Actively Recruiting
Closed-Loop Deep Brain Stimulation for Bipolar Depression (PReSiDio-BP)
Led by Andrew Krystal · Updated on 2025-08-17
10
Participants Needed
1
Research Sites
260 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Neurons are specialized cells responsible for brain functions through electrical signals, which can be disrupted in major depression. This research investigates a personalized brain stimulation approach for bipolar depression, focusing on patients whose symptoms have not improved with current treatments. The study uses the NeuroPace Responsive Neurostimulation (RNS) System, approved for epilepsy, to assess its potential in improving bipolar depression by altering brain activity. The study has three stages. Stage 1 involves implanting thin electrodes in brain areas linked to depression to find personalized treatment targets, with electrodes removed afterward. Stage 2 includes implanting the NeuroPace RNS System based on Stage 1 findings; participants attend regular visits over 4 to 18 months to identify brain activity patterns associated with depression symptoms and pair them with stimulation. Stage 3 lasts 36 to 40 weeks, during which stimulation is turned on and off in randomized 12-week periods, including closed-loop stimulation, fixed intermittent stimulation, and sham control. Participants may continue with long-term follow-up or choose device removal after Stage 3. Participants will have multiple clinic visits for brain activity monitoring and depression assessments using scales like the Montgomery-Asberg Depression Rating Scale (MADRS), Hamilton Depression Rating Scale (HAMD-17), and Inventory of Depressive Symptomatology Self-Report (IDS-SR). The researchers track changes in depression symptoms during treatment periods and monitor safety throughout. The study spans from initial surgery through treatment and follow-up phases, ending in 2035, with careful evaluation of personalized brain stimulation effects on bipolar depression.
CONDITIONS
Brief Title
Closed-Loop Deep Brain Stimulation for Treatment-Resistant Bipolar Depression
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Age between 22 and 70 years
- Diagnosed with Bipolar II Disorder with a depressive episode lasting at least 1 year that is treatment resistant
- No manic or hypomanic episode in the last 2 years
- Taking a mood stabilizer (lithium >0.6 mEq/L or valproate >350 mM/L), an atypical antipsychotic, or both at stable dose for at least 2 weeks before the study
- Failed, unable to complete, or unwilling to receive electroconvulsive therapy (ECT)
- Montgomery-Asberg Depression Rating Scale (MADRS) score greater than 26 at two baseline visits
- Able to complete repeated depression rating scales
- No expected changes in psychotropic medication regimen during the 4 weeks before and during the study
- Willing and able to undergo invasive brain recording and stimulation
- Willing and able to attend multiple research visits and perform at-home research activities
- Able to provide informed consent
- Able to speak and read English
You will not qualify if you...
- Diagnosis of psychotic disorder, eating disorder, panic disorder, PTSD, OCD, tic disorder, or other psychiatric disorders except MDD or generalized anxiety disorder
- Generalized anxiety disorder is the main current disorder
- Active suicidal thoughts with intent and plan
- Suicide attempt requiring hospitalization in past 2 years
- Alcohol or substance abuse or dependence in past 6 months (except caffeine)
- Personality disorder that may affect compliance or safety
- Fibromyalgia or chronic fatigue syndrome
- Current need for chronic narcotic use
- History of traumatic brain injury, neurological disorder, or developmental delay
- History of seizures
- MRI abnormalities within past year
- Previous brain surgery involving ablation or stimulation devices
- Implantable hardware incompatible with MRI or study
- Major medical conditions increasing surgery risk (severe diabetes, organ failure, recent stroke, unstable cardiovascular disease, infection, malignancy with less than 5 years life expectancy)
- Inability to stop blood thinning medications safely
- Coagulopathy unless cleared by hematology
- Allergies to materials in NeuroPace RNS System
- Living alone without caregiver support after hospital stay
- Inability to comply with study follow-up visits
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 screening and enrollment visit
Duration - Duration of initial surgical implantation and removal period
Participants undergo brain surgery to implant electrodes to identify personalized treatment sites, followed by electrode removal at the end of this stage.
Surgical procedure and hospital stay
Duration - Approximately 4 to 18 months
Participants undergo a second brain surgery to implant the NeuroPace RNS® System and receive personalized closed-loop stimulation with regular clinic visits to optimize brain activity patterns correlated with depression symptoms.
Regular study visits in the clinic during this period
Duration - 36 to 40 weeks
Participants complete three 12-week treatment periods in random order: closed-loop stimulation (intervention), fixed intermittent stimulation (active control), and no stimulation (sham control). Each period tests the effectiveness of different stimulation settings with a variable start time to maintain blinding.
Clinic visits every 2 to 4 weeks for depression rating assessments
Duration - Variable based on participant choice
After treatment, participants may choose to continue long-term follow-up or have the NeuroPace RNS® System surgically removed.
Visits as needed for follow-up or removal surgery
Trial Site Locations
Total: 1 location
1
University of California, San Francisco
San Francisco, California, United States, 94143
Actively Recruiting
Research Team
A
Andrew Krystal, MD, MS
N
Natalie Becker, BS
How is the study designed?
Study Type
INTERVENTIONAL
Masking
TRIPLE
Allocation
RANDOMIZED
Model
CROSSOVER
Primary Purpose
TREATMENT
Number of Arms
3
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