Deep Brain Stimulation for Treatment-Resistant Depression

Overseen By Emma Meyer

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Helen Mayberg, MD

Must be taking: Antidepressants

Disqualifiers: Other Axis I, Suicidal ideation, others

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

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to help people with treatment-resistant depression using the Medtronic Summit RC+S DBS system, a deep brain stimulation device. The device sends electrical signals to a specific part of the brain to determine if it can alleviate depression symptoms. The study will also analyze brain signal patterns to better understand the treatment's mechanism. Participants should have a history of depression lasting over two years or more than three depressive episodes and live near New York City. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could lead to new insights and treatments for depression.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. However, since the trial involves treatment-resistant depression, it's possible that you may need to continue your current medications. Please consult with the study team for specific guidance.

What prior data suggests that this device is safe for treatment-resistant depression?

Research has shown that deep brain stimulation (DBS) using the Medtronic Summit RC+S has been explored for treating depression unresponsive to other treatments. In earlier studies, about 40-60% of patients experienced long-term relief from depression after receiving DBS, suggesting the treatment might work for some individuals.

The procedure involves placing tiny wires in the brain and a small device in the chest. Although this might sound complex, it has been used for conditions like Parkinson's disease, where it has significantly improved symptoms. This indicates that the treatment can be well-tolerated.

However, like any medical procedure, there are risks. Common side effects in similar treatments include headaches and temporary pain at the implantation site. Serious complications are less common but can include infection or issues with the device.

Overall, while researchers continue to study DBS, past research shows it can be safe for many people, with some experiencing significant benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Deep Brain Stimulation (DBS) using the Medtronic Summit RC+S system because it offers a novel approach for treatment-resistant depression, a condition where traditional treatments like antidepressants and psychotherapy often fall short. Unlike medications that target chemical imbalances in the brain, DBS delivers electrical impulses directly to specific areas of the brain to modulate its activity. This targeted approach has the potential to provide relief for patients who haven't responded to other therapies, offering hope for a quicker and more sustained improvement in mood and quality of life.

What evidence suggests that this device is effective for treatment-resistant depression?

Research has shown that deep brain stimulation (DBS) in the subcallosal cingulate (SCC) can significantly aid individuals with treatment-resistant depression (TRD). In studies where participants were aware of receiving DBS, about 40-60% experienced long-term relief from depression symptoms. This trial will employ the Medtronic Summit RC+S DBS system, which both stimulates the brain and records brain activity, enabling personalized treatment. These promising results position DBS as a hopeful option for those who haven't found relief with other treatments. ^{1 2 6 7 8}

Who Is on the Research Team?

Helen Mayberg, MD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

This trial is for adults aged 25-70 with severe, treatment-resistant Major Depressive Disorder (MDD), who have not responded to multiple treatments including medications and possibly ECT. They must be able to undergo an MRI, live near New York City, and have a caregiver to assist them. Pregnant individuals or those planning pregnancy, people with certain medical conditions or on anticoagulant therapy that can't be stopped are excluded.

Inclusion Criteria

Your overall level of functioning is assessed to be 50 or lower.

Ability to provide written informed consent

I have been diagnosed with Major Depressive Disorder without psychosis.

Exclusion Criteria

You have a heart device like a pacemaker or defibrillator that could be affected by the study treatment.

You have a medical condition that requires MRI scans or diathermy treatment.

I need anticoagulant therapy that can't be stopped for surgery.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Implantation and Initial Setup

Participants are implanted with the Summit RC+S system and initial device setup is conducted

1-2 weeks

1 visit (in-person)

Active Stimulation and Monitoring

Participants receive continuous active DBS stimulation and are monitored with weekly in-person assessments and twice-daily LFP data collection

1 year

Weekly visits (in-person)

Discontinuation Experiment

A brief discontinuation experiment is conducted after 6 months of stimulation to record LFP changes

1-2 weeks

Long-term Follow-up

Participants are monitored for long-term effects and device performance, expected to last up to 10 years

Up to 10 years

What Are the Treatments Tested in This Trial?

