DBS for Depression

Overseen By Jenna Schugart

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

Trial Summary

What is the purpose of this trial?

This trial aims to test if deep brain stimulation can help people with treatment-resistant depression. The device is implanted in the brain and sends electrical signals to control mood. Researchers will monitor patients over several years to see if it reduces depression symptoms. Deep brain stimulation (DBS) has a decades-long history in psychiatric neurosurgery and has shown promise for treatment-resistant depression.

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 data supports the effectiveness of this treatment for depression?

Directional deep brain stimulation (DBS) has been shown to improve clinical benefits by better directing electrical currents, which can enhance the therapeutic effect and reduce side effects. This has been observed in patients with movement disorders, suggesting potential benefits for other conditions like depression. ^{1 2 3 4 5}

Is Deep Brain Stimulation (DBS) safe for humans?

Research shows that while DBS can have side effects, using directional leads may help reduce these by allowing more precise control of the stimulation. However, adverse events can occur, especially during device replacements, so careful management is important. ^{1 2 5 6 7}

How is the Medtronic SenSight Directional DBS lead treatment different from other depression treatments?

The Medtronic SenSight Directional DBS lead is unique because it uses directional leads that allow for precise control of the stimulation field, which can reduce side effects and improve effectiveness compared to traditional DBS systems. This technology also requires less electrical power and can be adjusted more accurately to target specific brain areas, potentially offering better outcomes for patients with depression. ^{1 3 5 8 9}

Research Team

Albert J Fenoy, MD

Principal Investigator

Northwell Health

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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 (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 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 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]

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]

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]

References

1. Korea (South) pubmed.ncbi.nlm.nih.gov

Pilot Study for Considering Subthalamic Nucleus Anatomy during Stimulation Using Directional Leads. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Directional DBS leads show large deviations from their intended implantation orientation. [2020]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Brain impedance variation of directional leads implanted in subthalamic nuclei of Parkinsonian patients. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

An Institutional Experience of Directional Deep Brain Stimulation and a Review of the Literature. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Temporal Stability of Lead Orientation in Directional Deep Brain Stimulation. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Deep Brain Stimulation: When to Test Directional? [2023]

7. England 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. [2015]

8. Japan pubmed.ncbi.nlm.nih.gov

Surgical Strategy for Directional Deep Brain Stimulation. [2022]

9. United States 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. [2023]