Epidural Cortical Stimulation for Depression

(EpCS-D Trial)

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Medical University of South Carolina

Must not be taking: Theophylline, Stimulants, Bupropion, others

Disqualifiers: Cardiac problems, Stroke, Seizure, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: up to 1 year

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to help individuals with severe depression who haven't found relief with other treatments. It uses epidural cortical stimulation, which involves placing a small wire on the brain's surface to send electrical signals to the area involved in mood regulation. The trial seeks individuals who have experienced depression for at least two years and have not responded well to at least four different antidepressant treatments. Participants should not have a history of serious heart or lung issues, seizures, or certain other health conditions.

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

Will I have to stop taking my current medications?

The trial requires that you stay on your current antidepressant medication schedule for the first 19 weeks, as long as you have been stable on them for at least 4 weeks before starting the study. However, you cannot be on medications known to increase the risk of seizures, like theophylline, stimulant medications, bupropion, or high doses of thyroid supplements.

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

Research has shown that epidural cortical stimulation (EpCS), like the Synergy device used in this trial, has been studied for its safety in treating depression. Previous studies found that EpCS is generally well-tolerated, with patients not reporting any serious side effects affecting cognitive processing. However, some studies did not report all safety details, which should be considered.

In a five-year follow-up study, patients who received this treatment for depression did not experience any major safety issues over the long term, suggesting the procedure could be safe for many people. Notably, EpCS has also been used in other medical treatments, such as for severe pain, which contributes to understanding its safety.

Overall, EpCS appears to be a safe option, but discussing any concerns with a healthcare provider before deciding to join a trial is always best. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for depression, such as antidepressants or psychotherapy, Synergy employs epidural cortical stimulation, a cutting-edge technique that targets the brain's medial prefrontal cortex directly. This method is particularly promising for those with treatment-resistant depression, as it offers a new way to potentially improve mood by modulating brain activity in a specific area associated with emotional regulation. Researchers are excited about this approach because it represents a novel mechanism of action and could provide a new option for patients who haven't responded to existing therapies.

What evidence suggests that this technique is effective for depression?

Research has shown that epidural cortical stimulation (ECS), which participants in this trial will receive, could help people with depression that hasn't improved with other treatments. In one study, patients experienced a 54.9% reduction in depression symptoms after 7 months. Another review found that 40-60% of patients responded well to this treatment. The procedure involves placing a small wire on the brain's surface to help control mood by targeting a part of the brain important for mood regulation. While more research is needed, these early results suggest ECS could be a promising option for those who haven't found relief with other treatments. ^{1 3 6 7 8}

Who Is on the Research Team?

Edward B Short, MD, MSCR

Principal Investigator

Medical University of South Carolina

Are You a Good Fit for This Trial?

This trial is for adults aged 21-80 with severe depression lasting two years or more, or those who have had multiple episodes. They must have tried and not responded to at least four different antidepressant treatments and can't be on certain medications that increase seizure risk. Participants should be stable on their current meds, able to undergo functional imaging scans, and have previously had a successful course of ECT.

Inclusion Criteria

I can stick to my current medication schedule for the first 19 weeks of the study.

I haven't improved after 4 or more depression treatments.

Subject must provide written informed consent

Exclusion Criteria

The EpCS would (in the investigator's judgment) pose an unacceptable surgical or medical risk for the patient (including, but not limited to: history of serious cardiac or pulmonary problems, stroke, significant brain malformation, progressive neurological disease, central nervous system disease or injury, history of seizure, previous neurosurgical procedure with suspected brain tissue scarring that would increase the risks for seizure or cervical fracture)

Subject currently has another investigational device or cardiac pacemaker, implantable defibrillator, or other implantable stimulator

Subject is judged by the investigator to be acutely suicidal (e.g. within the 30 days prior to the EpCS implant, the subject has made a suicide attempt or gesture or has made specific plans or preparation to commit suicide)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Placebo Lead-in

Participants undergo a 1-month placebo lead-in period before receiving the actual treatment

4 weeks

Treatment

Participants receive epidural cortical stimulation for treatment-resistant depression

up to 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

7 months

What Are the Treatments Tested in This Trial?

Interventions

• Synergy

Trial Overview The study tests epidural cortical stimulation (ECS), where an electric wire is placed on the brain's surface over the medial prefrontal cortex—a key area in mood regulation. This minimally invasive technique aims to help those with major depressive disorder who haven't improved after trying other treatments.

How Is the Trial Designed?

Group I: Synergy, Epidural cortical stimulation Experimental Treatment 1 Intervention

Epidural cortical stimulation (medial prefrontal cortex) for treatment resistant depression. The primary aim of this pilot study was to assess the feasibility and safety of EpCS in patients with treatment-resistant depression. Ultimately, for EpCS to be found effective, a much larger double blind placebo controlled study would be needed.

Who Is Running the Clinical Trial?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

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

National Alliance for Research on Schizophrenia and Depression

Collaborator

Trials

97

Recruited

4,100+

Published Research Related to This Trial

A retrospective analysis of 157 patients receiving 3,106 electroconvulsive therapy (ECT) applications showed a low incidence of serious and potentially life-threatening adverse events (pLTAEs) at just 0.097%, indicating that ECT is a relatively safe treatment when conducted in a controlled environment.

While minor adverse events were more common with higher stimulus doses and increased treatment frequency, no patients experienced permanent health damage or death, suggesting that ECT can be considered a viable option for treating depression in psychiatric settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk Assessment of Electroconvulsive Therapy in Clinical Routine: A 3-Year Analysis of Life-Threatening Events in More Than 3,000 Treatment Sessions. Hajak, VL., Hajak, G., Ziegelmayer, C., et al.[2021]

Chronic and intermittent epidural prefrontal cortical stimulation (EpCS) was well-tolerated by all five patients with treatment-resistant depression, indicating a favorable safety profile for this new treatment approach.

