Depression SevereNCT05393622
Brain Stimulation for Severe Depression
A study testing INTRACALVARIAL PREFRONTAL CORTICAL STIMULATION (IpCS) IN SEVERE TREATMENT-RESISTANT DEPRESSION in people with Depression Severe, run by Inner Cosmos Inc at 2 sites in United States.
Trial summary
Chronic intracalvarial cortical stimulation is a minimally invasive method involving the neurosurgical placement of an electrode above the inner table of the skull. Over time, intracalvarial cortical stimulation is intermittently activated to modulate locally and distally connected brain regions. Read more about this study
- Who is it for?
- Ages 21 to 80 years
- Conditions the study is for
- Depression Severe
- What is being tested?
- INTRACALVARIAL PREFRONTAL CORTICAL STIMULATION (IpCS) IN SEVERE TREATMENT-RESISTANT DEPRESSION
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 2 sitesUnited States
- Study dates
- 28 Jul 2022to Dec 2027
- 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 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:
- Subject has a diagnosis of chronic (≥ two years) or recurrent (multiple prior episodes) depression and is currently experiencing a major depressive episode as defined by DSM V criteria.
- Subject meets a pre-treatment baseline threshold with MADRS score of >/=20
- Subject has not had an sustained response to two or more adequately dosed antidepressant treatments from at least two different antidepressant treatment classes in the current depressive episode according to the Antidepressant Treatment History Form (ATHF) (Gaynes, 2020).
- The subject has completed all baseline testing to determine eligibility for the implant surgery (approximately 3 \& 2 weeks prior to expected date for implant surgery, CT \& MRI brain scans and cognitive testing).
- Female subject is not pregnant, agrees to use adequate birth control, or is not capable of becoming pregnant (e.g. post-menopausal, no uterus, ligation of fallopian tubes, surgical removal of ovaries)
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- Subject is between the ages of 21 and 80.
- Subject is able to complete the evaluations needed for this study including the high resolution CT and MRI brain imaging scans.
- Subject is able to provide written informed consent and has signed the consent form for participation in this study.
Who cannot join
- The presence of any of the following will exclude a subject from the study:
- The IpCS would (in the investigator's judgment) pose an unacceptable surgical or medical risk for the patient.
- Subject is expected to require full body magnetic resonance imaging (MRI) during the clinical study.
- Subject is judged by the investigator to be acutely suicidal (e.g., within the 30 days prior to the IpCS 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, or a current major depressive episode that includes psychotic features (commonly referred to as psychotic depression) according to the DSM V criteria.
- Subject has a neurological disorder like Epilepsy, Dementia, Delirium, Amnestic disorder, and cognitive impairment.
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- Subject has a history of brain injury that resulted in cognitive impairment.
- Subject has history of bony disorders (changes in bone density may impact the safe and effective use of the device as well a device implantation).
- Female subjects with a positive urine pregnancy test.
- Subject is taking a MAO inhibitor drug e.g., Isocarboxazid (Marplan), Phenelzine (Nardil), Selegiline (Emsam), or Tranylcypromine (Panate) that may pose risk for general anesthesia. The Coordinator will Identify MAOI drug and discuss with PI.
- Subject and/or Subject's psychiatrist DISAGREES with holding constant the subject's ongoing pharmacotherapy for 4 months following enrollment.
