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 subject's implanted device for the
duration of the participant's stay. A research coordinator will be responsible for
restarting streaming sessions every eight hours, ensuring the patient's 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 participant's 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 (e.g., 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 Severity/Change
(CGI-S/I), Young Mania Rating Scale (YMRS)56, 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, PT/PTT/INR, 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:
(e.g., 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 VC/VS 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-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 the neuropsych battery defined in
the screening/baseline 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
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 screening/baseline 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 screening/baseline 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.