Treatment Resistant DepressionNCT04124341
PCS in Severe Treatment Resistant Depression
A study testing Prefrontal Cortical Stimulation (PCS) in people with Treatment Resistant Depression, run by University of Minnesota at 1 site in United States.
Trial summary
This research study is designed to test if electrical stimulation of the surface of the brain in the frontal region will help treat depressive symptoms. Participants receive intermittent electrical stimulation to the brain, which involves surgically placing electric leads in between the tough fibrous membrane covering… Read more about this study
- Who is it for?
- Ages 22 to 70 years
- Conditions the study is for
- Treatment Resistant Depression
- What is being tested?
- Prefrontal Cortical Stimulation (PCS)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Sep 2021to 31 Dec 2032
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 22 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participant must be able to provide written informed consent.
- Participant has a diagnosis of major depressive episode that is chronic or recurrent as defined by DSM-5 criteria
- Participant has not had an adequate response to four or more adequate antidepressant treatments from at least two different antidepressant treatment categories in the current depressive episode according to the Antidepressant Treatment History Form (ATHF)
- Participant must have had ECT (Electroconvulsive Therapy) or refused to undergo ECT if clinically indicated to them
- Participant must have HRSD greater than or equal to 20 at study entry
- Participant must be able to complete the evaluations needed for this study including the functional imaging scans and the EEG Bayesian optimization sessions
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- Participant must be under the care of a licensed psychiatrist, undergoing regular care evaluations, and inform study team of any change to care team during study participation
- Participant must agree to allow all forms of communication between investigators and study staff and any health care provider (current or having provided service within two years of enrollment)
- Participant must provide name and contact information for at least two people greater than or equal to 22 in age who reside within a 30 minute drive of the participant's residents and whom staff may contact as necessary during study participation
- Participant must be enrolled in a Medicare program
- Participant must be able to provide written informed consent.
- Participant has a diagnosis of major depressive episode that is chronic or recurrent as defined by DSM-5 criteria
- Participant has not had an adequate response to four or more adequate antidepressant treatments from at least two different antidepressant treatment categories in the current depressive episode according to the Antidepressant Treatment History Form (ATHF)
- Participant must have had ECT (Electroconvulsive Therapy) or refused to undergo ECT if clinically indicated to them
- Participant must have HRSD greater than or equal to 20 at study entry
- Participant must be able to complete the evaluations needed for this study including the functional imaging scans and the EEG Bayesian optimization sessions
- Participant must be under the care of a licensed psychiatrist, undergoing regular care evaluations, and inform study team of any change to care team during study participation
- Participant must agree to allow all forms of communication between investigators and study staff and any health care provider (current or having provided service within two years of enrollment)
- Participant must provide name and contact information for at least two people greater than or equal to 22 in age who reside within a 30 minute drive of the participant's residents and whom staff may contact as necessary during study participation
- Participant must be enrolled in an active health insurance plan that will cover the costs associated with standard health care services and injuries
Who cannot join
- The PCS would (in the investigator's judgment) pose an unacceptable surgical or medical risk for the participant
- Participant is unable to undergo required full body magnetic resonance imaging (MRI) during the clinical study
- Participant is judged by the investigator to be acutely suicidal (e.g. within the 30 days prior to the PCS implant the participant has made a suicide attempt or gesture or has made specific plans or preparation to commit suicide or scores 21 or higher on the MSSI)
- In addition to the acute suicidal risks mentioned above, participant meets any of the following:
- Has made a suicide attempt within the previous 12 months that required medical treatment
- Has made greater than or equal to two suicide attempts in the past 12 months
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- Has a clear-cut plan for suicide that states that she/he cannot guarantee that she/he will call her/his regular psychiatrist or the Investigator if the impulse to implement the plan becomes substantial during the study
- Is likely to attempt suicide within the next six months, in the Investigator's opinion
- Participant has a history of schizophrenia, schizoaffective disorder, or other psychotic disorder, or a current major depressive episode that includes psychotic features (commonly referred to as psychotic depression) according to the DSM V criteria
