Treatment Resistant DepressionEpCS-DNCT00565617
Epidural Cortical Stimulation for Depression
A study testing Synergy, Epidural cortical stimulation in people with Treatment Resistant Depression, run by Medical University of South Carolina at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 21 to 80 years
- Conditions the study is for
- Treatment Resistant Depression
- What is being tested?
- Synergy, Epidural cortical stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2007to Dec 2028
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- To be eligible for this study, a subject must meet all the following inclusion and exclusion criteria:
- Subject has a diagnosis of chronic (≥ two years) or recurrent (multiple prior episodes) depression and is currently experiencing a major depressive episode without psychotic features as defined by DSM IV criteria.
- Subjects may have a diagnosis or unipolar or bipolar depressive episode.
- Subject has not had an adequate response to 4 or more adequate antidepressant treatments in the current depressive episode according to the Antidepressant Treatment History Form (ATHF) (Sackeim et al 1997).
- Subject must be between the ages of 21 and 80.
- Baseline HDRS 24-item ≥ 20 (both visits 1 week apart)
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- Subject must be able to complete the evaluations needed for this study including the functional imaging scans.
- Subject must have had a history of one successful course of ECT in the past.
- Subject must provide written informed consent.
- Subject is stable on all antidepressant medication for at least 4 weeks before the baseline visit or not be taking antidepressant medication prior to entering the study.
- Subject must be able to remain on current medication schedule for the first 19 weeks of the study.
- Subject is not on a medication known to increase the risk of cortical stimulation-induced seizures. These include theophylline, stimulant medications, bupropion, or supraphysiological doses of thyroid supplements.
Who cannot join
- The presence of any of the following will exclude a subject from the study:
- 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 received general anesthetic within the last 30 days prior to enrollment (not including ECT procedure).
- Subject currently has another investigational device or cardiac pacemaker, implantable defibrillator, or other implantable stimulator
- Subject on anticoagulant drugs, with low platelets counts or have PT or PTT abnormalities or other risk factors for intra-operative or post-operative bleeding
- Subject is expected to require full body magnetic resonance imaging (MRI) during the clinical study.
Show all 11Show fewer
- 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).
- Subject has a history of schizophrenia, schizoaffective disorder, or other psychotic disorder, active substance abuse or dependence (with the exception to caffeine and nicotine abuse) or a current major depressive episode that includes psychotic features (commonly referred to as psychotic depression) according to the DSM IV criteria.
- Subject with a diagnosis of dementia with a Mini-Mental State Exam (MMSE) ≤23.
- Female subjects with a positive urine pregnancy test.
- Subject with a positive urine drug screen or current alcohol or substance abuse other than nicotine and caffeine.
Trial locations and contacts
1 site in 1 country.
United States1 site
Medical University of South Carolina
Charleston, South Carolina, 29403
About this study
Official title: A Pilot Safety and Efficacy Study of Epidural Prefrontal Cortical Stimulation (EpCS) in Severe Treatment Resistant Depression
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.
Read the detailed description
Hypothesis: Severely Treatment Resistant Unipolar Depressed Subjects with EpCS of medial prefrontal cortex will show a significant decrease in depression symptoms at 6 months post-implant when compared to baseline and to a matched control group treated with electroconvulsive therapy (ECT).
Method: We will enroll 5 subjects with severe refractory depression in an open trial with a 1 month placebo lead in, and for up to 1 years. We will also naturalistically follow 5 matched control patients treated with ECT. Depressive and cognitive symptoms will be rated periodically to assess the safety and efficacy of this procedure.
Significance: This study takes advantage of the expertise at MUSC with various neuromodulation technologies to begin answering the crucial role of targeted cortical brain stimulation and its potential role in treatment resistant depression. This is a crucial pilot study that might lead to an entire new class of therapies for depression.
