Brain Stimulation for Depression

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

Trial Summary

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 data supports the effectiveness of the treatment INTRACALVARIAL PREFRONTAL CORTICAL STIMULATION (IpCS) for depression?

Research on a similar treatment, transcranial direct current stimulation (tDCS), shows it can reduce depression symptoms significantly. Studies found that tDCS applied to the prefrontal cortex led to a notable decrease in depression scores, with improvements seen as early as two weeks into treatment. ^{1 2 3 4 5}

Is intracalvarial prefrontal cortical stimulation (IpCS) safe for humans?

Research on transcranial direct current stimulation (tDCS), a similar non-invasive brain stimulation technique, shows it is generally safe with low and temporary side effects, though some studies report minor skin issues. However, a home-based study was stopped early due to safety concerns, highlighting the need for careful monitoring. ^{4 6 7 8 9}

How is Intracalvarial Prefrontal Cortical Stimulation (IpCS) different from other depression treatments?

Intracalvarial Prefrontal Cortical Stimulation (IpCS) is unique because it involves direct stimulation of the brain's prefrontal cortex, potentially offering a more targeted approach compared to non-invasive methods like transcranial direct current stimulation (tDCS), which uses weak electrical currents applied externally to the scalp. ^{1 3 10 11 12}

What is the purpose of this trial?

This trial tests a new method where an electrode is placed inside the skull to stimulate a brain area involved in mood regulation. It targets patients with severe depression who haven't improved with other treatments. The goal is to see if this method can reduce their depression symptoms. This new treatment option is being scientifically evaluated for patients with major depression who have not responded to conventional treatments.

Research Team

Jon T Willie, MD, PhD

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

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]

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]

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) 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 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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

A Clinical Case Series of Acute and Maintenance Home Administered Transcranial Direct Current Stimulation in Treatment-Resistant Depression. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Home-administered transcranial direct current stimulation is a feasible intervention for depression: an observational cohort study. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation for depression: 3-week, randomised, sham-controlled trial. [2022]

4. Germany 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). [2022]

5. England 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. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Safety of Transcranial Direct Current Stimulation of Frontal, Parietal, and Cerebellar Regions in Fasting Healthy Adults. [2020]

7. Germany 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. [2022]

8. Germany 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. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

A Systematic Review on the Acceptability and Tolerability of Transcranial Direct Current Stimulation Treatment in Neuropsychiatry Trials. [2018]

10. United States pubmed.ncbi.nlm.nih.gov

Treatment of depression with transcranial direct current stimulation (tDCS): a review. [2022]

11. Netherlands pubmed.ncbi.nlm.nih.gov

A pilot study of alternative transcranial direct current stimulation electrode montages for the treatment of major depression. [2018]

12. United States pubmed.ncbi.nlm.nih.gov

Molecular basis and clinical perspectives of deep brain stimulation for major depressive disorder. [2023]