Interventions

• Medtronic Summit RC+S DBS system

Trial Overview The study tests the Medtronic Summit RC+S DBS system's ability to alleviate symptoms of severe depression by stimulating a brain region called the subcallosal cingulate. Participants will receive this experimental device implant and their brain activity will be monitored regularly over approximately ten years.

How Is the Trial Designed?

Group I: Deep Brain Stimulation (DBS) Experimental Treatment 1 Intervention

Open label active Deep Brain Stimulation (DBS)

Who Is Running the Clinical Trial?

Helen Mayberg, MD

Lead Sponsor

Trials

2

Recruited

20+

Emory University

Collaborator

Trials

1,735

Recruited

2,605,000+

Georgia Institute of Technology

Collaborator

Trials

53

Recruited

5,600+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Published Research Related to This Trial

Deep Brain Stimulation (DBS) of the medial forebrain bundle (MFB) in Flinders Sensitive Line (FSL) rats, which model depressive-like behavior, improved cognitive performance, specifically in memory tasks, without affecting other behaviors like exploration or vocalization.

The study indicates that while MFB DBS did not change certain depressive behaviors, it selectively enhanced cognitive abilities, suggesting a potential mechanism of action that may involve dopamine pathways, warranting further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of bilateral, continuous, and chronic Deep Brain Stimulation of the medial forebrain bundle in a rodent model of depression. Thiele, S., Furlanetti, L., Pfeiffer, LM., et al.[2018]

In a long-term study of 8 patients with treatment-resistant depression (TRD) who underwent deep brain stimulation (DBS), there was a significant average improvement of 44.9% in depression scores over an average follow-up of 11 years, with 50% of patients showing at least a 50% improvement.

Despite the potential benefits, the study also highlighted risks, including two patients discontinuing treatment due to lack of efficacy and one patient committing suicide after stopping stimulation, emphasizing the need for careful patient selection and monitoring in future DBS trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep Brain Stimulation of the Ventral Capsule/Ventral Striatum for Treatment-Resistant Depression: A Decade of Clinical Follow-Up. Hitti, FL., Cristancho, MA., Yang, AI., et al.[2021]

Deep brain stimulation (DBS) targeting the anterior nucleus of the thalamus (ANT) and hippocampus (HC) has been shown to significantly reduce seizure frequency in drug-resistant epilepsy, with about 50% of patients experiencing a 46%-90% reduction with ANT-DBS and a 48%-95% reduction with HC-DBS.

Approximately 75% of patients receiving stimulation from ANT, HC, or centromedian nucleus of the thalamus (CMT) report at least a 50% reduction in seizures, with factors like the absence of structural brain abnormalities and specific seizure types influencing the effectiveness of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for drug-resistant epilepsy. Li, MCH., Cook, MJ.[2018]

A review of 221 unique adverse events related to deep brain stimulation (DBS) devices for Parkinson's disease revealed that the most common complications were infections (16.2%) and lead migrations (8.6%).

Over 40% of the reported adverse events required patients to return to the operating room for device explantation or revision, highlighting the need for further research to improve the safety and reliability of DBS systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterizing Complications of Deep Brain Stimulation Devices for the Treatment of Parkinsonian Symptoms Without Tremor: A Federal MAUDE Database Analysis. Bennett, J., MacGuire, J., Novakovic, E., et al.[2023]

Medial forebrain bundle (MFB) deep brain stimulation (DBS) at specific parameters (100 μA, 90 μs, and high frequency) produced significant antidepressant-like effects in rats, as evidenced by improved performance in the forced swim test, a common measure of depression.

The stimulation increased activity in brain regions associated with reward, such as the nucleus accumbens and ventral tegmental area, but interestingly did not lead to increased dopamine or serotonin release in the nucleus accumbens, suggesting a unique mechanism of action for MFB DBS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antidepressant-like Effects of Medial Forebrain Bundle Deep Brain Stimulation in Rats are not Associated With Accumbens Dopamine Release. Bregman, T., Reznikov, R., Diwan, M., et al.[2019]

Deep brain stimulation (DBS) for Parkinson's disease is generally safe, with a low mortality rate of 0.2% and permanent morbidity at 0.6%, but complications such as intracerebral hemorrhage (ICH) and seizures can occur in a small percentage of cases.

