Deep Brain Stimulation for Depression

Recruiting at 1 trial location

Overseen By Sameer Sheth, PhD, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Baylor College of Medicine

Must be taking: Antidepressants

Must not be taking: Anticoagulants

Disqualifiers: Psychotic disorder, Bipolar, Substance use, 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: Unknown

Duration: 54 to 60 months

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach for individuals with treatment-resistant depression (TRD) using directional deep brain stimulation (DBS). Researchers aim to determine if this method can precisely target and influence brain networks related to depression, potentially improving symptoms. The trial will also evaluate the safety and effectiveness of this personalized DBS treatment. Individuals who have experienced major depression for over two years, have not found relief from at least four different treatments, and have tried electroconvulsive therapy (ECT) without lasting success may be suitable candidates for this study. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research in depression treatment.

Will I have to stop taking my current medications?

The trial requires that you have a stable antidepressant medication regimen for the month before surgery, so you may not need to stop your current medications if they are stable. However, if you are on chronic anticoagulant or anti-platelet agents, you may need to stop them for at least 2.5 weeks around the time of surgery.

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

Research has shown that deep brain stimulation (DBS) is generally safe and well-tolerated for people with depression that hasn't improved with other treatments. Studies have found that DBS can help those who haven't found relief with other methods. Although some side effects, such as speech problems or muscle contractions, can occur, they are uncommon. Overall, evidence suggests that DBS is a promising and safe experimental treatment for people with this type of depression. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for depression, such as antidepressant medications and psychotherapy, Directional Deep Brain Stimulation (DBS) offers a unique approach by directly targeting specific brain regions. This method uses advanced technology to more precisely deliver electrical impulses to the brain, potentially improving effectiveness and minimizing side effects. Researchers are excited about Directional DBS because it allows for personalized treatment, adjusting the stimulation to the individual's needs, which could lead to better outcomes for patients who have not responded to traditional therapies.

What evidence suggests that this device is effective for depression?

Research has shown that deep brain stimulation (DBS) can effectively help people with treatment-resistant depression. In past studies, DBS helped about 60% of these patients feel better, with most noticing some improvement in their symptoms. While DBS can address various aspects of depression, improvements in sleep might take longer. This trial studies a type of DBS called directional DBS, which precisely targets specific brain areas, to potentially reduce depression symptoms more effectively. Overall, early findings suggest that DBS could be a promising option for those with severe depression. ^{2 3 6 7 8}

Who Is on the Research Team?

Sameer Sheth, PhD, MD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

This trial is for adults aged 22-70 with major depressive disorder (MDD) who haven't improved after trying at least four different depression treatments and ECT or psychotherapy. They must have a stable medication regimen, normal brain MRI, no bipolar or certain personality disorders, no recent substance abuse, and not be pregnant.

Inclusion Criteria

I have been diagnosed with major depression as my main health issue.

Modified mini-mental state examination (MMSE) score ≥ 24

Able and willing to give informed consent and attend regular clinic visits for at least 12 months following surgery

Exclusion Criteria

Alcohol or substance use disorder within 6 months, excluding nicotine

I have a health condition that makes surgery risky for me.

I cannot have surgery due to a medical condition like an infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Subacute Neurophysiological Monitoring

Subacute invasive neurophysiological monitoring to gain insight into the networks underlying depression symptomatology

4-8 weeks

Treatment

Chronic DBS using steered, individualized targeting to reduce depressive symptoms

54 to 60 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Directional Deep Brain Stimulation

Trial Overview The study tests a new type of Deep Brain Stimulation (DBS) that directs electrical currents to specific brain networks linked to depression. It aims to show this method can change behavior by targeting these networks and is safe for long-term use in reducing symptoms of severe depression.

How Is the Trial Designed?

Group I: Directional Deep Brain Stimulation Experimental Treatment 1 Intervention

Directional Deep Brain Stimulation is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Deep Brain Stimulation for:

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

Approved in European Union as Deep Brain Stimulation for:

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

Approved in Canada as Deep Brain Stimulation for:

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

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

University of Texas

Collaborator

Trials

193

Recruited

143,000+

Published Research Related to This Trial

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]

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 53 patients with advanced Parkinson's disease, directional deep brain stimulation (dDBS) led to a significant 44% improvement in motor symptoms (measured by UPDRS-III) and a 43% reduction in medication dosage over 6 months, with sustained benefits at 18 months.

dDBS not only improved motor symptoms but also alleviated non-motor symptoms, demonstrating its effectiveness and safety in real-life clinical settings, with minimal adverse effects reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-Life Experience on Directional Deep Brain Stimulation in Patients with Advanced Parkinson's Disease. Koivu, M., Scheperjans, F., Eerola-Rautio, J., et al.[2022]

In a study of 74 patients with Parkinson's disease and essential tremor, 39-68% of patients with Parkinson's and 50-72% with essential tremor utilized directional deep brain stimulation (d-DBS) over 36 months to improve symptom control and reduce side effects.

Directional stimulation was preferred initially in essential tremor patients due to simpler programming, but as experience grew, more Parkinson's patients also benefited from d-DBS, highlighting its potential for better therapeutic outcomes compared to traditional omnidirectional stimulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Clinical Experience with Directional Deep Brain Stimulation Programming: A Retrospective Review. Karl, JA., Joyce, J., Ouyang, B., et al.[2022]

In a study of 51 patients with Parkinson's disease, dystonia, and tremor, 54.9% were using advanced features of directional deep brain stimulation (DBS) after 15 months, indicating a significant uptake of these features among patients who were selected based on specific clinical characteristics.

Advanced DBS features were particularly beneficial for patients implanted in the Vim region, with 92% utilizing these features, compared to 44% in the STN and 40% in the GPi, suggesting that the choice of target may influence the need for advanced stimulation options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The actual use of directional steering and shorter pulse width in selected patients undergoing deep brain stimulation. Zitman, FMP., Janssen, A., van der Gaag, NA., et al.[2022]

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 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]

Citations

1. 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, ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1878747925001011

Deep brain stimulation improves symptoms across all ... Our findings demonstrate that DBS for TRD effectively treats depressive symptoms in all dimensions, although insomnia symptoms may improve at a slower rate.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9410362/

Real-Life Experience on Directional Deep Brain ... We reviewed the clinical data of 53 PD patients with dDBS to 18 months of follow-up. Directional stimulation was favored in 70.5% of dDBS leads, ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03437928

Study Details | NCT03437928 | DBS for Depression The goal of the study is to address the unmet need of TRD patients by identifying brain networks critical for treating depression and to use next generation ...

5. jnnp.bmj.com jnnp.bmj.com/content/early/2024/09/20/jnnp-2024-333947?utm_source=twitter&utm_medium=paid&utm_campaign=usage&utm_content=bau_article_ads&utm_id=BMJ024

Directional deep brain stimulation electrodes in Parkinson's ... This review revealed an improvement of 39% (95% CI 36.9% to 41.2%) (UPDRS III baseline to OFF medication/ON stimulation) for directional electrodes on a ring ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6397644/

Deep brain stimulation: current challenges and future directions Although early case series showed promising effects of DBS in patients with treatmentrefractory depression, the outcomes of large controlled clinical trials ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1094715921064230

Directional Deep Brain Stimulation for Parkinson's Disease Potential side effects of chronic STN stimulation can include speech impairment, reduced verbal fluency, involuntary eye movement, muscle contraction, postural ...

8. nature.com nature.com/articles/s41531-024-00812-0

Randomized crossover trial on motor and non ... This prospective randomized cross-over trial compared omnidirectional (OS) and directional (DS) subthalamic DBS in 19 patients.