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EpCS in Severe Treatment Resistant Depression

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ClinicalTrials.gov Identifier: NCT04124341
Recruitment Status : Not yet recruiting
First Posted : October 11, 2019
Last Update Posted : October 30, 2019
Sponsor:
Information provided by (Responsible Party):
University of Minnesota

Tracking Information
First Submitted Date  ICMJE October 10, 2019
First Posted Date  ICMJE October 11, 2019
Last Update Posted Date October 30, 2019
Estimated Study Start Date  ICMJE December 1, 2019
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 10, 2019)
Change in LPP Amplitude [ Time Frame: 6 months ]
Change in late positive potential (LPP) amplitude as a result of Bayesian optimized bilateral EpCS. LPP is an event-related potential (ERP) measured by electroencephalography (EEG), which reliably captures biased attention and early affective responses to environmental stimuli.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT04124341 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 10, 2019)
Change in HRSD Scores [ Time Frame: 6 months ]
In order to demonstrate that sustained lowering of LPP, as a result of Bayesian optimized bilateral EpCS, change in Hamilton Rating Scale for Depression (HRSD) scores will be calculated. HDRS is a 24-item interview-based tool measuring depression symptoms in the previous week. Scoring is based on only the first 17 items. Eight items are scored on a 5-point scale, ranging from 0 = not present to 4 = severe. Nine are scored from 0-2. Total scores are the sum of the 17 item scores and range from 0 (Normal functioning) to 22 (severe depression).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE EpCS in Severe Treatment Resistant Depression
Official Title  ICMJE Epidural Prefrontal Cortical Stimulation (EpCS) in Severe Treatment Resistant Depression
Brief Summary Purpose: Treatment-resistant depression (TRD) is a leading cause of premature mortality and healthcare costs. Negative stimuli capture the attention of depressed patients. The more entrenched these core attentional processes are, the longer patients remain ill. The parietal Late Positive Potential (LPP) [an event-related potential (ERP) measured by electroencephalography (EEG)], reliably captures biased attention and early affective responses to environmental stimuli. LPP is top-down modulated by the prefrontal cortex (PFC), an important target for depression treatment. Using a combination of anatomical, functional and electric-field simulation localization methods, the investigators will stereotactically implant 15 TRD patients with bilateral EpCS in a 2-phase approach. The investigators will confirm target engagement, reduction of LPP response, as well as examine the relationship between reductions in LPP and changes in depressive symptoms in TRD patients.
Detailed Description

Significance of Research Question: TRD patients present with the inability to disengage from negative perceptions and memories, which further dysregulates their mood and prevents them from engaging the outside world with flexibility. The investigators will demonstrate that LPP, a measure of early emotional processes, is a valid target for treating TRD. Intermittent bilateral EpCS will directly engage attention allocation networks, modulate LPP and decrease depressive symptoms. Using Bayesian optimization tools, the investigators can explore a larger number of settings than otherwise possible using classic parametric permutations, and reliably establish a sustained effective target engagement over time. Machine learning and an adaptive clinical trial design will offset the relatively small sample size, enable individualized treatments and help demonstrate that intermittent bilateral EpCS is an effective antidepressant treatment option for severe and chronic depression.

Objectives (confirm target engagement and demonstrate clinical relevance): To examine the relationship between reductions in LPP and clinical improvement. The investigators will define the optimal interval for adjusting EpCS settings over time and key design elements for a more definitive randomized control trial (RCT). This study also aims to explore other electrophysiology and behavioral measures that can add to the adaptive stimulation parameters adjustments method.

Hypothesis: Severe TRD patients with chronic intermittent EpCS therapy will show a sustained lowering of LPP (replication of target engagement) over a 6-month period, and this change will be related to decreases in Hamilton Rating Scale for Depression (HRSD24). This pattern will demonstrate that target engagement (lowering of LPP) is a key mechanism of antidepressant treatment with EpCS.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Treatment Resistant Depression
Intervention  ICMJE Device: Epidural Prefrontal Cortical Stimulation (EpCS)
Prior to surgery, subjects will undergo a high resolution structural scan to identify anatomical landmarks for rostral anterior and lateral prefrontal cortex. Following identification of target areas, EpCS quad leads will be projected over the anterior and lateral prefrontal cortex.Subjects will be kept in the hospital for a minimum of 72 hours for observation during which the investigators will obtain a high resolution spiral CT scan without contrast to confirm lead placements post- operatively and rule out any intra-cranial bleeds. Patients will receive analgesics which they may continue as an outpatient on as needed basis. During this 2-3 weeks recovery period, the attention to pain control and mood is critical. The research team will contact patients at least twice per week to check on their status.
Study Arms  ICMJE Experimental: Epidural Prefrontal Cortical Stimulation (EpCS)
Stereotactically implanted bilateral EpCS
Intervention: Device: Epidural Prefrontal Cortical Stimulation (EpCS)
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 Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: October 10, 2019)
15
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2021
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Participant has a diagnosis of chronic (greater than or equal to 2 years) depressive episode as defined by DSM V criteria
  • Participant has not had an adequate response to three or more adequate antidepressant treatments from at least two different antidepressant treatment categories in the current depressive episode according to the Antidepressant Treatment History Form (ATHF)
  • Participant must have had ECT or refused to undergo ECT if clinically indicated to them
  • Participant must have HRSD greater than or equal to 20
  • Participant must be able to complete the evaluations needed for this study including the functional imaging scans and the EEG Bayesian optimization sessions

Exclusion Criteria:

  • The EpCS would (in the investigator's judgment) pose an unacceptable surgical or medical risk for the participant
  • Participant is expected to require full body magnetic resonance imaging (MRI) during the clinical study
  • Participant is judged by the investigator to be acutely suicidal (e.g. within the 30 days prior to the EpCS implant the participant has made a suicide attempt or gesture or has made specific plans or preparation to commit suicide or scores 14 or higher on the SSI)
  • In addition to the acute suicidal risks mentioned above, participant meets any of the following:

    1. Has made a suicide attempt within the previous 12 months that required medical treatment
    2. Has made greater than or equal to two suicide attempts in the past 12 months
    3. Has a clear-cut plan for suicide that states that she/he cannot guarantee that she/he will call her/his regular psychiatrist or the Investigator if the impulse to implement the plan becomes substantial during the study
    4. Is likely to attempt suicide within the next six months, in the Investigator's opinion
  • Participant has a history of schizophrenia, schizoaffective disorder, or other psychotic disorder, or a current major depressive episode that includes psychotic features (commonly referred to as psychotic depression) according to the DSM V criteria
  • Participant with a diagnosis of dementia with a Mini-Mental State Exam (MMSE) less than or equal to 23
  • Female participant with a positive urine pregnancy test
  • Participant with a positive urine drug screen
  • Participant with DBS
  • Participant with VNS if the device was active in the last 6 months prior to study enrollment
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Ziad Nahas, MD, MSCR 612-273-9732 znahas@umn.edu
Contact: Maxwell Thorpe thorp131@umn.edu
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04124341
Other Study ID Numbers  ICMJE STUDY00006945
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: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University of Minnesota
Study Sponsor  ICMJE University of Minnesota
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account University of Minnesota
Verification Date October 2019

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