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

5 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Objective: Chronic epidural cortical stimulation (ECS) involves the neurosurgical placement of an electric wire on the surface of the brain with intermittent activation. Over time, ECS modulates local and distal connected brain regions. It is being currently applied over the motor cortex to treat intractable pain. Because of the important role played by the medial prefrontal cortex in mood regulation, the goal of this study is to apply this minimally invasive neurostimulation modality over medial prefrontal cortex in severely ill depressed subjects who have failed all other attempts at treatment.

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.

Is epidural cortical stimulation for depression safe for humans?

There is no specific safety data available for epidural cortical stimulation for depression in the provided research articles. ^{1 2 3 4 5}

How is the treatment Synergy different from other treatments for depression?

Synergy involves epidural cortical stimulation, a unique approach where electrodes are placed on the surface of the brain to deliver electrical impulses, targeting specific brain regions involved in mood regulation. This method is distinct from traditional treatments like medication or talk therapy, as it directly modulates brain activity and is particularly used for treatment-resistant depression. ^{6 7 8 9 10}

What data supports the effectiveness of the treatment Synergy in the clinical trial for Epidural Cortical Stimulation for Depression?

Research shows that epidural cortical stimulation, particularly in the prefrontal cortex, has been effective in treating depression that doesn't respond to other treatments. This type of stimulation has also been used successfully for other conditions like chronic pain and movement disorders, suggesting its potential effectiveness for depression. ^{6 7 8 9 10}

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 haven't improved after 4 or more depression treatments.

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

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

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]

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]

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]

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]

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]

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]

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]

Citations

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

Five-Year Follow-Up of Bilateral Epidural Prefrontal Cortical Stimulation for Treatment-Resistant Depression. [2018]

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

Bilateral epidural prefrontal cortical stimulation for treatment-resistant depression. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Effects of stimulation parameters and electrode location on thresholds for epidural stimulation of cat motor cortex. [2011]

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

The role of electrode location and stimulation polarity in patient response to cortical stimulation for major depressive disorder. [2021]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Epidural and subdural stimulation. [2013]

6. England pubmed.ncbi.nlm.nih.gov

Alternating current cranial electrotherapy stimulation (CES) for depression. [2023]

7. Switzerland 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. [2021]

8. Germany pubmed.ncbi.nlm.nih.gov

[Current use of ECT in the treatment of depressive disorders]. [2018]

9. United States 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. [2011]

10. England pubmed.ncbi.nlm.nih.gov

Ketamine as a new treatment for depression: a review of its efficacy and adverse effects. [2013]