- Presence of hyperostosis frontalis interna (operationally defined, frontal bone thickening of >20mm), as determined by CT scan of the head, at the proposed site of the electrode implantation
- 5.3 Prohibited Therapy During Study Period No drug is prohibited, with the exception of Monoamine oxidase inhibitors (MAOIs) if they are posing a risk for general anesthesia. If a subject presents on a MAOI, this will be brought to the PI's attention for discussion with the anesthesiologist. Subjects will follow study protocol of IpCS-D. In brief, after enrolling in the IpCS-D study, all subjects will have their ongoing pharmacotherapy held constant for four months. After the 4 months, all drugs for treating mood disorders are allowed.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Not yet recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
Darin Dougherty, MD, 617-724-6143, ddougherty@mgb.org
- Recruiting
Washington University in St Louis School of Medicine
St Louis, Missouri, 63110
Karen Flavin, RN, 314 747 6998, karen.flavin@wustl.edu
About this study
Official title: Intracalvarial Prefrontal Cortical Stimulation in Treatment-Resistant Depression
Chronic intracalvarial cortical stimulation is a minimally invasive method involving the neurosurgical placement of an electrode above the inner table of the skull. Over time, intracalvarial cortical stimulation is intermittently activated to modulate locally and distally connected brain regions. Because of the important role played by the dorsolateral prefrontal cortex in mood regulation, the goal of this study is to apply intracalvarial prefrontal cortical stimulation (IpCS) over the dorsolateral prefrontal cortex in severely treatment-resistant depressed (TRD) patients. Per the DSM-V and Centre for Medicare and Medicaid Services (CMS) nomenclatures, TRD patients are commonly defined as those whose treatment failed to produce response or remission after 2 or more attempts of sufficient duration and treatment dose.
In the investigator's study, eligible TRD subjects will have a diagnosis of major depressive disorder with a suboptimal response to an adequate dose and duration of at least two different antidepressant treatment categories. These subjects will also have had exposure and transiently (non-durably) responded to non-invasive neurostimulation. The investigator anticipates that severely Treatment Resistant Depressed (TRD) Subjects with IpCS of the dorsolateral prefrontal cortex will show a significant decrease in depression symptoms as measured by the Montgomery-Asberg Depression Rating Scale (MADRS) at four months post-implant when compared to baseline.
The investigator will enroll up to 20 subjects with severe refractory depression in an open trial, followed for up to one year. Depressive and cognitive symptoms will be rated periodically to assess the safety and efficacy of this procedure.
- Conditions
- Depression Severe
- Being tested
- INTRACALVARIAL PREFRONTAL CORTICAL STIMULATION (IpCS) IN SEVERE TREATMENT-RESISTANT DEPRESSION
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
INTRACALVARIAL PREFRONTAL CORTICAL STIMULATION (IpCS) IN SEVERE TREATMENT-RESISTANT DEPRESSIONDevice
Subjects will have the neurostimulation device placed in the skull and continuous stimulation will be applied to relieve symptoms of depression.
| Study group | Role | What they receive |
|---|---|---|
| Intervention, Placement of Device & Stimulation | Experimental | Placement of neurostimulation device \& stimulation of prefrontal cortex target Receives: Device: INTRACALVARIAL PREFRONTAL CORTICAL STIMULATION (IpCS) IN SEVERE TREATMENT-RESISTANT DEPRESSION |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in depression symptoms
Endpoints for depression will be response and remittance, assessed by Montgomery Asberg Scale for Depression.The minimum and maximum values of the Montgomery Asberg Scale for Depression are ___0___ and ___60__. A higher value means more severe depression.
Measured: 12 months
Secondary outcomes (1)
Change in cognitive function
Endpoints for cognitive remediation will be global cognitive performance, measured by the National Institutes of Health Cognition Battery. The minimum and maximum values of the National Institutes of Health Cognition Battery are __0___ and __40__. A higher value means a better outcome.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2022
- Study start28 Jul 2022
- Primary completionDec 2026 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Depression SevereStudies 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
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Inner Cosmos Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Eric Lenze, MD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05393622
- Sponsor's protocol ID
- G210101
- Status last verified
- Apr 2026
- First submitted
- 23 May 2022
- Last updated
- 15 Apr 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 15 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intracalvarial Prefrontal Cortical Stimulation in Treatment-Resistant Depression
- ClinicalTrials.gov ID
- NCT05393622
- Acronym / sponsor ID
- G210101
- Conditions
- Depression Severe
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Inner Cosmos IncIndustry (pharma, biotech, devices)
- Collaborators
- Washington University School of Medicine, Massachusetts General Hospital
- Study start
- 28 Jul 2022 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 26 May 2022 (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.
