Deep Brain Stimulation for Bipolar Depression

(PReSiDio-BP Trial)

Overseen By Natalie Becker, BS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Andrew Krystal

Must be taking: Mood stabilizers, atypical antipsychotics

Must not be taking: Chronic narcotics

Disqualifiers: Psychotic disorder, substance abuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for bipolar depression using a device that sends small electrical signals to the brain. The goal is to determine if this personalized brain stimulation, known as Closed-Loop Deep Brain Stimulation, can reduce symptoms in individuals whose depression hasn't improved with other treatments. Participants will have the device implanted to monitor and adjust their brain activity. The trial seeks individuals with bipolar depression who have struggled with symptoms for at least a year despite trying other therapies.

As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could lead to new treatment options for bipolar depression.

Will I have to stop taking my current medications?

You will need to continue taking your current mood stabilizer or antipsychotic medication throughout the study unless it's necessary to stop for safety reasons. If you're on a stable regimen of psychotropic medication, no changes should be expected during the 4 weeks before and throughout the study.

What prior data suggests that the NeuroPace Responsive Neurostimulation (RNS) System is safe for treating bipolar depression?

Studies have shown that deep brain stimulation (DBS) can safely treat various conditions. For example, DBS has helped people with obsessive-compulsive disorder (OCD) when other treatments failed. In another study, researchers tested DBS on patients with difficult-to-treat depression, and about 66% showed improvement after six months.

The device used in the current trial, the NeuroPace Responsive Neurostimulation (RNS) System, has already received FDA approval for treating epilepsy, indicating it has been tested for safety in people with that condition. While researchers continue to study DBS for bipolar depression, earlier findings suggest it might be well-tolerated. Each person's experience can differ, so discussing any concerns with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about closed-loop deep brain stimulation for bipolar depression because it offers a unique approach compared to current treatments like mood stabilizers and antidepressants. Unlike these medications, which often take weeks to show effects and can have significant side effects, closed-loop deep brain stimulation uses targeted electrical impulses to regulate brain activity in real-time. This method has the potential to provide more immediate relief from symptoms and can be adjusted to the patient's needs, offering a personalized treatment experience. By directly modulating brain circuits involved in mood regulation, this technique could revolutionize how we manage bipolar depression.

What evidence suggests that the NeuroPace RNS System could be effective for treating bipolar depression?

Research shows that deep brain stimulation (DBS) could help treat severe depression cases. Studies have found that DBS benefits 60% of people who haven't improved with other treatments. In some studies, patients experienced a 43% decrease in depression symptoms 12 months after the device activation. By 24 months, this decrease improved to 53%. This trial will evaluate different stimulation settings, including continuous stimulation, sham control, and fixed intermittent stimulation, to determine the most effective approach. The study's personalized approach aims to adjust the treatment to fit each person's unique brain activity. ^{2 5 6 7 8}

Who Is on the Research Team?

Andrew Krystal, MD, MS

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for individuals with treatment-resistant bipolar depression. Participants must have a history of inadequate response to standard therapies. The study involves those who are eligible for brain surgery to implant a device that will deliver electrical impulses.

Inclusion Criteria

Ability to speak and read English

Willing and able to provide informed consent

I have been on mood stabilizers or antipsychotics for at least 2 weeks.

Exclusion Criteria

Major medical co-morbidities

I have had brain surgery or a brain stimulation device implanted.

I have a blood clotting disorder.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Stage 1: Electrode Implantation and Testing

Surgical implantation of electrodes to identify personalized treatment sites and test stimulation effects on bipolar depression symptoms. Electrodes are removed at the end of this stage.

1-3 months

Stage 2: NeuroPace RNS System Implantation

Second brain surgery to implant the NeuroPace RNS System. Regular clinic visits to determine personalized brain activity patterns for stimulation.

4-18 months

Stage 3: Crossover Trial

36-40 weeks of testing the effectiveness of closed-loop stimulation with variable start times and three 12-week periods: closed-loop stimulation, open-loop/fixed intermittent stimulation, and sham.

36-40 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment. Option to continue with long-term follow-up or have the RNS System removed.

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Closed-Loop Deep Brain Stimulation

Trial Overview The trial tests the NeuroPace Responsive Neurostimulation (RNS) System, which is FDA approved for epilepsy but now being studied for bipolar depression. It measures and alters brain activity via electrical stimulation to see if it can reduce depressive symptoms.

How Is the Trial Designed?

Group I: Experimental: Arm 1: Intervention (stimulation ON) Experimental Treatment 1 Intervention

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.

Group II: Active Comparator: Arm 3: Active Control (stimulation ON fixed intermittent) Active Control 1 Intervention

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.

Group III: Sham Comparator: Arm 2: Sham Control (stimulation OFF) Placebo Group 1 Intervention

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.

Who Is Running the Clinical Trial?

Andrew Krystal

Lead Sponsor

Trials

2

Recruited

10+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06599099

Study Details | NCT06599099 | Deep Brain Stimulation of ... This research study is to investigate the use of technology called Deep Brain Stimulation (DBS) to potentially improve Treatment-Resistant Bipolar Depression ( ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9587188/

Deep Brain Stimulation for Depression - PMC - PubMed Central DBS across different targets is associated with on average 60% response rates in previously refractory chronically depressed patients. However, ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X25003109

Revisiting subcallosal cingulate deep brain stimulation for ... Average MADRS reduction was 43 % at 12 months and 53 % at 24 months post-device activation, with response rates of 46 % and 55 %, and partial response rates of ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11219029/

Closed-loop neuromodulation in an individual with ... Deep brain stimulation is a promising treatment for neuropsychiatric conditions such as major depression.

5. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT07127913

Closed-Loop Deep Brain Stimulation for Treatment ... 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 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10188203/

Closed Loop Deep Brain Stimulation for Psychiatric Disorders DBS has strong open-label evidence in OCD, with multiple groups reporting 60-70% response rates in otherwise treatment-refractory cases, across a variety of ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1878747923010784

Deep Brain Stimulation for Depression The first open-label trial of DBS for TRD conducted by Mayberg et al. demonstrated its safety and efficacy, with a response rate (RS) at 6 months of 66% and ...

8. tandfonline.com tandfonline.com/doi/full/10.1080/14737175.2025.2562119?src=

How impactful is deep brain stimulation for depression? The robust and sustained clinical effects of DBS in multiple open-label trials highlight the potential impact of DBS for long-term depression treatment. The ...