- Participant with a diagnosis of dementia with a Mini-Mental State Exam (MMSE) less than or equal to 23
- Participant with a positive urine pregnancy test
- Participant with a positive urine drug screen
- Participant with DBS (Deep Brain Stimulator)
- Participant with VNS (Vagus Nerve Stimulator) if the device was active in the last 6 months prior to study enrollment
- Participant with history of seizures
- Participant determined by surgical safety committee to have cerebral atrophy, neurodegenerative or neurovascular disease due to age or medical condition that would prohibit optimal surgical safety, per clinical MRI
- If diagnosed with Bipolar Type I treatment resistant depression:
- The PCS would (in the investigator's judgment) pose an unacceptable surgical or medical risk for the participant
- Participant is unable to undergo required full body magnetic resonance imaging (MRI) during the clinical study
- Participant is judged by the investigator to be acutely suicidal (e.g. within the 30 days prior to the PCS implant the participant has made a suicide attempt or gesture or has made specific plans or preparation to commit suicide or scores 21 or higher on the MSSI)
- In addition to the acute suicidal risks mentioned above, participant meets any of the following:
- Has made a suicide attempt within the previous 12 months that required medical treatment
- Has made greater than or equal to two suicide attempts in the past 12 months
- Has a clear-cut plan for suicide that states that she/he cannot guarantee that she/he will call her/his regular psychiatrist or the Investigator if the impulse to implement the plan becomes substantial during the study
- Is likely to attempt suicide within the next six months, in the Investigator's opinion
- Participant has a history of schizophrenia, schizoaffective disorder, or other psychotic disorder, or a current major depressive episode that includes psychotic features (commonly referred to as psychotic depression) according to the DSM V criteria
- Participant with a diagnosis of dementia with a Mini-Mental State Exam (MMSE) less than or equal to 23
- Participant with a positive urine pregnancy test
- Participant with a positive urine drug screen
- Participant with DBS (Deep Brain Stimulator)
- Participant with VNS (Vagus Nerve Stimulator) if the device was active in the last 6 months prior to study enrollment
- Participant with history of seizures
- Participant determined by surgical safety committee to have cerebral atrophy, neurodegenerative or neurovascular disease due to age or medical condition that would prohibit optimal surgical safety, per clinical MRI
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Minnesota
Minneapolis, Minnesota, 55455
Ziad Nahas, MD, MSCR
Rachel Johnson, PhD, 952-525-4505, ipl@umn.edu
About this study
Official title: Prefrontal Cortical Stimulation (PCS) for Severe Treatment Resistant Depression
This research study is designed to test if electrical stimulation of the surface of the brain in the frontal region will help treat depressive symptoms. Participants receive intermittent electrical stimulation to the brain, which involves surgically placing electric leads in between the tough fibrous membrane covering the surface of the brain and the surface of the brain itself. This type of stimulation is referred to as bilateral subdural prefrontal cortical stimulation (PCS) because it will specifically target the outer layer of the brain at the midline, right behind the forehead. It uses a pacemaker-like device, the Proclaim Elite SCS System (non-rechargeable) or the Eterna SCS System (rechargeable), both by Abbott Laboratories for stimulation.
Although the U.S. Food and Drug Administration (FDA) has approved the Proclaim Elite SCS system for brain stimulation for patients with chronic pain and muscular diseases, such as Parkinson's, its use is still investigational, and the surgery is still experimental for patients who have depression.
Read the detailed description
This study has five distinct stages.
Stage 1: Baseline Assessments There is a 14-day baseline period to determine eligibility, including medical history, physical and neurological examinations, and medical test including EKG, blood work, pregnancy test, depression assessments and cognitive assessments. An MRI will also be done prior to implant in order to help the surgeon determine where best to place the leads.
Stage 2: Surgery If deemed to be medically eligible, participants will be hospitalized for a minimum of 3 days, during which they will undergo surgery to implant the device and leads. There will be testing of the leads to explore optimal testing parameters. According to the surgeon's judgment, participants may or may not receive stimulation for 3 weeks following surgery.
Stage 3: Acute phase (19 weeks) Following implantation, participants undergo a CT scan to ensure proper implantation. Later, participants complete 10 follow up visits where assessments of symptoms will be made. Additionally, the first visit will consist of the investigator programming the stimulator while participants watch various photographs with different emotional content and have their brain electrical activity recorded. This will help the investigator choose the best settings for treatment. Pregnancy tests will be done as appropriate.
