Closed-Loop Deep Brain Stimulation for Major Depression
This study is testing a personalized brain stimulation approach for major depression. It uses a surgically implanted device, the NeuroPace RNS® System, to measure your brain activity and deliver small electrical impulses to help reduce depression symptoms. You might be able to join if you are 22-70 years old and have major depressive disorder that hasn't improved with other treatments. The study will look at how much your depression symptoms improve, measured by a score called MADRS, over 18 weeks in one stage of the study. The current status of this study is unclear, and it plans to enroll 12 participants.
- Study design
- This is a single-center study with 12 participants, divided into three stages. It is an interventional study, meaning participants will receive a specific treatment.
- What's involved
- You would undergo two brain surgeries to implant and then replace electrodes. You would also have regular clinic visits for about 4-12 months, followed by a 12-month period where the stimulation is turned on and off.
- Compensation
- Not stated in the trial record.
- Follow-up
- Your depression symptoms will be measured every two weeks for the first 18 weeks of Stage 3.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT04004169
Closed-Loop Deep Brain Stimulation for Major Depression
Recruiting
NAAges 22–70InterventionalTreatmentAndrew KrystalInvestigator-initiated
~12 participants
Updated 2026-08-03 on ClinicalTrials.gov
What's tested:Stimulation-ONStimulation-OFFStimulation-ON Active Control
At a glance
Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
change in MADRS score
Measured over administered at baseline and every 2 weeks for the first 18 weeks of stage 3
Conditions
Where it's being run
1 sites across 1 statesCalifornia1
Study leadership
- Andrew Krystal, MD, MS · PRINCIPAL_INVESTIGATOR · University of California, San Francisco
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
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
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
What this trial measures
- change in MADRS scoreadministered at baseline and every 2 weeks for the first 18 weeks of stage 3
Effect size of active compared to sham stimulation (mean difference in Montgomery Asberg Depression Rating Scale (MADRS) score before and after the sham and treatment periods). Higher MADRS score indicates more severe depression; the overall score ranges from 0 to 60.