Brain Stimulation for Depression

Recruiting at 1 trial location

Overseen By Arthur Gribetz

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Inner Cosmos Inc

Must not be taking: MAO inhibitors

Disqualifiers: Schizophrenia, Epilepsy, Brain injury, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4 months

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to help people with severe depression that hasn't improved with other treatments. It involves placing a small device inside the skull to gently stimulate a part of the brain linked to mood regulation, known as Intracalvarial Prefrontal Cortical Stimulation (IpCS). The goal is to determine if this can reduce depression symptoms over time. Suitable candidates have struggled with major depression for a long time and haven't found relief from at least two different antidepressants. Participants should also have tried and briefly responded to non-invasive brain stimulation therapies. As an unphased trial, this study offers an opportunity to contribute to groundbreaking research in depression treatment.

Will I have to stop taking my current medications?

You won't have to stop taking your current medications, but you will need to keep them the same for the first four months of the study. After that, you can change your medications if needed.

What prior data suggests that this method is safe for treating depression?

Research shows that a new method called intracalvarial prefrontal cortical stimulation (IpCS) is being tested for safety in people with treatment-resistant depression (TRD). Earlier studies on similar techniques, like bilateral epidural prefrontal cortical stimulation, generally found them to be well-tolerated. Patients experienced some side effects, usually mild, such as headaches and scalp discomfort.

This trial is in an early phase, focusing primarily on assessing the treatment's safety for humans. Reaching this stage suggests that earlier research did not identify major safety issues. Participants should discuss any concerns with the trial team to understand the potential risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for depression, which often include medications like SSRIs or therapies such as cognitive behavioral therapy, Intracalvarial Prefrontal Cortical Stimulation (IpCS) stands out because it directly targets the brain's prefrontal cortex through a neurostimulation device. This method of brain stimulation is designed to potentially provide faster relief from depressive symptoms by directly modulating brain activity, rather than altering neurotransmitter levels over time. Researchers are excited about IpCS because it offers a new mechanism of action, potentially leading to quicker and more effective symptom relief for those who haven't benefited from traditional treatments.

What evidence suggests that intracalvarial prefrontal cortical stimulation is effective for treatment-resistant depression?

Research has shown that intracalvarial prefrontal cortical stimulation (IpCS), which participants in this trial will receive, might help reduce symptoms of depression in people who haven't responded to other treatments. This method involves placing a small device on the brain's surface to stimulate a specific area involved in mood control. Some studies found that this stimulation can significantly improve mood. People who underwent similar treatments reported feeling less depressed. This suggests that IpCS could be a promising option for those who haven't found relief with other treatments. ^{1 3 4 6 7}

Who Is on the Research Team?

Jon T Willie, MD, PhD

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for adults aged 21-80 with severe depression that hasn't improved after trying at least two different types of antidepressants. They must have had some response to non-invasive neurostimulation, not be pregnant or able to become pregnant, and be capable of undergoing brain scans and cognitive tests.

Inclusion Criteria

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)

Subject is between the ages of 21 and 80

Exclusion Criteria

The surgical or medical risk for the patient is too high if they undergo the investigational procedure.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Device Placement and Initial Stimulation

Placement of neurostimulation device and initial stimulation of the prefrontal cortex

1-2 weeks

Treatment

Intermittent activation of intracalvarial cortical stimulation to modulate brain regions

4 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 months

What Are the Treatments Tested in This Trial?

Interventions

• INTRACALVARIAL PREFRONTAL CORTICAL STIMULATION (IpCS)

Trial Overview The study is testing a minimally invasive brain stimulation technique called IpCS on the prefrontal cortex in patients with treatment-resistant depression. Up to 20 participants will receive an electrode implant and their mood will be monitored over a year using the MADRS scale.

How Is the Trial Designed?

Group I: Intervention, Placement of Device & Stimulation Experimental Treatment 1 Intervention

Placement of neurostimulation device \& stimulation of prefrontal cortex target

INTRACALVARIAL PREFRONTAL CORTICAL STIMULATION (IpCS) is already approved in United States for the following indications:

Approved in United States as Intracalvarial Prefrontal Cortical Stimulation for:

• Severe Treatment-Resistant Depression

Who Is Running the Clinical Trial?

Inner Cosmos Inc

Lead Sponsor

Trials

1

Recruited

20+

Washington University School of Medicine

Collaborator

Trials

2,027

Recruited

2,353,000+

Published Research Related to This Trial

Transcranial direct current stimulation (tDCS) is a promising non-invasive treatment for Major Depression Disorder (MDD) that can modulate cortical excitability for hours after stimulation, potentially addressing the underlying dysfunction in brain networks associated with depression.

