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
|Condition or disease||Intervention/treatment||Phase|
|Treatment Resistant Depression||Device: Epidural Prefrontal Cortical Stimulation (EpCS)||Not Applicable|
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 :||Interventional (Clinical Trial)|
|Estimated Enrollment :||15 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Epidural Prefrontal Cortical Stimulation (EpCS) in Severe Treatment Resistant Depression|
|Estimated Study Start Date :||December 1, 2019|
|Estimated Primary Completion Date :||December 31, 2021|
|Estimated Study Completion Date :||December 31, 2021|
Experimental: Epidural Prefrontal Cortical Stimulation (EpCS)
Stereotactically implanted bilateral EpCS
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.
- 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.
- 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).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04124341
|Contact: Ziad Nahas, MD, MSCRfirstname.lastname@example.org|
|Contact: Maxwell Thorpeemail@example.com|