Deep Brain Stimulation for Depression
(PReSiDio Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: University of California, San Francisco
Must not be taking: Narcotics, Anticoagulants
Disqualifiers: Psychotic disorder, Substance abuse, Seizures, others
No Placebo Group
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?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.
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 data supports the idea that Deep Brain Stimulation for Depression is an effective treatment?
The available research shows that the NeuroPace Responsive Neurostimulation (RNS) System is primarily used for treating epilepsy, not depression. The studies focus on its effectiveness in controlling seizures for patients with epilepsy who do not respond to medication. There is no data provided here that supports its effectiveness for treating depression.
12345What safety data is available for Deep Brain Stimulation using the NeuroPace RNS System?
The NeuroPace RNS System is primarily used for treating epilepsy, specifically for patients with drug-resistant partial seizures. Safety data includes potential risks such as implant site infection and bone flap osteomyelitis. The system has been approved by the U.S. FDA, indicating a level of safety validation. However, long-term risks are not fully understood, and the available studies focus on epilepsy rather than depression.
12356Is the NeuroPace Responsive Neurostimulation System a promising treatment for depression?
Yes, the NeuroPace Responsive Neurostimulation System is a promising treatment for depression. It uses deep brain stimulation, which has shown to improve symptoms in people with treatment-resistant depression. Studies have reported long-term benefits, including better mood, reduced anxiety, and improved quality of life for many patients.
7891011Eligibility Criteria
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
+8 more
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)
+21 more
Trial Timeline
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
Participant Groups
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.
3Treatment groups
Experimental Treatment
Active Control
Placebo Group
Group I: Arm 1: Intervention (stimulation ON)Experimental Treatment1 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 Control1 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 Group1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of California, San FranciscoSan Francisco, CA
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Who Is Running the Clinical Trial?
University of California, San FranciscoLead Sponsor
Andrew KrystalLead Sponsor
References
Operative Technique and Lessons Learned From Surgical Implantation of the NeuroPace Responsive Neurostimulation® System in 57 Consecutive Patients. [2021]The Responsive Neurostimulation (RNS)® System (NeuroPace, Inc) is an implantable device designed to improve seizure control in patients with medically refractory focal epilepsy. Because it is relatively new, surgical pearls and operative techniques optimized from experience beyond a small case series have yet to be described.
Implantation of Responsive Neurostimulation for Epilepsy Using Intraoperative Computed Tomography: Technical Nuances and Accuracy Assessment. [2017]Implantation of responsive neurostimulation (RNS) system has been previously discussed in the literature but there is a paucity of data on target accuracy and the use of intraoperative imaging. We describe our experience with 8 patients using intraoperative computed tomography (iCT) during implantation of the NeuroPace RNS system.
The RNS System: brain-responsive neurostimulation for the treatment of epilepsy. [2021]Introduction: Epilepsy affects more than 1% of the US population, and over 30% of adults with epilepsy do not respond to antiseizure medications without life-impacting medication-related side effects. Resection of the seizure focus is not an option for many patients because it would cause unacceptable neurological or cognitive harm. For these patients, neuromodulation has emerged as a nondestructive, effective, and safe alternative. The NeuroPace® RNS® System, the only brain-responsive neurostimulation device, records neural activity from leads placed at one or two seizure foci. When the neurostimulator detects epileptiform activity, as defined for each patient by his or her physician, brief pulses of electrical stimulation are delivered to normalize the activity.Areas covered: This review describes the RNS System, the results of multi-year clinical trials, and the research discoveries enabled by the chronic ambulatory brain data collected by the RNS System.Expert commentary: Brain-responsive neurostimulation could potentially be used to treat any episodic neurological disorder that's accompanied by a neurophysiological biomarker of severity. Combining advanced machine learning approaches with the chronic ambulatory brain data collected by the RNS System could eventually enable automatic fine-tuning of detection and stimulation for each patient, creating a general-purpose neurotechnological platform for precision medicine.
Early detection rate changes from a brain-responsive neurostimulation system predict efficacy of newly added antiseizure drugs. [2021]Brain-responsive neurostimulation (RNS System, NeuroPace) is used to treat medically refractory focal epilepsy and also provides long-term ambulatory neurophysiologic data. We sought to determine whether these data could predict the clinical response to antiseizure drugs (ASDs).
A Novel Robotic-Assisted Technique to Implant the Responsive Neurostimulation System. [2021]The responsive neurostimulation system (RNS) (NeuroPace Inc, Mountain View, California) was approved as an adjunctive therapy for medically refractory focal epilepsy. RNS detects epileptiform patterns and delivers electrical stimulation to abort seizures.
Implant Site Infection and Bone Flap Osteomyelitis Associated with the NeuroPace Responsive Neurostimulation System. [2019]The NeuroPace RNS System is a method recently approved by the U.S. Food and Drug Administration for closed-loop direct brain stimulation in selected patients with drug-resistant partial seizures. The long-term risks of implant site infection and accompanying bone flap osteomyelitis associated with responsive neurostimulation (RNS) devices have not been fully appreciated.
Closed-loop neuromodulation in an individual with treatment-resistant depression. [2021]Deep brain stimulation is a promising treatment for neuropsychiatric conditions such as major depression. It could be optimized by identifying neural biomarkers that trigger therapy selectively when symptom severity is elevated. We developed an approach that first used multi-day intracranial electrophysiology and focal electrical stimulation to identify a personalized symptom-specific biomarker and a treatment location where stimulation improved symptoms. We then implanted a chronic deep brain sensing and stimulation device and implemented a biomarker-driven closed-loop therapy in an individual with depression. Closed-loop therapy resulted in a rapid and sustained improvement in depression. Future work is required to determine if the results and approach of this n-of-1 study generalize to a broader population.
Deep brain stimulation for major depression. [2013]A third of patients suffering from major depression cannot be helped by conventional treatment methods. These patients face reduced quality of life, high risk of suicide, and little hope of recovery. Deep brain stimulation (DBS) is under scientific evaluation as a new treatment option for these treatment-resistant patients. First clinical studies with small samples have been stimulated at the subgenual cingulate gyrus (Cg25/24), the anterior limb of the capsula interna (ALIC), and the nucleus accumbens (NAcc). Long-term antidepressant effects, augmentation of social functioning, and normalization of brain metabolism have been shown in about 50% of patients. Cognitive safety regarding attention, learning, and memory has been reported. Adverse events were wound infection, suicide, and hypomania, amongst others. Larger studies are under way to confirm these preliminary encouraging results. New hypothesis-guided targets (e.g., medial forebrain bundle, habenula) are about to be assessed in clinical trials. The application of DBS for other psychiatric diseases (e.g., bipolar disorder, alcohol dependency, opioid addiction, schizophrenia) is debated and single case studies are under way. Standards are needed for study registration, target selection, patient inclusion and monitoring, and publication of results to guarantee safety for the patients and scientific exchange.
Subcallosal Cingulate Cortex Deep Brain Stimulation for Treatment-Resistant Depression: A Systematic Review. [2022]Deep brain stimulation (DBS) is considered a relatively new and still experimental therapeutic modality for treatment-resistant depression (TRD). There is clinical evidence to suggest that stimulation of the subcallosal cingulate cortex (SCC) involved in the pathogenesis of TRD may exert an antidepressant effect.
Long-term effects of nucleus accumbens deep brain stimulation in treatment-resistant depression: evidence for sustained efficacy. [2021]Deep brain stimulation (DBS) to the nucleus accumbens (NAcc-DBS) was associated with antidepressant, anxiolytic, and procognitive effects in a small sample of patients suffering from treatment-resistant depression (TRD), followed over 1 year. Results of long-term follow-up of up to 4 years of NAcc-DBS are described in a group of 11 patients. Clinical effects, quality of life (QoL), cognition, and safety are reported. Eleven patients were stimulated with DBS bilateral to the NAcc. Main outcome measures were clinical effect (Hamilton Depression Rating Scale, Montgomery-Asperg Rating Scale of Depression, and Hamilton Anxiety Scale) QoL (SF-36), cognition and safety at baseline, 12 months (n=11), 24 months (n=10), and last follow-up (maximum 4 years, n=5). Analyses were performed in an intent-to-treat method with last observation carried forward, thus 11 patients contributed to each point in time. In all, 5 of 11 patients (45%) were classified as responders after 12 months and remained sustained responders without worsening of symptoms until last follow-up after 4 years. Both ratings of depression and anxiety were significantly reduced in the sample as a whole from first month of NAcc-DBS on. All patients improved in QoL measures. One non-responder committed suicide. No severe adverse events related to parameter change were reported. First-time, preliminary long-term data on NAcc-DBS have demonstrated a stable antidepressant and anxiolytic effect and an amelioration of QoL in this small sample of patients suffering from TRD. None of the responders of first year relapsed during the observational period (up to 4 years).
[Deep brain stimulation--the newest physical method of treatment of depression]. [2018]The deep brain stimulation DBS is the newest physical method of the treatment of depressive disorders. When applying of this technique in neurological illnesses (e.g., Parkinson's disease), mood changes were observed. In 2005, Helen Mayberg et al. used DBS in the therapy of the depression for the first time. Stimulating electrodes were placed in Brodmann areas 25. In the period of some past years, only about 30-40 patients with refractory depression have undergone DBS treatment. Numerous problems connected with applying DBS in patients with psychiatric disorders are described in the paper.