Personalized closed-loop deep brain stimulation for treatment-resistant Bipolar II depression

Closed-Loop Deep Brain Stimulation for Bipolar Depression (PReSiDio-BP)

This study will test a personalized closed-loop deep brain stimulation system to try to reduce depressive symptoms in adults with treatment-resistant Bipolar II disorder.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 22 Years to 70 Years
• Sex: All
• Sponsor: University of California, San Francisco (other)
• Locations: 1 site (San Francisco, California)
• Trial ID: NCT07127913 on ClinicalTrials.gov

What this trial studies

This single-center, three-stage feasibility protocol uses temporary implanted electrodes to map brain sites tied to each participant's depression, followed by implantation of the NeuroPace RNS® System to record brain activity and deliver responsive stimulation. Stage 1 implants exploratory electrodes briefly to identify individualized stimulation targets and then removes them. Stage 2 places the RNS system based on Stage 1 findings and records over months to define a brain-activity pattern linked to symptoms that can trigger stimulation. Stage 3 uses randomized, variable start ON/OFF periods over roughly 36–40 weeks to test whether the personalized closed-loop stimulation reduces depressive symptoms compared with OFF periods while maintaining blinding for participants and raters.

Who should consider this trial

Good fit: Adults aged 22–70 with Bipolar II disorder in a depressive episode lasting at least one year who have not responded to multiple therapies (including failed or intolerant-to-ECT cases) and who can remain on required mood-stabilizing medication are primary candidates.

Not a fit: People without treatment-resistant Bipolar II depression, those with a manic or hypomanic episode within the prior two years, or anyone unable or unwilling to undergo neurosurgery and frequent in-person follow-up are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, this approach could offer a personalized neuromodulation option that meaningfully reduces depressive episodes in people with treatment-resistant Bipolar II disorder.

How similar studies have performed: Responsive neurostimulation is an approved therapy for epilepsy and closed-loop stimulation has shown promising results in small open-label studies for major depression, but closed-loop DBS specifically for treatment-resistant Bipolar II depression remains largely experimental.

Eligibility criteria

Inclusion Criteria:

* Age 22-70
* Meet Diagnostic and Statistical Manual-V (DSM-V) diagnostic criteria for Bipolar II Disorder, with an episode of depression lasting at least 1 year that is treatment resistant as defined above, without a manic or hypomanic episode in the last 2 years; patients must be taking a mood stabilizer (lithium \>0.6 mEq/L or valproate \>350 mM/L), an atypical antipsychotic, or a combination of a mood stabilizer and an atypical antipsychotic for at least 2 weeks at a stable dosage before starting the study and must continue taking anti-manic medication throughout their participation in the study unless discontinuation is necessary because of patient safety/health considerations.
* Must have either failed ECT (it was effective but not tolerated due to side effects; it was effective, but patients could not achieve a sustained response), not been able to complete a course of ECT due to side effects, or have been medically advised to receive ECT and have been unwilling or unable to obtain ECT.
* Has MADRS score of \> 26 at two baseline visits
* Ability to complete repeated administrations of MDD rating scales.
* If patient is on a regimen of psychotropic medication, no changes in this regimen should be expected during the 4 weeks prior to entry into and the duration of the study.
* Willing and able to undergo invasive brain recording/stimulation study
* Willing and able to attend multiple research visits and perform at-home research protocol
* Willing and able to provide informed consent
* Ability to speak and read English

Exclusion Criteria:

* Meets DSM-V criteria for a psychotic disorder, eating disorder, panic disorder, posttraumatic stress disorder, obsessive compulsive disorder, tic disorder, or another comorbid psychiatric disorder other than MDD or generalized anxiety disorder based on a SCID
* Generalized anxiety disorder is the primary DSM-V disorder during the current MDD episode
* Active suicidal ideation with intent and plan as defined by a score of 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS)
* History of suicide attempt requiring hospitalization in previous 2 years.
* Meets criteria for alcohol or substance abuse or dependence (other than caffeine) in previous 6 months, determined by the SCID
* Has a personality disorder based on the investigator's assessment that the investigator believes will adversely impact subject compliance or safety
* Fibromyalgia or chronic fatigue syndrome
* Current condition requiring chronic narcotic use
* History of traumatic brain injury, another neurological disorder, or developmental delay
* History of seizures
* MRI (done within one year of the first visit) with significant abnormalities
* Previous ablative intracranial surgery or previously implanted deep brain stimulation system or any previously implanted device treatment involving brain stimulation
* Implantable hardware not compatible with MRI or with the study
* Major medical co-morbidities increasing the risk of surgery including severe diabetes, major organ system failure, history of hemorrhagic stroke, need for chronic anticoagulation other than aspirin, active infection, intracranial space occupying lesion, increased intracranial pressure, cardiovascular accident within the last month, aneurysm/abnormality, retinal detachment, unstable cardiovascular disease (recent myocardial infarction, severe ischemia, severe or uncontrolled hypertension), immunocompromised state, or malignancy with \< 5 years life expectancy
* Inability to stop Coumadin or platelet anti-aggregation therapy for surgery and after surgery. - Patients taking these medications will need to discuss the need/risk of continuing these medications with their physicians and the PI or study personnel may contact the treating physician(s) to discuss the risks of anticoagulation/antiaggregation therapy discontinuation
* Coagulopathy. Patients will be excluded unless assessed and cleared by hematology
* Allergies or known hypersensitivity to materials in the NeuroPace RNS® System (i.e. titanium, polyurethane, silicone, polyetherimide, stainless steel)
* Subject lives alone without possibility of caregiver support post-hospital stay
* Inability to comply with study follow-up visits

Where this trial is running

San Francisco, California

• University of California, San Francisco — San Francisco, California, United States (RECRUITING)

Study contacts

• Principal investigator: Andrew Krystal, MD, MS — University of California, San Francisco
• Study coordinator: Andrew Krystal, MD, MS

Conditions: Bipolar II Disorder, Bipolar II Disorder, Most Recent Episode Major Depressive, Depression, Treatment-resistance, Deep brain stimulation, Closed-loop, Biomarker, Responsive neurostimulation