Recruiting

Closed-Loop DBS

Sponsor:

Andrew Krystal

Code:

NCT04004169

Conditions

Major Depressive Disorder

Eligibility Criteria

Sex: All

Age: 22 - 70

Healthy Volunteers: Not accepted

Interventions

Stimulation-ON

Stimulation-OFF

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 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 depression.

Conditions

Major Depressive Disorder

Study ID

NCT04004169

Start date

Jul 18, 2019

Status verified date

Jul, 2026

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 the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) diagnostic criteria for Major Depressive Disorder (MDD) without psychosis based on a Structured Clinical Interview for DSM-V (SCID) with current episode ≥ 2 years that is treatment- resistant (4 adequate trials (including ECT), 3 classes of medications, one augmentation strategy, psychotherapy) as measured by the antidepressant treatment history form (ATHF).
  • Failed electroconvulsive therapy (ECT) due to inability to achieve sustained response (2 failed attempts to discontinue ECT treatment) or discontinued due to intolerable side effects.
  • Has MADRS score of > 26 at both baseline and screening visit
  • The presence of variability on repeated administrations of MDD rating scales (minimum of 2-point variation on the HAMD-6 administered 3 times a day for 3 days), which is required for the identification of a neural biomarker.
  • If patient is on a regimen of psychotropic medication, no changes in this regimen should be made 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, bipolar 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
  • Women who are pregnant, plan to become pregnant, or breast feeding
  • Inability to speak and/or read English
  • Inability to give consent
  • Significant cognitive impairment or dementia (MoCA < 25)
  • Likely to require ECT during the course of the study

Study Design

Enrollment

12 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm 1: Intervention (stimulation ON)

This is a crossover trial. Each patient will receive 6 wks of stimulation ON (arm 1), stimulation OFF (arm 2), and Stimulation ON Active Control (sham biomarker) (arm 3) in random order. After 6 months of intervening therapy, this 3-period crossover study will be repeated.

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

This is a crossover trial. Each patient will receive 6 wks of stimulation ON (arm 1), stimulation OFF (arm 2), and Stimulation ON Active Control (sham biomarker) (arm 3) in random order. After 6 months of intervening therapy, this 3-period crossover study will be repeated.

active comparator: Arm 3: Active Control (stimulation ON triggered by sham biomarker)

This is a crossover trial. Each patient will receive 6 wks of stimulation ON (arm 1), stimulation OFF (arm 2), and stimulation ON Active Control (sham biomarker) (arm 3) in random order. After 6 months of intervening therapy, this 3-period crossover study will be repeated.

Interventions

Stimulation-ON

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

Stimulation-OFF

No neurostimulation from the NeuroPace RNS® System

Stimulation-ON Active Control

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

Primary outcome measure

  • change in MADRS score [ Time Frame: administered at baseline and every 2 weeks for the first 18 weeks of stage 3 ]

Central Contacts and Locations

Central contacts

Katherine Scangos, MD, PhD

415-476-7439trdepression@ucsf.edu

Rebecca Martinez, MS

415-476-7439rebecca.martinez@ucsf.edu

Locations

University of California, San Francisco

Recruiting

San Francisco, California, United States, 94143

Contacts

Katherine Scangos, MD, PhD

415- 476-7439trdepression@ucsf.edu

Rebecca Martinez, MS

415- 476-7439rebecca.martinez@ucsf.edu

Principal Investigator:

Katherine Scangos, MD, PhD

More Information

Sponsor

Andrew Krystal

Last update posted

Aug 3, 2026

Last verified

Jul, 2026

Keywords

  • Major Depressive 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 2026-08-03.