At a 7-month follow-up, patients showed significant improvements in depression scores, with an average reduction of 54.9% on the Hamilton Rating Scale and 60.1% on the Inventory of Depressive Symptoms, and three patients achieved remission, suggesting promising efficacy for EpCS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bilateral epidural prefrontal cortical stimulation for treatment-resistant depression. Nahas, Z., Anderson, BS., Borckardt, J., et al.[2022]

Subanaesthetic doses of ketamine have shown substantial efficacy in treating depression, with response rates averaging 77% and remission rates around 43% within 4 to 72 hours after a single dose.

Despite the rapid improvement in mood for many patients, the effects are often short-lived, highlighting the need for further research on dosing regimens and strategies to maintain the antidepressant response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine as a new treatment for depression: a review of its efficacy and adverse effects. Katalinic, N., Lai, R., Somogyi, A., et al.[2013]

Cranial electrical stimulation (CES) has been suggested as a treatment for acute depression with minimal adverse effects, but this systematic review found no studies that met the criteria for rigorous evaluation.

The authors concluded that there is a significant lack of methodologically sound research on CES for depression, highlighting the need for more double-blind randomized controlled trials to assess its efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alternating current cranial electrotherapy stimulation (CES) for depression. Kavirajan, HC., Lueck, K., Chuang, K.[2023]

Epidural prefrontal cortical stimulation (EpCS) showed promising long-term efficacy for treatment-resistant depression (TRD) in a study of 5 adults, with 60% of participants remaining in remission after 5 years and significant improvements in depression scores over time.

The therapy was generally well-tolerated, although there were serious adverse events related to device malfunctions and infections, highlighting the need for careful monitoring in patients undergoing this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-Year Follow-Up of Bilateral Epidural Prefrontal Cortical Stimulation for Treatment-Resistant Depression. Williams, NR., Short, EB., Hopkins, T., et al.[2018]

This study presents the first case of safely administering electroconvulsive therapy (ECT) to a patient with deep brain stimulation (DBS) by temporarily interrupting DBS only during the ECT sessions.

Previous reports indicated no adverse events when DBS was withheld for the entire ECT course, but this case suggests that short interruptions during ECT may be a safe approach, warranting further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temporary interruption of deep brain stimulation for Parkinson's disease during outpatient electroconvulsive therapy for major depression: a novel treatment strategy. Ducharme, S., Flaherty, AW., Seiner, SJ., et al.[2011]

Chronic epidural stimulation (EpCS) of the left dorsolateral prefrontal cortex (DLPFC) showed significant improvement in patients with refractory major depressive disorder (MDD), particularly with mixed mode and continuous anodic stimulation, indicating its potential as an effective treatment option.

The study found that optimal electrode placement in the lateral and anterior regions of the DLPFC correlated with the greatest improvement in depression symptoms, suggesting that careful consideration of stimulation parameters is crucial for maximizing therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of electrode location and stimulation polarity in patient response to cortical stimulation for major depressive disorder. Pathak, Y., Kopell, BH., Szabo, A., et al.[2021]

Implanted cortical stimulation, whether epidural or subdural, can provide long-term treatment benefits for neuropsychiatric diseases, especially when transcranial stimulation is ineffective.

While subdural stimulation allows for more precise targeting and lower current use, it carries a higher risk of complications such as seizures and infections compared to epidural stimulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epidural and subdural stimulation. Tronnier, V., Rasche, D.[2013]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2863140/

Bilateral Epidural Prefrontal Cortical Stimulation for Treatment ... Vagus nerve stimulation: 2-year outcomes for bipolar versus unipolar treatment-resistant depression. Biol Psychiatry. 2008;64:455–460. doi: 10.1016/j ...

2. clinicaltrial.be clinicaltrial.be/en/details/13579?per_page=20&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

Epidural Cortical Stimulation for Depression - Clinical T... The primary aim of this pilot study was to assess the feasibility and safety of EpCS in patients with treatment-resistant depression. Ultimately ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1935861X16301917

Five-Year Follow-Up of Bilateral Epidural Prefrontal ... All 5 patients continued to tolerate the therapy. The mean improvements from pre-implant baseline on the HRSD24 were [7 months] 54.9% (±37.7), [1 year] 41.2% ( ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9169472/

A narrative review on invasive brain stimulation for treatment ... Epidural cortical stimulation, an invasive intervention with few reported cases, showed positive results (40-60% response), although more extensive trials are ...

5. frontiersin.org frontiersin.org/journals/human-neuroscience/articles/10.3389/fnhum.2023.1125074/full

Neuromodulation for treatment-resistant depression After 7 months of follow-up, patients experienced significant improvement in depressive symptoms, compared to the pre-implantation baseline—with ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006322309010208

Bilateral Epidural Prefrontal Cortical Stimulation for ... We chose to pilot the safety and therapeutic benefits of chronic and intermittent epidural prefrontal cortical stimulation (EpCS) in patients with treatment- ...

7. journals.lww.com journals.lww.com/neurosurgery/fulltext/2012/01000/unimpressive_efficacy_and_unclear_safety.33.aspx

Unimpressive Efficacy and Unclear Safety Assessment of... The authors stated that no adverse cognitive effects were observed, but detailed reporting of the neuropsychological testing results was not provided. Based on ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4121451/

Deep Brain Stimulation for Treatment-resistant Depression We performed a systematic review of the literature pertaining to DBS for treatment-resistant depression to evaluate the safety and efficacy of this procedure.