Deep Brain Stimulation for Depression

(PReSiDio Trial)

Overseen By Rebecca Martinez, MS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of California, San Francisco

Must not be taking: Narcotics, Anticoagulants

Disqualifiers: Psychotic disorder, Substance abuse, Seizures, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for major depression using the NeuroPace Responsive Neurostimulation (RNS) System, which sends tiny electrical impulses to the brain. The goal is to determine if these impulses can alter brain activity and reduce depression symptoms. It targets individuals whose depression hasn't improved with standard treatments like medication or therapy. Participants must have experienced depression for at least two years without relief from typical treatments. As an unphased trial, this study provides a unique opportunity to explore innovative treatment options for those unsuccessful with conventional methods.

Do I have to stop taking my current medications for the trial?

No, you don't have to stop taking your current medications. If you're on a regimen of psychotropic medication, you should not make any changes to it during the 4 weeks before entering the study and throughout its duration.

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

Research has shown that the NeuroPace Responsive Neurostimulation (RNS) System is safe. It has treated epilepsy for many years without major issues. A study with nine years of data found that most patients did not experience serious problems with it.

While the RNS System is new for treating depression, its use in epilepsy provides some confidence in its safety. The device helps by adjusting brain signals to reduce symptoms. So far, reports have not shown major safety concerns, suggesting it could be a safe option for those considering joining this trial for depression. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the NeuroPace Responsive Neurostimulation (RNS) System for depression because it offers a novel approach to treating this challenging condition. Unlike standard treatments, which often include medications like SSRIs and psychotherapy, the RNS System uses deep brain stimulation to deliver electrical impulses directly to specific brain areas involved in mood regulation. This method allows for real-time, personalized adjustments based on brain activity, potentially leading to more immediate and effective relief from depressive symptoms. Additionally, the RNS System's ability to adapt to a patient's unique brain patterns sets it apart from more static treatment options, making it a promising alternative for those who haven't responded to traditional therapies.

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

Research shows that the NeuroPace Responsive Neurostimulation (RNS) System can change brain activity. The FDA has already approved it for treating epilepsy, where it reduces seizures by sending small electrical signals to the brain. In this trial, participants will experience different stimulation settings: stimulation ON, stimulation OFF, and an active control with stimulation ON triggered by a sham biomarker. For depression, the approach mirrors its use in epilepsy. The device might alter brain cell communication, potentially reducing depression symptoms. Early results suggest this personalized method could be effective, especially for those whose depression hasn't improved with other treatments. ^{2 3 4 5 6}

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 adults aged 22-70 with major depression that hasn't improved after trying multiple treatments, including medication, psychotherapy, and ECT. Participants must have a consistent history of depression symptoms and not be planning any changes to their current medication regimen during the study. They should be able to attend research visits, perform at-home protocols, speak English, and provide informed consent.

Inclusion Criteria

Willing and able to attend multiple research visits and perform at-home research protocol

I am willing and able to participate in a study involving brain recording/stimulation.

Has MADRS score of > 26 at both baseline and screening visit

Exclusion Criteria

MRI (done within one year of the first visit) with significant abnormalities

Has a personality disorder based on the investigator's assessment that the investigator believes will adversely impact subject compliance or safety

Active suicidal ideation with intent and plan as defined by a score of 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS)

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 depression symptoms. Electrodes are removed at the end of this stage.

3-6 months

Stage 2: NeuroPace RNS System Implantation

Implantation of the NeuroPace RNS System and identification of personalized brain activity patterns correlated with depression symptoms over 4-12 months.

4-12 months

Stage 3: Intervention Testing

Testing the effectiveness of the intervention with ON and OFF periods over 12 months, including two 6-week periods with no stimulation.

12 months

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.

up to 1 year

What Are the Treatments Tested in This Trial?

Interventions

• NeuroPace Responsive Neurostimulation (RNS) System

Trial Overview The trial is testing a personalized brain stimulation device called NeuroPace RNS System—approved for epilepsy—to see if it can safely treat major depression. It involves surgically implanting the device to measure brain activity related to depression and using electrical impulses to potentially alter this activity.

How Is the Trial Designed?

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

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.

Group II: Arm 3: Active Control (stimulation ON triggered by sham biomarker) Active Control 1 Intervention

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.

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

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.

NeuroPace Responsive Neurostimulation (RNS) System is already approved in United States for the following indications:

Approved in United States as NeuroPace RNS System for:

• Epilepsy

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Andrew Krystal

Lead Sponsor

Trials

2

Recruited

10+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10314372/

The effect of responsive neurostimulation (RNS) on ... The goal of this study was to ascertain potential real-world effects of RNS on cognitive, psychiatric, and quality of life (QOL) outcomes in relation to seizure ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4233950/

Final results of the RNS System Pivotal trial - PMC Two-year seizure reduction in adults with medically intractable partial onset epilepsy treated with responsive neurostimulation: Final results of the RNS ...

3. neuropace.com neuropace.com/patients/neuropace-rns-system/

NeuroPace RNS System | Focal Epilepsy Treatment Device The estimated battery life of the RNS-320 Neurostimulator is nearly 11 years*. This means that on average you will likely be able to go over a decade after your ...

4. neuropace.com neuropace.com/providers/clinical-trials/

RNS System Clinical Trials The purpose of the RNS System Lennox-Gastaut Syndrome (LGS) study is to generate preliminary safety and effectiveness data for brain-responsive neurostimulation ...

5. neuropace.com neuropace.com/press-release/new-data-aes-2019-neuropace-rns-system/

New Data Presented at the American Epilepsy Society ... Real-world experience with the RNS System reveals best outcomes to date of any neuromodulation device for focal seizures.

6. neuropace.com neuropace.com/providers/rns-system-safety-data/

RNS System | Proven Safety Profile Responsive neurostimulation was well tolerated and safe over time. Conclusions from 9 years of data in the largest prospective neuromodulation study in the ...