Chronic intracalvarial cortical stimulation is a minimally invasive method involving the neurosurgical placement of an electrode above the inner table of the skull. Over time, intracalvarial cortical stimulation is intermittently activated to modulate locally and distally connected brain regions. Because of the important role played by the dorsolateral prefrontal cortex in mood regulation, the goal of this study is to apply intracalvarial prefrontal cortical stimulation (IpCS) over the dorsolateral prefrontal cortex in severely treatment-resistant depressed (TRD) patients. Per the DSM-V and Centre for Medicare and Medicaid Services (CMS) nomenclatures, TRD patients are commonly defined as those whose treatment failed to produce response or remission after 2 or more attempts of sufficient duration and treatment dose.
In the investigator's study, eligible TRD subjects will have a diagnosis of major depressive disorder with a suboptimal response to an adequate dose and duration of at least two different antidepressant treatment categories. These subjects will also have had exposure and transiently (non-durably) responded to non-invasive neurostimulation. The investigator anticipates that severely Treatment Resistant Depressed (TRD) Subjects with IpCS of the dorsolateral prefrontal cortex will show a significant decrease in depression symptoms as measured by the Montgomery-Asberg Depression Rating Scale (MADRS) at four months post-implant when compared to baseline.
The investigator will enroll up to 20 subjects with severe refractory depression in an open trial, followed for up to one year. Depressive and cognitive symptoms will be rated periodically to assess the safety and efficacy of this procedure.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intervention, Placement of Device & Stimulation | Experimental | Device: INTRACALVARIAL PREFRONTAL CORTICAL STIMULATION (IpCS) IN SEVERE TREATMENT-RESISTANT DEPRESSIONPlacement of neurostimulation device \& stimulation of prefrontal cortex target |
Who may qualify
- Ages
- 21 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Subject has a diagnosis of chronic (≥ two years) or recurrent (multiple prior episodes) depression and is currently experiencing a major depressive episode as defined by DSM V criteria.
- Subject meets a pre-treatment baseline threshold with MADRS score of >/=20
- Subject has not had an sustained response to two or more adequately dosed antidepressant treatments from at least two different antidepressant treatment classes in the current depressive episode according to the Antidepressant Treatment History Form (ATHF) (Gaynes, 2020).
- The subject has completed all baseline testing to determine eligibility for the implant surgery (approximately 3 \& 2 weeks prior to expected date for implant surgery, CT \& MRI brain scans and cognitive testing).
- Female subject is not pregnant, agrees to use adequate birth control, or is not capable of becoming pregnant (e.g. post-menopausal, no uterus, ligation of fallopian tubes, surgical removal of ovaries)
Key exclusion criteria (13 listed)
- The IpCS would (in the investigator's judgment) pose an unacceptable surgical or medical risk for the patient.
- Subject is expected to require full body magnetic resonance imaging (MRI) during the clinical study.
- Subject is judged by the investigator to be acutely suicidal (e.g., within the 30 days prior to the IpCS 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, or a current major depressive episode that includes psychotic features (commonly referred to as psychotic depression) according to the DSM V criteria.
- Subject has a neurological disorder like Epilepsy, Dementia, Delirium, Amnestic disorder, and cognitive impairment.
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 |
|---|---|---|
| INTRACALVARIAL PREFRONTAL CORTICAL STIMULATION (IpCS) IN SEVERE TREATMENT-RESISTANT DEPRESSIONSubjects will have the neurostimulation device placed in the skull and continuous stimulation will be applied to relieve symptoms of depression. | Device | Intervention, Placement of Device & Stimulation |
Primary outcome
Change in depression symptoms
Time frame: 12 months
Endpoints for depression will be response and remittance, assessed by Montgomery Asberg Scale for Depression.The minimum and maximum values of the Montgomery Asberg Scale for Depression are ___0___ and ___60__. A higher value means more severe depression.
1 secondary outcome
Change in cognitive function
Time frame: 12 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 15 Apr 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.
Eric Lenze, MD principal investigator
Washington University School of Medicine
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing INTRACALVARIAL PREFRONTAL CORTICAL STIMULATION (IpCS) IN SEVERE TREATMENT-RESISTANT DEPRESSION in people with Depression Severe, run by Inner Cosmos Inc at 2 sites 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 9 inclusion and 13 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 15 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 2 sites 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 Arthur Gribetz (+1 917 732 2102, arthur@innercosmos.io), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in depression symptoms (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 15 Apr 2026.