Deep Brain Stimulation for Treatment-Resistant Depression

Overseen By Jaimie Gowatsky, MA

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Helen Mayberg, MD

Must be taking: Antidepressants, Augmentation agents

Disqualifiers: Other Axis I, Neurological disorders, 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

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach called deep brain stimulation (DBS) to help individuals with treatment-resistant depression (TRD). The treatment involves placing a device in the brain to send electrical signals, potentially improving depression symptoms. Researchers use the Medtronic Percept PC DBS system to study brain signals and understand their relation to the treatment's effects. The trial seeks participants diagnosed with major depressive disorder (MDD) who have tried at least four different treatments without success. Participants must reside in the New York metropolitan area during the study's initial months.

As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could lead to new treatment options for depression.

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

The trial protocol does not specify whether you need to stop taking your current medications. However, it does require that you have not responded to at least four adequate antidepressant treatments, which suggests that you may continue some medications. It's best to discuss your specific situation with the study team.

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

Research has shown that deep brain stimulation (DBS) using the Medtronic Percept PC system holds promise for individuals with depression unresponsive to other treatments. The FDA has already approved this system for other uses, indicating its general safety. In studies where patients received DBS for depression, many tolerated it well over time. Most studies report lasting antidepressant effects in 40-60% of patients without serious side effects.

The Percept PC device is designed for safety and ease of use. It allows doctors to monitor brain activity and adjust treatment as needed, reducing potential risks. Although surgeries like DBS carry some risks, research indicates that serious complications are rare. Participants in previous studies have mostly reported only mild issues, if any. This evidence suggests that DBS with the Percept PC is generally well-tolerated by patients. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about deep brain stimulation (DBS) for treatment-resistant depression because it offers a new way to tackle this stubborn condition. Most current treatments, like antidepressants and therapy, work by altering brain chemistry or behavior, but DBS takes a different approach by directly stimulating specific brain areas with electrical impulses. This method has the potential to precisely target brain circuits involved in depression, possibly providing relief for individuals who haven’t responded to other treatments. The use of the Medtronic Percept PC DBS system is particularly promising because it can continuously monitor brain activity and adjust stimulation accordingly, potentially leading to more personalized and effective treatment.

What evidence suggests that the Medtronic Percept PC DBS system is effective for treatment-resistant depression?

Research has shown that deep brain stimulation (DBS) in the subcallosal cingulate (SCC) can significantly benefit individuals with treatment-resistant depression (TRD). Studies have found that 40-60% of patients receiving this treatment experience lasting relief from depression. This trial will use the Medtronic Percept PC DBS system, which involves placing small wires in the brain and using electrical signals to "reset" the brain's network, easing depression symptoms. The Medtronic Percept PC device also records brain signals, aiding in treatment adjustments for better results. Overall, evidence supports DBS as a promising option for those who haven't found relief from other depression treatments. ^{1 3 5 6 7}

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 living in the New York area with Major Depressive Disorder (MDD) that hasn't improved after trying at least four different treatments. They should be experiencing a severe depressive episode lasting two years or have had more than three episodes. Participants must be able to follow study procedures and give written consent.

Inclusion Criteria

Ability to provide written informed consent

Minimum score at study entry of 20 on the 17-item Hamilton Depression Rating Scale

A maximum Global Assessment of Functioning of 50 or less

Exclusion Criteria

Currently implanted with a cardiac pacemaker/defibrillator or other implanted electrical device which may interfere with DBS stimulator or the function of which may be impacted by its implantation

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

Other primary Axis I conditions

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Implantation and Initial Assessment

Participants are implanted with the Percept PC system and initial assessments are conducted

4 weeks

Weekly in-person visits

Active Stimulation and Monitoring

Participants receive active DBS stimulation and are monitored with weekly assessments and LFP data collection

1 year

Weekly in-person visits, daily LFP data collection

Discontinuation Experiment

Stimulation is briefly turned off after 6 months to record LFP changes

1-2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 years

What Are the Treatments Tested in This Trial?

Interventions

• Medtronic Percept PC DBS system

Trial Overview The trial tests Deep Brain Stimulation (DBS) using the Medtronic Percept PC system on patients with treatment-resistant depression. It involves placing electrodes in the brain and stimulating it to potentially alleviate symptoms. The study also aims to identify biomarkers related to DBS effectiveness.

How Is the Trial Designed?

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

Open label active Deep Brain Stimulation (DBS)

Medtronic Percept PC DBS system is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Percept PC neurostimulator for:

• Parkinson’s disease
• essential tremor
• primary dystonia
• epilepsy

Approved in United States as Percept PC neurostimulator for:

• Parkinson’s disease
• essential tremor
• primary dystonia
• epilepsy

Approved in Japan as Percept PC neurostimulator for:

• Parkinson’s disease
• essential tremor
• primary dystonia
• epilepsy

Who Is Running the Clinical Trial?

