Electrical stimulation for severe treatment-resistant depression
Official title: Prefrontal Cortical Stimulation (PCS) for Severe Treatment Resistant Depression
Run by University of Minnesota · NCT04124341 · Data updated 2026-11-12
This study is testing if a new brain stimulation technique can help people with severe depression that hasn't responded to other treatments feel better.
Quick facts
| Study type | Interventional |
|---|---|
| Ages | 22 Years to 70 Years |
| Sex | All |
| Enrollment | 15 (estimated) |
| Sponsor | University of Minnesota Academic / other |
| Locations | 1 site (Minneapolis, Minnesota) |
| Status | Recruiting |
| Started | September 29, 2021 |
| Main results expected | December 31, 2031 |
| Study ends | December 31, 2032 |
| Registry record updated | September 1, 2026 |
| Trial ID | NCT04124341 on ClinicalTrials.gov |
Is this trial a fit for you?
✓Likely a good fit
Ideal candidates are individuals with chronic depression who have not responded to multiple antidepressant treatments and have undergone or refused electroconvulsive therapy.
✕Probably not a fit
Patients with mild depression or those who have not tried multiple antidepressant treatments may not benefit from this study.
A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.
What this trial studies
This study tests the effectiveness of electrical stimulation applied to the frontal region of the brain to alleviate symptoms of severe treatment-resistant depression. Participants will undergo a surgical procedure to implant leads for bilateral subdural prefrontal cortical stimulation (PCS), using devices approved for other conditions but still investigational for depression. The study consists of multiple stages, including baseline assessments, surgery, acute phase monitoring, and follow-up evaluations to assess the impact of the stimulation on depressive symptoms.
Why it matters
Potential benefit: If successful, this approach could provide a new treatment option for patients suffering from severe depression that has not responded to traditional therapies.
How similar studies have gone: While the use of electrical stimulation for depression is still investigational, similar approaches have shown promise in other studies targeting brain stimulation for various conditions.
Who can join: the full rules
Show full inclusion / exclusion criteria
If diagnosed with Unipolar or Bipolar Type II treatment resistant depression: Inclusion Criteria: * 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 a Medicare program Exclusion Criteria: * 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: 1. Has made a suicide attempt within the previous 12 months that required medical treatment 2. Has made greater than or equal to two suicide attempts in the past 12 months 3. 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 4. 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: Inclusion Criteria: * 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 Exclusion Criteria: * 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: 1. Has made a suicide attempt within the previous 12 months that required medical treatment 2. Has made greater than or equal to two suicide attempts in the past 12 months 3. 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 4. 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
Where it's running
-
University of Minnesota
Minneapolis, Minnesota, United States Recruiting
Study contacts
- Principal investigator: Ziad Nahas, MD — University of Minnesota
- Study coordinator: Ziad Nahas, MD, MSCR
- Email: znahas@umn.edu
- Phone: 952-525-4505
Similar studies
Other studies for the same condition or treatment. Recruiting studies are listed first.
-
EEG-Guided TMS for Adults With Depression
This study tests whether delivering intermittent theta burst stimulation (iTBS) timed to brain waves using EEG can improve treatment for adults with major depressive disorder who have not responded to usual antidepressants.
-
Ketamine plus behavioral activation therapy for treatment-resistant depression
This study tests whether adding behavioral activation therapy to ketamine treatment helps adults with treatment-resistant depression feel better than ketamine alone.
-
Ketamine-assisted psychotherapy for treatment-resistant depression in adults
This open-label program tests intravenous ketamine combined with psychotherapy to see if it helps adults with treatment-resistant depression.
-
Mindfulness‑augmented brain stimulation for treatment‑resistant depression
This trial will test whether combining fast brain stimulation (iTBS) with a digital mindfulness program helps people with treatment‑resistant depression reduce symptoms and improve thinking.
-
ipRGCs as biomarkers to predict TMS response in major depressive disorder
This study tests whether retinal cells called ipRGCs can predict who will respond to TMS in treatment-resistant depression.
-
Rapid, robot-guided TMS with NRX-101 for treatment-resistant depression
This trial tests whether a single-day, robot-guided brain stimulation plus NRX-101 can help adults with treatment-resistant depression compare to sham stimulation and placebo.
How to take part
- Review the eligibility criteria above with your treating physician.
- Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
- Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.