Stage 4: Follow up (7 months) All participants who complete stage 3 will be offered continued treatment. Participants complete 7 monthly follow-up visits where assessments of symptoms are made. Pregnancy tests will be done as appropriate.
Stage 5: Long Term Follow up (4 years) All participants who complete stage 4 will be offered continued treatment. Participants complete follow up visits every three months, alternating between in person and over zoom. Assessments of symptoms are made. Pregnancy tests will be done as appropriate.
Objectives To demonstrate that PCS causes meaningful and sustained antidepressant response.
To demonstrate that precision functional mapping can identify individualized depression patterns which will lead to personalized maps for targeting the stimulation for an individual.
To establish safe parameters for PCS that do not generate after discharge seizures.
- Conditions
- Treatment Resistant Depression
- Being tested
- Prefrontal Cortical Stimulation (PCS)
- Keywords
- depression, treatment resistant depression, neuromodulation, neuroimaging, precision functional mapping
- 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.
Prefrontal Cortical Stimulation (PCS)Device
Prior to surgery, participants will undergo a high resolution structural scan to identify anatomical landmarks for rostral anterior and lateral prefrontal cortex. Following identification of target areas, PCS quad leads will be surgically projected over the anterior and lateral prefrontal cortex. Participants will be kept in the hospital for a minimum of 72 hours for observation during which the investigators will obtain a high resolution spiral CT scan without contrast to confirm lead placements post-operatively and rule out any intra-cranial bleeds. Patients will receive analgesics which they may continue as an outpatient on as needed basis. During this 2-3 weeks recovery period, the attention to pain control and mood is critical. The research team will contact patients at least twice per week to check on their status.
| Study group | Role | What they receive |
|---|---|---|
| Prefrontal Cortical Stimulation (PCS) | Experimental | Stereotactically implanted bilateral PCS Receives: Device: Prefrontal Cortical Stimulation (PCS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in HRSD Scores
Determine clinical change in depressive symptoms over first year of treatment
Measured: 12 months
Secondary outcomes (1)
Change in HRSD Scores
Determine whether clinical effects seen within the first year persist, improve, or worsen during an extended period of time
Measured: 60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Oct 2019
- Study start29 Sep 2021
- Primary completion31 Dec 2031 (estimated)
- Study completion31 Dec 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ziad Nahas, MD, Principal investigator, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04124341
- Sponsor's protocol ID
- PSYCH-2019-27331
- Status last verified
- Aug 2026
- First submitted
- 10 Oct 2019
- Last updated
- 1 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prefrontal Cortical Stimulation (PCS) for Severe Treatment Resistant Depression
- ClinicalTrials.gov ID
- NCT04124341
- Acronym / sponsor ID
- PSYCH-2019-27331
- Conditions
- Treatment Resistant Depression
- Keywords
- depression, treatment resistant depression, neuromodulation, neuroimaging, precision functional mapping
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- University of MinnesotaUniversity, hospital or other
- Study start
- 29 Sep 2021 (actual)
- Primary completion
- 31 Dec 2031 (estimated)
- Study completion
- 31 Dec 2032 (estimated)
- First posted
- 11 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research study is designed to test if electrical stimulation of the surface of the brain in the frontal region will help treat depressive symptoms. Participants receive intermittent electrical stimulation to the brain, which involves surgically placing electric leads in between the tough fibrous membrane covering the surface of the brain and the surface of the brain itself. This type of stimulation is referred to as bilateral subdural prefrontal cortical stimulation (PCS) because it will specifically target the outer layer of the brain at the midline, right behind the forehead. It uses a pacemaker-like device, the Proclaim Elite SCS System (non-rechargeable) or the Eterna SCS System (rechargeable), both by Abbott Laboratories for stimulation.
Although the U.S. Food and Drug Administration (FDA) has approved the Proclaim Elite SCS system for brain stimulation for patients with chronic pain and muscular diseases, such as Parkinson's, its use is still investigational, and the surgery is still experimental for patients who have depression.
Detailed description
This study has five distinct stages.
Stage 1: Baseline Assessments There is a 14-day baseline period to determine eligibility, including medical history, physical and neurological examinations, and medical test including EKG, blood work, pregnancy test, depression assessments and cognitive assessments. An MRI will also be done prior to implant in order to help the surgeon determine where best to place the leads.