The study found that the type of lead used in DBS can influence complications, with Medtronic's leads associated with higher rates of perielectrode brain edema compared to Boston Scientific's, highlighting the need for further research on hardware design to improve safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications of deep brain stimulation in Parkinson's disease: a single-center experience of 517 consecutive cases. Servello, D., Galbiati, TF., Iess, G., et al.[2023]

Deep Brain Stimulation (DBS) is a promising treatment option for patients with treatment-resistant depression, offering a minimally invasive way to regulate brain circuits associated with depression.

The article highlights the importance of understanding the complex mechanisms of depression to improve the effectiveness of DBS, while also addressing the challenges in its application and therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The Value of Deep Brain Stimulation in Difficult-To-Treat and Treatment-Refractory Depression]. Baumann-Vogel, H., Ineichen, C., Stieglitz, L., et al.[2023]

Deep brain stimulation (DBS) has shown a significant increase in response rates and reduction in depressive symptoms compared to sham treatment, based on a meta-analysis of 190 participants from nine studies.

Despite its promise for treatment-resistant depression, DBS is still considered experimental due to potential publication bias and the occurrence of serious adverse effects in some patients, indicating the need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review and meta-analysis of deep brain stimulation for depression. Kisely, S., Li, A., Warren, N., et al.[2019]

Deep brain stimulation (DBS) targeting the subcallosal cingulate cortex (SCC) shows promising efficacy for treatment-resistant depression (TRD), with response rates ranging from 23% to 92% and remission rates between 27% and 66.7% based on a review of 14 studies involving 230 patients.

The adverse effects associated with SCC DBS are generally transient and related to stimulation, indicating a favorable safety profile for this experimental treatment in TRD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcallosal Cingulate Cortex Deep Brain Stimulation for Treatment-Resistant Depression: A Systematic Review. Sobstyl, M., Kupryjaniuk, A., Prokopienko, M., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04106466

DBS for TRD With the Medtronic Summit RC+S This is believed to reset the brain network responsible for symptoms and results in a significant antidepressant response. A series of open-label studies have ...

2. centerwatch.com centerwatch.com/clinical-trials/listings/NCT04106466/dbs-for-trd-with-the-medtronic-summit-rcs

DBS for TRD With the Medtronic Summit RC+S A series of open-label studies have demonstrated sustained, long-term antidepressant effects in 40-60% of patients who received this treatment.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8312257/

Analysis-rcs-data: Open-Source Toolbox for the Ingestion, ... The Summit RC+S system consists of two surface or depth leads that are implanted in the brain and a neurostimulator (INS) implanted in the chest. The system is ...

4. aging.networkofcare.org aging.networkofcare.org/sanmateo/CommunityResources/ClinicalTrials/Detail/NCT04106466?keyword=%22Depressive%20Disorder%2C%20Treatment-Resistant%22

DBS for TRD With the Medtronic Summit RC+S The goal of this study is to study LFPs before and during active DBS stimulation to identify changes that correlate with the antidepressant effects of SCC DBS.~ ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT01984710

Deep Brain Stimulation for Treatment Resistant Depression ... The goal of this study is to use the Activa Primary Cell + Sensing (PC+S) device to study Latent Field Potential (LFP) in the brains of people with Treatment ...

6. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/66/NCT04106466/ICF_000.pdf

TITLE OF RESEARCH STUDY: The purpose of this research study is to use an experimental device, the Summit RC+S (Medtronic,. Inc), to measure changes in the electrical patterns in your ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9514741/

Initial Clinical Outcome With Bilateral, Dual-Target Deep ... Combined DBS improved PD symptom control, allowing >80% levodopa medication reduction. There was a greater decrease in off-medication motor Unified PD Rating ...

8. frontiersin.org frontiersin.org/journals/human-neuroscience/articles/10.3389/fnhum.2021.644593/full

Proceedings of the Eighth Annual Deep Brain Stimulation ... Stimulation of the subgenual cingulate has been shown to produce clinical benefits in patients with treatment resistant depression (Mayberg et al., 2005).