internal State Scale ISS
The following Medical and Laboratory Testing will take place Physical Exam Vital Signs ECG UA CMP CBC PTPTTINR Hepatitis serology pregnancy tox screen Brain Imaging 3T sMRI DTI MEG rsfMRI
All blood draws are for clinical purposes ONLY and not research
The following Neuropsychological Testing Neuropsych will occur MMSE HVLT-R BVMT-R MoCA TOPF Weschler Adult Intelligence Scale IV Edition Digit Span Coding Similarities Information Visual Puzzles Trails A B WCST-64Rey-Osterrieth Complex Figure DKEFS lexical and semantic fluency STROOP BDI-II PSWQ OCI-R Millon Behavioral Medicine diagnostic MBMD baseline only Alternate forms for follow-up testing
The following Behavioral Tasks will occur Probabilistic Reward Task PRT and Immediate Memory Task IMT will be given at baseline Mobile biobehavioral measures eg Rune app ingested data from wearables peripherals self-reports Administer 5-10-minute Ecological Momentary Assessment EMA sessions will be triggered starting at baseline and throughout the course of the study Peripherals and wearables for activity and sleep monitoring will be provided for continuous use
Neurobehavioral Unit Will be in-situ staying locally during much of this time and spend one 24-hour period in in a clinical monitoring environment for highdensity streaming coupled with multi-modal behavioral measures including computer vision for affect and activity analysis speech analysis peripherals and wearables for activity and sleep Polysomnography at baseline overnight stay at NBU to conduct baseline sleep study for validation of concurrent and subsequent Oura Ring sleep monitoring
This will be NBU visit 1 of 8
DBS SURGERY VISIT CT scans will be performed prior to during and after surgery The DBS System Implantation of bilateral VCVS current steering electrodes
Week 1-2 Following one week recovery seen for repeat baseline assessments pre-DBS activation These include
Clinician-administered Vital Signs MADRS CGIS YMRS C-SSRSHAM-A MRTF PRISE Subject Reported QIDS-SR QOLS SDS BIS ASRM PANAS MEQ ISS Medical and Laboratory Testing Repeat MEG rsfMRI
Neuropsychological Testing Neuropsych Repeat the neuropsych battery defined in the screeningbaseline period Behavioral Tasks PRT and IMT
Mobile Biobehavioral measures ongoing data collection through continuous use of wearable sensors peripherals and EMA
NeuroBehavioral Unit two 24-hour periods in NBU This will include NBU visit 2 of 8
Week 2 following surgery Following two week recovery subject will be seen for baseline assessments and system activation of theDBS device
Repeat Assessments
Clinician-administered Vital Signs MADRS CGIS YMRS C-SSRS HAM-A MRTF PRISE
Subject Reported QIDS-SR QOLS SDS BIS ASRM PANAS MEQ ISS
Neuropsychological Testing Neuropsych Repeat the neuropsych battery defined in the screeningbaseline period
Behavioral Tasks PRT and IMT
Mobile Biobehavioral measures ongoing data collection through continuous use of wearable sensors peripherals and EMA
NeuroBehavioral Unit Will be in-situ staying locally during much of this time and spend one 24-hour period in the NBU This will include NBU visit 3 of 8
Week 3-8 Following two weeks recovery seen for initial DBS programming session for monopolar survey The subject will be seen every 1-2 weeks for programming optimization
Repeat assessments
Clinician-administered Vital Signs MADRS CGIS YMRS C-SSRS HAM-A MRTF PRISE Subject Reported QIDS-SR QOLS SDS BIS ASRM PANAS MEQ ISS
Neuropsychological Testing Neuropsych Likert-like scales assessing mood anxiety and energy will be given before and after programming Behavioral Tasks PRT and IMT at month 1
Mobile Biobehavioral measures ongoing data collection through continuous use of wearable sensors peripherals and EMA Begin collection of LFPs to be synchronized other measures for offline analysis
Neurobehavioral Unit One 24-hour stay in NBU NBU visits 4 and 5 out of 8 will occur during this time
Months 2-9 These will include once a month visits in order to optimize chronic DBS programming for efficacy and safety
Repeat assessments
Clinician-administered Vital Signs MADRS CGIS YMRS C-SSRS HAM-A MRTF PRISE
Subject Reported QIDS-SR QOLS SDS BIS ASRM PANAS MEQ ISS Medical and Laboratory Testing Repeat MEG rsfMRI at end-of-month 6
Neuropsychological Testing Neuropsych Repeat the neuropsych battery defined in the screeningbaseline period
Behavioral Tasks PRT and IMT
Mobile Biobehavioral measures ongoing data collection through continuous use of wearable sensors peripherals and EMA
NeuroBehavioral Unit Will be in-situ staying locally during much of this time and spend one 24-hour period in the NBU
This will be NBU visit 6 of 8
Month 9 visit At this visit the team will determine if subject meets responder criteria
Repeat Assessments
Clinician-administered Vital Signs MADRS CGIS YMRS C-SSRS HAM-A MRTF PRISE
Subject Reported QIDS-SR QOLS SDS BIS ASRM PANAS MEQ ISS
Medical and Laboratory Testing Repeat MEG rsfMRI
Neuropsychological Testing Neuropsych Repeat post-op baseline Neuropsych battery
Behavioral Tasks PRT and IMT at end-of-month 9
Mobile Biobehavioral measures ongoing data collection through continuous use of wearable sensors peripherals EMA and neural LFPs
NeuroBehavioral Unit Will be in-situ staying locally during much of this time and spend one 24-hour period in the NBU
This will be NBU visit 7 of 8
Months 9-12 Continuation of monthly visits for key clinical evaluations
Repeat Assessments
Clinician-administered Vital Signs MADRS CGIS YMRS C-SSRS HAM-A MRTF PRISE
Subject Reported QIDS-SR QOLS SDS BIS ASRM PANAS MEQ ISS
Mobile Biobehavioral measures ongoing data collection through continuous use of wearable sensors peripherals EMA and neural LFPs
End Month 12 Begin 1 month withdrawal period The DBS system will be turned off completely at some point during this gradual taper period The study doctor will make the clinical decision whether to restart stimulation
Repeat Assessments
Clinician-administered Vital Signs MADRS CGIS YMRS C-SSRS HAM-A MRTF PRISE
Subject Reported QIDS-SR QOLS SDS BIS ASRM PANAS MEQ ISS
Medical and Laboratory Testing Repeat MEG rsfMRI
Behavioral Tasks PRT and IMT at end-of-month 12 NeuroBehavioral Unit Will be in-situ staying locally during much of this time and spend one 24-hour period in the NBU
This will be NBU visit 8 of 8
Months 13-20 The team and subject will make the clinical decision whether to reinstate or deactive DBS following discontinuation phase
Repeat Assessments
Clinician-administered Vital Signs MADRS CGIS YMRS C-SSRS HAM-A MRTF PRISE
Subject Reported QIDS-SR QOLS SDS BIS ASRM PANAS MEQ ISS
Month 20 Last set of formal study visits All evaluations and labs will be repeated
Clinician-administered Vital Signs MADRS CGIS YMRS C-SSRS HAM-A MRTF PRISE
Subject Reported QIDS-SR QOLS SDS BIS ASRM PANAS MEQ ISS
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None