Recruiting

Personalized Stimulation

Sponsor:

Andrew Krystal

Code:

NCT07127913

Conditions

Bipolar II Disorder

Bipolar II Disorder, Most Recent Episode Major Depressive

Eligibility Criteria

Sex: All

Age: 22 - 70

Healthy Volunteers: Not accepted

Interventions

Device: Stimulation-ON

Device: Stimulation-OFF

Device: Stimulation -ON Active Control

Study Details

Brief summary:

Neurons are specialized types of cells that are responsible for carrying out the functions of the brain. Neurons communicate with electrical signals. In diseases such as major depression this electrical communication can go awry. One way to change brain function is using electrical stimulation to help alter the communication between groups of neurons in the brain.

The purpose of this study is to test a personalized approach to brain stimulation as an intervention for bipolar depression The study researchers will use a surgically implanted device to measure each individual's brain activity related to his/her depression. The researchers will then use small electrical impulses to alter that brain activity and measure whether these changes help reduce depression symptoms. This study is intended for patients with major depression whose symptoms have not been adequately treated with currently available therapies.

The device used in this study is called the NeuroPace Responsive Neurostimulation (RNS) System. It is currently FDA approved to treat patients with epilepsy. The study will test whether personalized responsive neurostimulation can safely and effectively treat bipolar depression.

Conditions

Bipolar II Disorder

Bipolar II Disorder, Most Recent Episode Major Depressive

Study ID

NCT07127913

Start date

Jul 16, 2025

Status verified date

Aug, 2025

Completion date

Jun 28, 2035

Anticipated

Primary completion date

Jun 28, 2030

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 22 - 70

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

10 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Experimental: Arm 1: Intervention (stimulation ON)

This is a crossover trial. Each patient will receive 12 wks of stimulation ON (arm 1), stimulation OFF (arm 2), and Stimulation ON Active Control (fixed intermittent) (arm 3) in random order.

sham comparator: Sham Comparator: Arm 2: Sham Control (stimulation OFF)

This is a crossover trial. Each patient will receive 12 wks of stimulation ON (arm 1), stimulation OFF (arm 2), and Stimulation ON Active Control (fixed intermittent) (arm 3) in random order.

active comparator: Active Comparator: Arm 3: Active Control (stimulation ON fixed intermittent)

This is a crossover trial. Each patient will receive 12 wks of stimulation ON (arm 1), stimulation OFF (arm 2), and Stimulation ON Active Control (fixed intermittent) (arm 3) in random order.

Interventions

Device: Stimulation-ON

Active neurostimulation from the NeuroPace RNS® System triggered by a biomarker

Device: Stimulation-OFF

No neurostimulation from the NeuroPace RNS® System

Device: Stimulation -ON Active Control

Active neurostimulation from the NeuroPace RNS® System triggered with a fixed duty cycle

Primary outcome measure

  • Change in Montgomery-Asberg Depression Rating Scale (MADRS) score [ Time Frame: Administered twice at baseline and every 2 weeks for the 36-40 weeks of Stage 3 ]

Central Contacts and Locations

Central contacts

Andrew Krystal, MD, MS

510-621-3193trdepression@ucsf.edu

Natalie Becker, BS

510-621-3193trdepression@ucsf.edu

Locations

University of California, San Francisco

Recruiting

San Francisco, California, United States, 94143

Contacts

Andrew Krystal, MD, MS

510-621-3193trdepression@ucsf.edu

Natalie Becker, BS

510-621-3193trdepression@ucsf.edu

Principal Investigator:

Andrew Krystal, MD, MS

More Information

Sponsor

Andrew Krystal

Last update posted

Aug 17, 2025

Last verified

Aug, 2025

Keywords

  • Bipolar II Disorder
  • Depression
  • Treatment-resistance
  • Deep brain stimulation
  • Closed-loop
  • Biomarker
  • Responsive neurostimulation
  • Brain surgery

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Andrew Krystal on 2025-08-17.