- Conditions
- Treatment Resistant Depression
- Being tested
- Synergy, Epidural cortical stimulation
- Keywords
- depression, epidural, cortical stimulation, brain stimulation, treatment-resistant, deep brain stimulation, TMS, DBS, ECS
- Medical subject headings
- Depressive Disorder, Treatment-Resistant, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Synergy, Epidural cortical stimulationDevice
Also called Epidural cortical stimulation
Epidural cortical stimulation
| Study group | Role | What they receive |
|---|---|---|
| Synergy, Epidural cortical stimulation | Experimental | 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. Receives: Device: Synergy, Epidural cortical stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
HDRS-24 Items
Hamilton Depression Rating Scale (HDRS) is a standard, validated depression rating scale.
It is a 24 item scale, but the primary score is based on the first 17 answers for a total score for depression.
0-7=Normal 8 - 13 = Mild Depression 14-18 = Moderate Depression 19 - 22 = Severe Depression > 23 = Very Severe Depression
Measured: 7 months from baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Nov 2007 (estimated)
- Study startOct 2007
- Primary completionDec 2009
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Treatment Resistant DepressionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- We are currently monitoring participants that were implanted with Epidural Cortical Stimulators starting back in 2008. Primary investigation is completed, but they have implanted devices for investigational treatment of depression. We will keep the study open while they are monitored.
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of South Carolina
- Sponsor type
- University, hospital or other
- Collaborators
- Medtronic, National Alliance for Research on Schizophrenia and Depression
- Responsible party
- Principal investigator, E. Baron Short, Medical University of South Carolina
- Investigators
- Edward B Short, MD, MSCR, Principal investigator, Medical University of South Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00565617
- Sponsor's protocol ID
- HR - 16908
- Acronym
- EpCS-D
- Status last verified
- Apr 2026
- First submitted
- 29 Nov 2007
- Last updated
- 13 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Undecided: We are currently monitoring participants. Primary investigation is completed, but they have implanted devices for investigational treatment of depression. We will keep the study open while they are monitored.
Publications
Nahas Z, Anderson BS, Borckardt J, Arana AB, George MS, Reeves ST, Takacs I. Bilateral epidural prefrontal cortical stimulation for treatment-resistant depression. Biol Psychiatry. 2010 Jan 15;67(2):101-9. doi: 10.1016/j.biopsych.2009.08.021.
PubMed 19819427Williams NR, Short EB, Hopkins T, Bentzley BS, Sahlem GL, Pannu J, Schmidt M, Borckardt JJ, Korte JE, George MS, Takacs I, Nahas Z. Five-Year Follow-Up of Bilateral Epidural Prefrontal Cortical Stimulation for Treatment-Resistant Depression. Brain Stimul. 2016 Nov-Dec;9(6):897-904. doi: 10.1016/j.brs.2016.06.054. Epub 2016 Jun 28.
PubMed 27443912
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Safety and Efficacy Study of Epidural Prefrontal Cortical Stimulation (EpCS) in Severe Treatment Resistant Depression
- ClinicalTrials.gov ID
- NCT00565617
- Acronym / sponsor ID
- EpCS-D / HR - 16908
- Conditions
- Treatment Resistant Depression
- Keywords
- depression, epidural, cortical stimulation, brain stimulation, treatment-resistant, deep brain stimulation, TMS, DBS
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Medical University of South CarolinaUniversity, hospital or other
- Collaborators
- Medtronic, National Alliance for Research on Schizophrenia and Depression
- Study start
- Oct 2007
- Primary completion
- Dec 2009 (actual)
- Study completion
- Dec 2028 (estimated)
- First posted
- 30 Nov 2007 (estimated)
- Results
- Posted 18 Sep 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Hypothesis: Severely Treatment Resistant Unipolar Depressed Subjects with EpCS of medial prefrontal cortex will show a significant decrease in depression symptoms at 6 months post-implant when compared to baseline and to a matched control group treated with electroconvulsive therapy (ECT).
