Trial Summary
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.
What safety data exists for brain stimulation treatment for depression?The safety data for brain stimulation treatment, specifically transcranial direct current stimulation (tDCS), indicates that it is generally considered safe with low and transient adverse events. Studies have shown that tDCS applied to the prefrontal cortex is safe in both healthy individuals and patients with major depressive disorder (MDD). However, a trial on home-based tDCS was prematurely terminated due to safety concerns related to skin lesions, highlighting the need for adequate safety monitoring. Overall, tDCS is seen as a promising treatment for depression, but further high-quality research is needed to address safety issues, especially in home settings.567811
Is Intracalvarial Prefrontal Cortical Stimulation (IpCS) a promising treatment for depression?Yes, Intracalvarial Prefrontal Cortical Stimulation (IpCS) is considered a promising treatment for depression. Similar brain stimulation techniques, like transcranial direct current stimulation (tDCS), have shown potential in reducing depressive symptoms by altering brain activity. These methods are non-invasive and have been optimized over the years, showing promise in early studies.234910
Do I need to stop my current medications for the trial?You don't need to stop your current medications, but you must keep them constant for four months during the trial. If you're taking MAO inhibitors, discuss with the trial team as they may pose a risk for anesthesia.
What data supports the idea that Brain Stimulation for Depression is an effective treatment?The available research shows that transcranial direct current stimulation (tDCS), a type of brain stimulation, is effective in treating depression. In one study, participants with major depression experienced a significant reduction in depressive symptoms after just two weeks of treatment, with 75% responding positively and 63% achieving remission by the end of the treatment period. Another study found that tDCS led to a 40.4% reduction in depression scores, which was significantly better than the placebo group. These findings suggest that tDCS can be a promising treatment for depression, especially for those who have not responded to traditional medications.1361012
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.Treatment Details
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.
1Treatment groups
Experimental Treatment
Group I: Intervention, Placement of Device & StimulationExperimental Treatment1 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
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Research locations nearbySelect from list below to view details:
Washington University in St Louis School of MedicineSaint Louis, MO
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Who is running the clinical trial?
Inner Cosmos IncLead Sponsor
Washington University School of MedicineCollaborator
References
A randomized, double-blind clinical trial on the efficacy of cortical direct current stimulation for the treatment of major depression. [2022]Preliminary findings suggest that transcranial direct current stimulation (tDCS) can have antidepressant effects. We sought to test this further in a parallel-group, double-blind clinical trial with 40 patients with major depression, medication-free randomized into three groups of treatment: anodal tDCS of the left dorsolateral prefrontal cortex (active group - 'DLPFC'); anodal tDCS of the occipital cortex (active control group - 'occipital') and sham tDCS (placebo control group - 'sham'). tDCS was applied for 10 sessions during a 2-wk period. Mood was evaluated by a blinded rater using the Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory (BDI). The treatment was well tolerated with minimal side-effects that were distributed equally across all treatment groups. We found significantly larger reductions in depression scores after DLPFC tDCS [HDRS reduction of 40.4% (+/-25.8%)] compared to occipital [HDRS reduction of 21.3% (+/-12.9%)] and sham tDCS [HDRS reduction of 10.4% (+/-36.6%)]. The beneficial effects of tDCS in the DLPFC group persisted for 1 month after the end of treatment. Our findings support further investigation on the effects of this novel potential therapeutic approach - tDCS - for the treatment of major depression.
Treatment of depression with transcranial direct current stimulation (tDCS): a review. [2022]Major Depression Disorder (MDD) is usually accompanied by alterations of cortical activity and excitability, especially in prefrontal areas. These are reflections of a dysfunction in a distributed cortico-subcortical, bihemispheric network. Therefore it is reasonable to hypothesize that altering this pathological state with techniques of brain stimulation may offer a therapeutic target. Besides repetitive transcranial magnetic stimulation, tonic stimulation with weak direct currents (tDCS) modulates cortical excitability for hours after the end of stimulation, thus, it is a promising non-invasive therapeutic option. Early studies from the 1960s suggested some efficacy of DC stimulation to reduce symptoms in depression, but mixed results and development of psychotropic drugs resulted in an early abandonment of this technique. In the last years tDCS protocols have been optimized. Application of the newly developed stimulation protocols in patients with major depression has shown promise in few pilot studies. Further studies are needed to identify the optimal parameters of stimulation and the clinical and patient characteristics that may condition response to tDCS.
Transcranial direct current stimulation for depression: 3-week, randomised, sham-controlled trial. [2022]Preliminary evidence suggests transcranial direct current stimulation (tDCS) has antidepressant efficacy.
A pilot study of alternative transcranial direct current stimulation electrode montages for the treatment of major depression. [2018]Typically, transcranial direct current stimulation (tDCS) treatments for depression have used bifrontal montages with anodal (excitatory) stimulation targeting the left dorsolateral prefrontal cortex (DLPFC). There is limited research examining the effects of alternative electrode montages.
A Systematic Review on the Acceptability and Tolerability of Transcranial Direct Current Stimulation Treatment in Neuropsychiatry Trials. [2018]Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation investigated as a treatment for several neuropsychiatric disorders. Notwithstanding tDCS-induced adverse events (AEs) are considered to be low and transient, systematic review analyses on safety and tolerability of tDCS derive mostly from single-session studies.
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]Transcranial direct current stimulation (tDCS) has been proposed as novel treatment for major depressive disorder (MDD) based on clinical pilot studies as well as randomized controlled monocentric trials. The DepressionDC trial is a triple-blind (blinding of rater, operator and patient), randomized, placebo controlled multicenter trial investigating the efficacy and safety of prefrontal tDCS used as additive treatment in MDD patients who have not responded to selective serotonin reuptake inhibitors (SSRI). At 5 study sites, 152 patients with MDD receive a 6-weeks treatment with active tDCS (anode F3 and cathode F4, 2 mA intensity, 30 min/day) or sham tDCS add-on to a stable antidepressant medication with an SSRI. