DBS for Depression

Overseen By Samantha Gonzalez

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Northwell Health

Must not be taking: Anticoagulants

Disqualifiers: Psychosis, Substance abuse, Pregnancy, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 12 months

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether deep brain stimulation (DBS), a procedure involving the implantation of a device to send electrical signals to specific brain areas, can aid individuals with severe depression unresponsive to other treatments. The goal is to determine if DBS can reduce depression symptoms and enhance overall well-being. Participants will have the device activated and deactivated at various times to assess its effectiveness. The trial seeks individuals who have experienced major depression for over five years, have tried multiple treatments without success, and face significant daily life challenges due to their condition. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this innovative approach.

Will I have to stop taking my current medications?

The trial requires participants to be on a stable psychiatric medication regimen for at least 6 weeks before joining and to continue this regimen for the first 6 months. Changes to medications can be made during the study based on the clinical judgment of the study psychiatrist.

What prior data suggests that this deep brain stimulation device is safe for treating depression?

Research shows that deep brain stimulation (DBS) has been safely used in conditions like epilepsy. The Medtronic SenSight Directional DBS lead, the device used in this study, has been part of these treatments. People with epilepsy who used similar DBS systems experienced fewer seizures and tolerated the device well.

However, like any medical device, some risks exist. Serious side effects can include tissue damage from the device heating up, potentially causing severe injury. These events, though, are rare. Since this trial is in its early stages, its main goal is to ensure the treatment's safety for people with depression that hasn't responded to other treatments.

Overall, existing research suggests DBS can be a safe option, but this trial will help confirm that for this specific use. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

The Medtronic SenSight Directional DBS lead is unique because it offers a precise and adjustable method for treating depression. Unlike traditional antidepressants, which work by altering brain chemistry, this device provides direct electrical stimulation to specific brain regions involved in mood regulation. Researchers are excited about this treatment because it allows for customization of the stimulation parameters, potentially leading to more effective and personalized outcomes for patients who haven't responded to conventional therapies. Additionally, this method can deliver rapid improvements in depressive symptoms, offering hope for quicker relief compared to the weeks or months often required with standard medications.

What evidence suggests that this device is effective for depression?

Research has shown that deep brain stimulation (DBS) can improve symptoms in people with treatment-resistant depression. This trial will explore different parameter settings of directional DBS, which sends focused electrical signals to specific brain areas, to enhance its positive effects. Participants will be randomized into two groups to analyze these settings. Early results suggest that active DBS may reduce depression symptoms more effectively than inactive DBS. This indicates that DBS could potentially improve overall well-being and daily functioning in people with this type of depression. ^{1 2 6 7 8}

Who Is on the Research Team?

Albert J Fenoy, MD

Principal Investigator

Northwell Health

Are You a Good Fit for This Trial?

This trial is for adults aged 22-70 with severe, treatment-resistant depression. They must have tried multiple medications, psychotherapy, and possibly ECT without success. Participants need to be stable on their current meds and willing to be monitored over 5 years. Exclusions include those with psychosis history, unstable living situations, certain medical conditions or contraindications for surgery.

Inclusion Criteria

Your ability to function in daily life is very low, based on a special score called the Global Assessment of Function (GAF) score.

Patients with a history or diagnosis of generalized anxiety disorder (GAD) at the time of enrollment so long as Major Depressive Disorder (MDD) is the primary psychiatric diagnosis in the medical opinion of an investigator

At enrollment, provides the following information from at least two (2) verifiable contacts who reside within a 10-mile radius of the patient: name, relationship to patient, address (email mail); and telephone (mobile, home, work as applicable)

Exclusion Criteria

Within the past six months, you have been diagnosed with a substance abuse problem according to the guidelines used by doctors.

You have a condition that requires regular MRI scans.

I am currently taking medication to prevent blood clots.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Device Implantation

Participants are implanted with a deep brain stimulation device

1 week

1 visit (in-person)

Treatment

Participants undergo treatment with the DBS device, which is ON for 8.5 months and OFF for 3.5 months during the first year

12 months

Regular monitoring visits

Discontinuation Phase

Participants are randomized into two groups for crossover treatment analysis of different parameter settings

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 years

What Are the Treatments Tested in This Trial?

Interventions

• Medtronic SenSight Directional DBS lead

Trial Overview Researchers are testing a Medtronic SenSight Directional DBS lead device implanted in participants to treat resistant depression. Over five years, the device's effectiveness will be assessed by turning it off at random times without participants' knowledge and comparing their questionnaire scores during these periods.

How Is the Trial Designed?

Group I: Discontinuation Phase Group 2 Experimental Treatment 1 Intervention

Patients will be randomized into two groups for crossover treatment analysis of different parameter settings for six weeks.

Group II: Discontinuation Phase Group 1 Experimental Treatment 1 Intervention

Patients will be randomized into two groups for crossover treatment analysis of different parameter settings for six weeks.

Medtronic SenSight Directional DBS lead is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Deep Brain Stimulation for:

• Parkinson’s disease
• Epilepsy
• Essential tremor
• Dystonia
• Obsessive-compulsive disorder

Approved in United States as Deep Brain Stimulation for:

• Parkinson’s disease
• Epilepsy
• Essential tremor
• Dystonia
• Obsessive-compulsive disorder

Approved in Canada as Deep Brain Stimulation for:

• Parkinson’s disease
• Epilepsy
• Essential tremor
• Dystonia
• Obsessive-compulsive disorder

Who Is Running the Clinical Trial?

Northwell Health

Lead Sponsor

Trials

481

Recruited

470,000+

Medtronic

Industry Sponsor

Trials

627

Recruited

767,000+

Geoff Martha

Medtronic

Chief Executive Officer since 2020

Finance degree from Penn State University

Dr. Richard Kuntz

Medtronic

Chief Medical Officer since 2023

MD, MSc

Published Research Related to This Trial

Directional deep brain stimulation (DBS) leads show significantly higher impedance compared to conventional ring leads, which may impact their effectiveness and patient management.

In a study of 11 Parkinson's patients, impedance levels varied over time, with stimulated contacts consistently showing lower impedance than non-stimulated ones, indicating that monitoring impedance is crucial for optimizing DBS therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain impedance variation of directional leads implanted in subthalamic nuclei of Parkinsonian patients. Eleopra, R., Rinaldo, S., Devigili, G., et al.[2020]

Directional deep brain stimulation (DBS) using novel leads allows for more precise targeting of electrical stimulation, which can reduce unintended side effects and improve treatment outcomes for drug-resistant involuntary movements.

The complexity of programming these directional leads necessitates new strategies, including image-guided programming and potential future use of local field potentials for optimal stimulation, enhancing the effectiveness of DBS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgical Strategy for Directional Deep Brain Stimulation. Masuda, H., Shirozu, H., Ito, Y., et al.[2022]

In a study involving 14 patients with Parkinson's disease, the combination of intraoperative local field potentials (LFPs) beta power and neuroimaging reconstructions effectively predicted the most clinically effective stimulation contacts for deep brain stimulation (DBS), achieving a sensitivity of 87%.

Using LFPs beta power alone showed a sensitivity of 67% and a negative predictive value of 84%, indicating that this method can help identify effective contacts, potentially streamlining the DBS programming process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative Local Field Potential Beta Power and Three-Dimensional Neuroimaging Mapping Predict Long-Term Clinical Response to Deep Brain Stimulation in Parkinson Disease: A Retrospective Study. di Biase, L., Piano, C., Bove, F., et al.[2023]

In a study of 18 patients with directional deep brain stimulation (DBS) electrodes, the orientation of the leads remained stable over time, with an average change of only -1.1 ± 3.9° from the initial measurement.

This stability suggests that once implanted, the directional leads do not significantly drift in orientation, which is important for optimizing stimulation settings and ensuring consistent therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temporal Stability of Lead Orientation in Directional Deep Brain Stimulation. Dembek, TA., Asendorf, AL., Wirths, J., et al.[2021]

In a study of 100 patients with 198 directional deep brain stimulation (DBS) leads, significant deviations from the intended implantation direction were common, with 42% of leads deviating more than 30° and about 11% deviating more than 60°.