Recent pilot studies have shown that optimized tDCS protocols may effectively reduce symptoms of depression, but further research is necessary to determine the best stimulation parameters and which patients are most likely to benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of depression with transcranial direct current stimulation (tDCS): a review. Nitsche, MA., Boggio, PS., Fregni, F., et al.[2022]

The study assessed the safety of 1.5-mA transcranial direct current stimulation (tDCS) on 49 fasting healthy individuals during Ramadan, finding no serious adverse events or discomfort during the sessions.

There was no significant difference in side effects between active tDCS and sham stimulation, indicating that the tDCS protocol used is safe for fasting adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Transcranial Direct Current Stimulation of Frontal, Parietal, and Cerebellar Regions in Fasting Healthy Adults. Almousa, A., Alajaji, R., Alaboudi, M., et al.[2020]

A systematic review of 64 studies involving 2262 participants found that transcranial direct current stimulation (tDCS) has a low dropout rate (6% for active and 7.2% for sham), indicating good acceptability among participants.

Despite the low dropout rates, many studies inadequately reported adverse events (AEs), highlighting a need for improved guidelines to standardize AE reporting in tDCS research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review on the Acceptability and Tolerability of Transcranial Direct Current Stimulation Treatment in Neuropsychiatry Trials. Aparício, LVM., Guarienti, F., Razza, LB., et al.[2018]

Transcranial direct current stimulation (tDCS) showed significant antidepressant effects in a study of 64 participants with depression, with improved mood after active treatment compared to sham treatment.

While tDCS was generally safe, there was a cautionary note regarding mood switching in individuals with bipolar disorder, as one participant experienced hypomania after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation for depression: 3-week, randomised, sham-controlled trial. Loo, CK., Alonzo, A., Martin, D., et al.[2022]

The pilot study involving 14 depressed participants found that both alternative electrode montages (Fronto-Occipital and Fronto-Cerebellar) for transcranial direct current stimulation (tDCS) were safe and feasible, with no significant adverse effects reported.

The Fronto-Occipital montage showed a promising mood improvement rate of 43.8% after four weeks, suggesting potential efficacy in treating depression, while the Fronto-Cerebellar montage had a lower improvement rate of 15.9%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study of alternative transcranial direct current stimulation electrode montages for the treatment of major depression. Ho, KA., Bai, S., Martin, D., et al.[2018]

In a case series of 16 treatment-resistant depression patients, home-administered transcranial direct current stimulation (HA-tDCS) showed clinical benefits, with 5 out of 12 patients responding within 6 weeks and 9 maintaining improvements after 12 weeks of treatment.

HA-tDCS was found to be safe and well-tolerated, with no significant cognitive impairments reported over up to 2 years of treatment, although two patients experienced mild side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Clinical Case Series of Acute and Maintenance Home Administered Transcranial Direct Current Stimulation in Treatment-Resistant Depression. Le, B., Alonzo, A., Bull, M., et al.[2023]

The study aims to evaluate the effectiveness of combining cognitive behavioral therapy (CBT) with transcranial direct current stimulation (tDCS) in treating Major Depressive Disorder (MDD) in 192 patients, with assessments at multiple time points over 30 weeks.

This trial will not only measure changes in depression scores but also explore the neurobiological effects of the combined treatment using neuropsychological tests and fMRI, potentially providing insights into how these interventions work together to improve brain function in MDD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PsychotherapyPlus: augmentation of cognitive behavioral therapy (CBT) with prefrontal transcranial direct current stimulation (tDCS) in major depressive disorder-study design and methodology of a multicenter double-blind randomized placebo-controlled trial. Bajbouj, M., Aust, S., Spies, J., et al.[2022]

The DepressionDC trial is a multicenter study involving 152 patients with major depressive disorder (MDD) who have not responded to SSRIs, testing the efficacy and safety of prefrontal transcranial direct current stimulation (tDCS) as an add-on treatment over 6 weeks.

This trial employs a rigorous triple-blind design and advanced monitoring of tDCS parameters, aiming to determine if tDCS can significantly improve depression scores compared to a sham treatment, while also assessing cognitive safety and other psychopathological outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prefrontal transcranial direct current stimulation (tDCS) as treatment for major depression: study design and methodology of a multicenter triple blind randomized placebo controlled trial (DepressionDC). Padberg, F., Kumpf, U., Mansmann, U., et al.[2022]

A randomized controlled trial (HomeDC) on the use of transcranial direct current stimulation (tDCS) at home for major depressive disorder was prematurely terminated due to safety concerns, specifically skin lesions in patients, highlighting the need for better safety monitoring.

