Bipolar II DisorderPReSiDio-BPNCT07127913
Closed-Loop Deep Brain Stimulation for Treatment-Resistant Bipolar Depression
A study testing Device: Stimulation-ON and Device: Stimulation-OFF in people with Bipolar II Disorder and Bipolar II Disorder, Most Recent Episode Major Depressive, run by Andrew Krystal at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 22 to 70 years
- Conditions the study is for
- Bipolar II Disorder, Bipolar II Disorder, Most Recent Episode Major Depressive
- What is being tested?
- Device: Stimulation-ON and Device: Stimulation-OFF
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Jul 2025to 28 Jun 2035
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 22 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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
Show all 19Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of California, San Francisco
San Francisco, California, 94143
Andrew Krystal, MD, MS, 510-621-3193, trdepression@ucsf.edu
Natalie Becker, BS, 510-621-3193, trdepression@ucsf.edu
About this study
Official title: Closed-Loop Deep Brain Stimulation for Bipolar Depression (PReSiDio-BP)
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.
Read the detailed description
This is a single-center 3-stage feasibility study of personalized closed-loop stimulation for treatment resistant Bipolar Depression. Depending on participant's results at each stage, he/she might not be eligible to proceed to all 3 stages.
Stage 1 of the study will involve surgically implanting small, thin electrodes in brain regions that regulate depression in order to identify personalized treatment sites. The researchers will test stimulation in the different brain regions and their effect on bipolar depression symptoms. The electrodes will be surgically removed at the end of Stage 1.
Stage 2 will involve a second brain surgery to implant the NeuroPace RNS® System. Researchers will use information from Stage 1 to decide where to implant the electrodes of the RNS System. Over the next ~4-18 months, participants will have regular study visits in the clinic where the researchers will determine a personalized brain activity pattern that correlates with depression symptoms and can be paired with stimulation to improve depression symptoms.
Stage 3 will be 36-40 weeks long and will involve turning ON and OFF the intervention to test its effectiveness. Participants will have a variable start time for Stage 3 to facilitate blinding of both patients and clinician raters. This variable time will be randomized from conditions of 0 days, 2 weeks, or 4 weeks (during which time participants will remain on optimized closed-loop stimulation). Each participant will have three 12-week periods: closed-loop stimulation (intervention), open-loop/fixed intermittent stimulation (active control), and sham (passive control), order counterbalanced.
At the end of this stage the participant can choose to continue with long-term follow-up or have the RNS System surgically removed.
- Being tested
- Device: Stimulation-ON, Device: Stimulation-OFF, Device: Stimulation -ON Active Control
- Keywords
- Bipolar II Disorder, Depression, Treatment-resistance, Deep brain stimulation, Closed-loop, Biomarker, Responsive neurostimulation, Brain surgery
- Medical subject headings
- Bipolar Disorder, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Device: Stimulation-ONDevice
Active neurostimulation from the NeuroPace RNS® System triggered by a biomarker
Device: Stimulation-OFFDevice
No neurostimulation from the NeuroPace RNS® System
Device: Stimulation -ON Active ControlDevice
Active neurostimulation from the NeuroPace RNS® System triggered with a fixed duty cycle
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Device: Device: Stimulation -ON Active Control |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Effect size comparing closed-loop stimulation, open-loop (fixed intermittent) stimulation, and sham stimulation (HAMD-17 score before and after each treatment period of the crossover). The score for Hamilton Depression Rating Scale ranges from 0-50, with a higher score indicating more severe depression.
Measured: 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
Effect size comparing closed-loop stimulation, open-loop (fixed intermittent) stimulation, and sham stimulation (IDS-SR score before and after each treatment period of the crossover). The scores range from 0 to 27, with higher scores indicating more depressive symptoms.