These deviations were not influenced by the neuroanatomical target or the stereotactic frame used, but were affected by the specific microdrive, highlighting the importance of postoperative lead orientation assessment for effective directional DBS therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Directional DBS leads show large deviations from their intended implantation orientation. Dembek, TA., Hoevels, M., Hellerbach, A., et al.[2020]

In a study of 52 Parkinson's disease patients using directional deep brain stimulation (DBS), 35% of the tested contacts showed a larger therapeutic window with directional stimulation compared to traditional ring-mode, indicating potential benefits of this approach.

The study developed a prediction model that can identify which contacts may benefit from directional stimulation with a sensitivity of 79%, helping to streamline the programming process and reduce the time needed for effective DBS adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep Brain Stimulation: When to Test Directional? Debove, I., Petermann, K., Nowacki, A., et al.[2023]

Directional deep brain stimulation (dDBS) was effectively implemented in 42 patients with movement disorders, showing a significant average reduction of 35.4% in levodopa-equivalent daily dose for Parkinson's disease patients six months post-implantation.

Despite the benefits of dDBS, accurate surgical placement is crucial, as 10 leads in 6 patients required revision due to electrode malposition, highlighting the importance of precision in achieving optimal clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Institutional Experience of Directional Deep Brain Stimulation and a Review of the Literature. Mishra, A., Unadkat, P., McBriar, JD., et al.[2023]

In a study of 107 patients undergoing Implantable Pulse Generator (IPG) replacement for Deep Brain Stimulation (DBS), a careful surgical technique was employed that successfully avoided errors in lead connection and laterality changes, which are common issues during such procedures.

The mean surgery duration was only 25 minutes, and all patients experienced stable symptoms post-replacement, indicating that with proper management, IPG replacement can be performed safely and effectively without extended hospitalization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How to avoid trivial mistakes during IPG replacement in patients treated with DBS for movement disorders: technical note from 13-years experience. Latini, F., Sensi, M., Preda, F., et al.[2015]

In a study involving six parkinsonian patients, directional leads for deep brain stimulation (DBS) showed a low incidence of adverse effects, particularly when stimulating in the posteromedial direction of the subthalamic nucleus (STN).

DBS significantly improved motor function and reduced dyskinesia, as evidenced by a decrease in Unified Parkinson's Disease Rating Scale (UPDRS) scores from 30.2 to 7.2 for motor symptoms and from 3.3 to 0.5 for dyskinesia after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot Study for Considering Subthalamic Nucleus Anatomy during Stimulation Using Directional Leads. Asahi, T., Ikeda, K., Yamamoto, J., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06096207

Study Details | NCT06096207 | DBS for Depression The goal of this clinical trial is to demonstrate the feasibility and safety of deep brain stimulation in treatment resistant depression.

2. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06096207/dbs-for-depression

DBS for Depression | Clinical Research Trial Listing The goal of this clinical trial is to demonstrate the feasibility and safety of deep brain stimulation in treatment resistant depression.

3. withpower.com withpower.com/trial/phase-1-depression-9-2023-bdaa9

DBS for Depression · Recruiting Participants for Phase ... Directional deep brain stimulation (DBS) has been shown to improve clinical benefits by better directing electrical currents, which can enhance the therapeutic ...

4. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/pdf/P960009S478B.pdf

P960009/S478 Summary of Safety and Effectiveness (SSED) Medtronic DBS therapy uses an implantable multi-programmable neurostimulation system to deliver electrical stimulation to selected areas of the brain. The major.

5. 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 ( ...

6. europe.medtronic.com europe.medtronic.com/xd-en/healthcare-professionals/therapies-procedures/neurological/deep-brain-stimulation/indications-safety-warnings.html

Deep Brain Stimulation - Indications, Safety, and Warnings The Medtronic DBS System for Epilepsy has demonstrated safety and effectiveness for patients who average six or more seizures per month over the three most ...

7. medtronic.com medtronic.com/en-us/healthcare-professionals/products/neurological/deep-brain-stimulation/dbs-therapy-leads/sensight-directional-lead.html

SenSight™ Directional Lead The SenSight™ directional DBS lead system combines the benefits of directionality with the power of sensing.

8. sciencedirect.com sciencedirect.com/science/article/pii/S2214751925000477

Innovative developments in deep brain stimulation devices The “SenSight™ directional lead (Medtronic) is a quadripolar lead with two external rings contact and two intermediate contacts, each of them consisting of ...