Although the study showed significant reductions in depression scales over time, active tDCS did not demonstrate superior efficacy compared to sham tDCS, indicating that further high-quality research is necessary to explore the potential of tDCS for treating depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TDCS at home for depressive disorders: an updated systematic review and lessons learned from a prematurely terminated randomized controlled pilot study. Kumpf, U., Palm, U., Eder, J., et al.[2023]

In a clinical trial involving 16 participants with moderate-to-severe major depression, transcranial direct current stimulation (tDCS) led to a significant reduction in depressive symptoms within just two weeks of treatment, as measured by the Montgomery-Åsberg Depression Rating Scale.

By the end of the treatment and tapering phase, 75% of participants responded positively to the tDCS intervention, with 63% achieving remission, indicating that tDCS can be an effective option for managing major depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Home-administered transcranial direct current stimulation is a feasible intervention for depression: an observational cohort study. Charvet, L., George, A., Charlson, E., et al.[2023]

In a clinical trial with 40 medication-free patients suffering from major depression, transcranial direct current stimulation (tDCS) targeting the left dorsolateral prefrontal cortex (DLPFC) resulted in a significant 40.4% reduction in depression scores, indicating its potential efficacy as a treatment.

The treatment was well tolerated with minimal side effects, and the positive effects on mood persisted for one month after the treatment ended, suggesting that tDCS could be a promising therapeutic option for major depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, double-blind clinical trial on the efficacy of cortical direct current stimulation for the treatment of major depression. Boggio, PS., Rigonatti, SP., Ribeiro, RB., et al.[2022]

Stimulation of the subcallosal cingulate cortex (SCC) through deep brain stimulation (DBS) is a promising and safe alternative for treating treatment-resistant depression, showing significant improvements in 50-60% of patients over 20 years of multicenter studies.

This intervention appears to enhance blood supply and glucose metabolism in the SCC, potentially activating the brain's reward system and leading to a greater sense of well-being and reduced depressive symptoms, with about one-third of patients achieving remission.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular basis and clinical perspectives of deep brain stimulation for major depressive disorder. Teixeira, SA., Moreira, JLS., Sousa, NRT., et al.[2023]

Citations

1. ipl.umn.edu ipl.umn.edu/research-studies/currently-recruiting-studies/prefrontal-cortical-stimulation-pcs-severe-treatment

Prefrontal Cortical Stimulation (PCS) for Severe Treatment ... This research study is designed to test the effectiveness of electrical stimulation on the surface of the brain to treat depressive symptoms.

2. healthymind.wustl.edu healthymind.wustl.edu/items/ipcs/

Ipcs in TRD The purpose of this research study is to look the safety and efficacy of intracalvarial prefrontal cortical stimulation in treatment resistant depressed (TRD) ...

3. withpower.com withpower.com/trial/phase-depressive-disorder-treatment-resistant-5-2022-6e5c2

Brain Stimulation for Depression What data supports the effectiveness of the treatment INTRACALVARIAL PREFRONTAL CORTICAL STIMULATION (IpCS) for depression? Research on a similar treatment ...

4. frontiersin.org frontiersin.org/journals/behavioral-neuroscience/articles/10.3389/fnbeh.2022.893955/full

Transcranial Direct Current Stimulation of the Dorsolateral ... tDCS stimulation of DLPFC could alleviate the clinical symptoms of schizophrenia, depression, drug addiction, attention deficit hyperactivity disorder and ...

5. clinicaltrial.be clinicaltrial.be/nl/details/16869?per_page=100&recruiting=1&enrolling_by_invitation=0&active_not_recruiting=0&not_yet_recruiting=0&completed=0&only_recruiting=1&only_eligible=0

Brain Stimulation for Severe Depression - Klinische Studi... Because of the important role played by the dorsolateral prefrontal cortex in mood regulation, the goal of this study is to apply intracalvarial prefrontal ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2863140/

Bilateral Epidural Prefrontal Cortical Stimulation for Treatment ... Safety and benefits of distance-adjusted prefrontal transcranial ... stimulation: 2-year outcomes for bipolar versus unipolar treatment-resistant depression.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/19819427/

Bilateral epidural prefrontal cortical stimulation for treatment ... We chose to pilot the safety and therapeutic benefits of chronic and intermittent epidural prefrontal cortical stimulation (EpCS) in patients ...