Closed-Loop Deep Brain Stimulation for Treatment-Resistant Bipolar Depression

NCT07127913 | Recruiting DMC FDA Device

• 1 other identifier: 17-23724B
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Change in Montgomery-Asberg Depression Rating Scale (MADRS) score

  Effect size comparing closed-loop stimulation, open-loop (fixed intermittent) stimulation, and sham stimulation (MADRS score before and after each treatment period of the crossover). Higher MADRS score indicates more severe depression; the overall score ranges from 0 to 60.

  Administered twice at baseline and every 2 weeks for the 36-40 weeks of Stage 3

Secondary Outcomes (2)

• Change in Hamilton Depression Rating Scale (HAMD-17) score

  Administered at baseline and every 4 weeks for the 36-40 weeks of Stage 3

• Change in the Inventory of Depressive Symptomatology Self-Report (IDS-SR) score

  Administered at baseline and every 4 weeks for the 36-40 weeks of Stage 3

Other Outcomes (6)

• Daily stimulation events

  Up to 24 weeks

• Stimulation duration

  Up to 24 weeks

• Stimulation site identification

  Decision made in the 1-3 months following Stage 1

Study Arms (3)

Experimental: Arm 1: Intervention (stimulation ON)

EXPERIMENTAL

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.

Device: Device: Stimulation-ON

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

SHAM COMPARATOR

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.

Device: Device: Stimulation-OFF

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

ACTIVE COMPARATOR

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.

Device: Device: Stimulation -ON Active Control

Interventions

Device: Stimulation-ON DEVICE

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

Experimental: Arm 1: Intervention (stimulation ON)

Device: Stimulation-OFF DEVICE

No neurostimulation from the NeuroPace RNS® System

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

Device: Stimulation -ON Active Control DEVICE

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

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

Eligibility Criteria

• Age: 22 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Andrew Krystal: lead

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

RECRUITING

MeSH Terms

Conditions

Bipolar Disorder; Depression

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Study Officials

• Andrew Krystal, MD, MS

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrew Krystal, MD, MS

CONTACT

510-621-3193; trdepression@ucsf.edu

Natalie Becker, BS

CONTACT

510-621-3193; trdepression@ucsf.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Psychiatry and Behavioral Sciences

Study Record Dates

• First Submitted: August 1, 2025
• First Posted: August 17, 2025
• Study Start: July 16, 2025
• Primary Completion (Estimated): June 28, 2030
• Study Completion (Estimated): June 28, 2035
• Last Updated: August 17, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)