Measured: Administered at baseline and every 4 weeks for the 36-40 weeks of Stage 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2025
- Study start16 Jul 2025
- Primary completion28 Jun 2030 (estimated)
- Study completion28 Jun 2035 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bipolar II DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Andrew Krystal
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Andrew Krystal, University of California, San Francisco
- Investigators
- Andrew Krystal, MD, MS, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07127913
- Sponsor's protocol ID
- 17-23724B
- Acronym
- PReSiDio-BP
- Status last verified
- Aug 2025
- First submitted
- 1 Aug 2025
- Last updated
- 17 Aug 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Closed-Loop Deep Brain Stimulation for Bipolar Depression (PReSiDio-BP)
- ClinicalTrials.gov ID
- NCT07127913
- Acronym / sponsor ID
- PReSiDio-BP / 17-23724B
- Keywords
- Bipolar II Disorder, Depression, Treatment-resistance, Deep brain stimulation, Closed-loop, Biomarker, Responsive neurostimulation, Brain surgery
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Andrew KrystalUniversity, hospital or other
- Study start
- 16 Jul 2025 (actual)
- Primary completion
- 28 Jun 2030 (estimated)
- Study completion
- 28 Jun 2035 (estimated)
- First posted
- 17 Aug 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a single-center 3-stage feasibility study of personalized closed-loop stimulation for treatment resistant Bipolar Depression. Depending on participant's results at each stage, he/she might not be eligible to proceed to all 3 stages.
Stage 1 of the study will involve surgically implanting small, thin electrodes in brain regions that regulate depression in order to identify personalized treatment sites. The researchers will test stimulation in the different brain regions and their effect on bipolar depression symptoms. The electrodes will be surgically removed at the end of Stage 1.
Stage 2 will involve a second brain surgery to implant the NeuroPace RNS® System. Researchers will use information from Stage 1 to decide where to implant the electrodes of the RNS System. Over the next ~4-18 months, participants will have regular study visits in the clinic where the researchers will determine a personalized brain activity pattern that correlates with depression symptoms and can be paired with stimulation to improve depression symptoms.
Stage 3 will be 36-40 weeks long and will involve turning ON and OFF the intervention to test its effectiveness. Participants will have a variable start time for Stage 3 to facilitate blinding of both patients and clinician raters. This variable time will be randomized from conditions of 0 days, 2 weeks, or 4 weeks (during which time participants will remain on optimized closed-loop stimulation). Each participant will have three 12-week periods: closed-loop stimulation (intervention), open-loop/fixed intermittent stimulation (active control), and sham (passive control), order counterbalanced.
At the end of this stage the participant can choose to continue with long-term follow-up or have the RNS System surgically removed.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Experimental: Arm 1: Intervention (stimulation ON) | Experimental | Device: Device: Stimulation-ONThis 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: Arm 2: Sham Control (stimulation OFF) | Sham comparator | Device: Device: Stimulation-OFFThis 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: Arm 3: Active Control (stimulation ON fixed intermittent) | Active comparator | Device: Device: Stimulation -ON Active ControlThis 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. |
Who may qualify
- Ages
- 22 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Device: Stimulation-ONActive neurostimulation from the NeuroPace RNS® System triggered by a biomarker | Device | Experimental: Arm 1: Intervention (stimulation ON) |
| Device: Stimulation-OFFNo neurostimulation from the NeuroPace RNS® System | Device | Sham Comparator: Arm 2: Sham Control (stimulation OFF) |
| Device: Stimulation -ON Active ControlActive neurostimulation from the NeuroPace RNS® System triggered with a fixed duty cycle | Device | Active Comparator: Arm 3: Active Control (stimulation ON fixed intermittent) |
Primary outcome
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
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.
2 secondary outcomes
Change in Hamilton Depression Rating Scale (HAMD-17) score
Time frame: 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
Time frame: Administered at baseline and every 4 weeks for the 36-40 weeks of Stage 3
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Andrew Krystal, MD, MS principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Device: Stimulation-ON and Device: Stimulation-OFF in people with Bipolar II Disorder and Bipolar II Disorder, Most Recent Episode Major Depressive, run by Andrew Krystal at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 17 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Andrew Krystal, MD, MS (510-621-3193, trdepression@ucsf.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2025.