Helen Mayberg, MD

Lead Sponsor

Trials

2

Recruited

20+

Published Research Related to This Trial

Deep brain stimulation (DBS) shows promise as a treatment for patients with major depression who do not respond to conventional therapies, with about 50% of patients experiencing long-term antidepressant effects and improved social functioning.

While cognitive safety regarding attention, learning, and memory has been reported, there are potential adverse events such as wound infection and suicide, highlighting the need for larger studies to confirm safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for major depression. Schlaepfer, TE., Bewernick, BH.[2013]

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]

In a study of 27 Parkinson's disease patients with deep brain stimulation, the use of a patient controller (PC) was found to enhance the ability to optimize stimulation amplitudes and improve patients' perception of safety, despite not being essential for safety.

While no accidental switch-offs of the device due to environmental factors were reported, some patients did accidentally turn off their implantable pulse generator (IPG) using the PC, highlighting the need for careful use of the device.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is a patient controller for Parkinson's disease patients with subthalamic nucleus deep brain stimulation reasonable? Allert, N., Mehnert, C., Lehrke, R., et al.[2015]

The Percept™ PC platform by Medtronic represents a significant advancement in deep brain stimulation (DBS) technology, featuring brain sensing capabilities that allow for real-time monitoring and optimization of therapeutic stimulation.

This device not only enhances patient experience with improved battery life and MRI compatibility but also aims to refine treatment by correlating symptoms with neurophysiological data, although further research is needed to fully establish its clinical benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Device profile of the percept PC deep brain stimulation system for the treatment of Parkinson's disease and related disorders. Jimenez-Shahed, J.[2021]

In a study of 8 patients with treatment-resistant depression, deep brain stimulation (DBS) showed promising short-term results, with 87.5% of patients responding and 50% achieving remission within the first week after surgery.

At the one-year mark, 62.5% of patients still showed a response to treatment, and 50% were in remission, indicating that DBS can be a viable long-term therapeutic option for patients who do not respond to traditional treatments, with minimal side effects reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation of the subcallosal cingulate gyrus: further evidence in treatment-resistant major depression. Puigdemont, D., Pérez-Egea, R., Portella, MJ., et al.[2021]

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]

The Medtronic 'Percept' device, the first FDA-approved deep brain stimulation system with sensing capabilities, was tested on 7 subjects to identify and mitigate artifacts in local field potential signals that could affect its performance.

Using automated template subtraction techniques, researchers successfully removed various artifacts, such as ECG signals and nonphysiologic noise, which could otherwise distort the neural signals and impact the effectiveness of adaptive deep brain stimulation algorithms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Artifact Characterization and a Multipurpose Template-Based Offline Removal Solution for a Sensing-Enabled Deep Brain Stimulation Device. Hammer, LH., Kochanski, RB., Starr, PA., et al.[2023]

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]

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]

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) 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/NCT05773755

NCT05773755 | DBS for TRD with the Medtronic Percept PC A series of open-label studies have demonstrated sustained, long-term antidepressant effects in 40-60% of patients who received this treatment. A challenge to ...

2. pacificneuroscienceinstitute.org pacificneuroscienceinstitute.org/movement-disorders/wp-content/uploads/sites/7/2020/12/US-Percept-Media-Kit-US-FY21-FINAL.pdf

MEDTRONIC PERCEPT™ PC NEUROSTIMULATOR ... • Long-term safety and effectiveness for DBS Therapy for Epilepsy was established through 2–7 years.4-7. • At 7-years, patients experienced a median 75 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11524207/

Current and future applications of local field potential-guided ... Deep brain stimulation (DBS) has been established as an effective neuromodulatory treatment for Parkinson's disease (PD) with motor complications or ...

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

P960009/S478 Summary of Safety and Effectiveness (SSED) The study was a prospective, multicenter, single-arm, aDBS treatment mode blind, randomized crossover trial in subjects with Parkinson's Disease and DBS leads.

5. medtronic.com medtronic.com/content/dam/medtronic-wide/public/united-states/products/neurological/deep-brain-stimulation/brainsense-compendium-white-paper.pdf

BrainSense™ Technology Scientific Compendium The Percept™ PC and Percept™ RC neurostimulators with BrainSense™ technology capture brain signals (LFPs) using an implanted deep brain stimulation (DBS) lead(s) ...

6. medtronic.com medtronic.com/en-us/healthcare-professionals/products/neurological/deep-brain-stimulation/electrical-stimulation-systems/percept-pc-neurostimulator.html

Percept™ PC Neurostimulator The Percept™ PC is a recharge free neurostimulator with sensing, directionality, and advanced programming capabilities for deep brain stimulation (DBS).

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02046330

Deep Brain Stimulation (DBS) Therapy for Treatment ... We propose a clinical study of medial forebrain bundle DBS as a treatment in 20 patients with treatment refractory depression (TRD). Data from the ...