Stage 2: Surgery If deemed to be medically eligible, participants will be hospitalized for a minimum of 3 days, during which they will undergo surgery to implant the device and leads. There will be testing of the leads to explore optimal testing parameters. According to the surgeon's judgment, participants may or may not receive stimulation for 3 weeks following surgery.
Stage 3: Acute phase (19 weeks) Following implantation, participants undergo a CT scan to ensure proper implantation. Later, participants complete 10 follow up visits where assessments of symptoms will be made. Additionally, the first visit will consist of the investigator programming the stimulator while participants watch various photographs with different emotional content and have their brain electrical activity recorded. This will help the investigator choose the best settings for treatment. Pregnancy tests will be done as appropriate.
Stage 4: Follow up (7 months) All participants who complete stage 3 will be offered continued treatment. Participants complete 7 monthly follow-up visits where assessments of symptoms are made. Pregnancy tests will be done as appropriate.
Stage 5: Long Term Follow up (4 years) All participants who complete stage 4 will be offered continued treatment. Participants complete follow up visits every three months, alternating between in person and over zoom. Assessments of symptoms are made. Pregnancy tests will be done as appropriate.
Objectives To demonstrate that PCS causes meaningful and sustained antidepressant response.
To demonstrate that precision functional mapping can identify individualized depression patterns which will lead to personalized maps for targeting the stimulation for an individual.
To establish safe parameters for PCS that do not generate after discharge seizures.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Prefrontal Cortical Stimulation (PCS) | Experimental | Device: Prefrontal Cortical Stimulation (PCS)Stereotactically implanted bilateral PCS |
Who may qualify
- Ages
- 22 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Participant must be able to provide written informed consent.
- Participant has a diagnosis of major depressive episode that is chronic or recurrent as defined by DSM-5 criteria
- Participant has not had an adequate response to four or more adequate antidepressant treatments from at least two different antidepressant treatment categories in the current depressive episode according to the Antidepressant Treatment History Form (ATHF)
- Participant must have had ECT (Electroconvulsive Therapy) or refused to undergo ECT if clinically indicated to them
- Participant must have HRSD greater than or equal to 20 at study entry
Key exclusion criteria (33 listed)
- The PCS would (in the investigator's judgment) pose an unacceptable surgical or medical risk for the participant
- Participant is unable to undergo required full body magnetic resonance imaging (MRI) during the clinical study
- Participant is judged by the investigator to be acutely suicidal (e.g. within the 30 days prior to the PCS implant the participant has made a suicide attempt or gesture or has made specific plans or preparation to commit suicide or scores 21 or higher on the MSSI)
- In addition to the acute suicidal risks mentioned above, participant meets any of the following:
- Participant has a history of schizophrenia, schizoaffective disorder, or other psychotic disorder, or a current major depressive episode that includes psychotic features (commonly referred to as psychotic depression) according to the DSM V criteria
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 |
|---|---|---|
| Prefrontal Cortical Stimulation (PCS)Prior to surgery, participants will undergo a high resolution structural scan to identify anatomical landmarks for rostral anterior and lateral prefrontal cortex. Following identification of target areas, PCS quad leads will be surgically projected over the anterior and lateral prefrontal cortex. Participants will be kept in the hospital for a minimum of 72 hours for observation during which the investigators will obtain a high resolution spiral CT scan without contrast to confirm lead placements post-operatively and rule out any intra-cranial bleeds. Patients will receive analgesics which they may continue as an outpatient on as needed basis. During this 2-3 weeks recovery period, the attention to pain control and mood is critical. The research team will contact patients at least twice per week to check on their status. | Device | Prefrontal Cortical Stimulation (PCS) |
Primary outcome
Change in HRSD Scores
Time frame: 12 months
Determine clinical change in depressive symptoms over first year of treatment
1 secondary outcome
Change in HRSD Scores
Time frame: 60 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2026.
- Individual participant dataSharing planned: No
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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.
Ziad Nahas, MD principal investigator
University of Minnesota
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Prefrontal Cortical Stimulation (PCS) in people with Treatment Resistant Depression, run by University of Minnesota 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 20 inclusion and 33 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: looking for participants now, as of the sponsor's last update on 1 Sep 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ziad Nahas, MD, MSCR (952-525-4505, znahas@umn.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in HRSD Scores (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 1 Sep 2026.