Method: We will enroll 5 subjects with severe refractory depression in an open trial with a 1 month placebo lead in, and for up to 1 years. We will also naturalistically follow 5 matched control patients treated with ECT. Depressive and cognitive symptoms will be rated periodically to assess the safety and efficacy of this procedure.
Significance: This study takes advantage of the expertise at MUSC with various neuromodulation technologies to begin answering the crucial role of targeted cortical brain stimulation and its potential role in treatment resistant depression. This is a crucial pilot study that might lead to an entire new class of therapies for depression.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- We are currently monitoring participants that were implanted with Epidural Cortical Stimulators starting back in 2008. Primary investigation is completed, but they have implanted devices for investigational treatment of depression. We will keep the study open while they are monitored.
| Arm | Type | Receives |
|---|---|---|
| Synergy, Epidural cortical stimulation | Experimental | Device: Synergy, Epidural cortical stimulationEpidural 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 may qualify
- Ages
- 21 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- To be eligible for this study, a subject must meet all the following inclusion and exclusion criteria:
- Subject has a diagnosis of chronic (≥ two years) or recurrent (multiple prior episodes) depression and is currently experiencing a major depressive episode without psychotic features as defined by DSM IV criteria.
- Subjects may have a diagnosis or unipolar or bipolar depressive episode.
- Subject has not had an adequate response to 4 or more adequate antidepressant treatments in the current depressive episode according to the Antidepressant Treatment History Form (ATHF) (Sackeim et al 1997).
- Subject must be between the ages of 21 and 80.
Key exclusion criteria (11 listed)
- 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 received general anesthetic within the last 30 days prior to enrollment (not including ECT procedure).
- Subject currently has another investigational device or cardiac pacemaker, implantable defibrillator, or other implantable stimulator
- Subject on anticoagulant drugs, with low platelets counts or have PT or PTT abnormalities or other risk factors for intra-operative or post-operative bleeding
- Subject is expected to require full body magnetic resonance imaging (MRI) during the clinical study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Synergy, Epidural cortical stimulationAlso: Epidural cortical stimulationEpidural cortical stimulation | Device | Synergy, Epidural cortical stimulation |
Primary outcome
HDRS-24 Items
Time frame: 7 months from baseline
Hamilton Depression Rating Scale (HDRS) is a standard, validated depression rating scale. It is a 24 item scale, but the primary score is based on the first 17 answers for a total score for depression. 0-7=Normal 8 - 13 = Mild Depression 14-18 = Moderate Depression 19 - 22 = Severe Depression > 23 = Very Severe Depression
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 19819427Nahas Z, Anderson BS, Borckardt J, Arana AB, George MS, Reeves ST, Takacs I. Bilateral epidural prefrontal cortical stimulation for treatment-resistant depression. Biol Psychiatry. 2010 Jan 15;67(2):101-9. doi: 10.1016/j.biopsych.2009.08.021.
- Results publication: PubMed 27443912Williams NR, Short EB, Hopkins T, Bentzley BS, Sahlem GL, Pannu J, Schmidt M, Borckardt JJ, Korte JE, George MS, Takacs I, Nahas Z. Five-Year Follow-Up of Bilateral Epidural Prefrontal Cortical Stimulation for Treatment-Resistant Depression. Brain Stimul. 2016 Nov-Dec;9(6):897-904. doi: 10.1016/j.brs.2016.06.054. Epub 2016 Jun 28.
- Brain Stimulation Service / Mood Disorders Program at MUSCLink provided by the sponsor.
- NARSADLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided. We are currently monitoring participants. Primary investigation is completed, but they have implanted devices for investigational treatment of depression. We will keep the study open while they are monitored.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Edward B Short, MD, MSCR principal investigator
Medical University of South Carolina
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Synergy, Epidural cortical stimulation in people with Treatment Resistant Depression, run by Medical University of South Carolina at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 13 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Sep 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
HDRS-24 Items (time frame: 7 months from baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00565617, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2026.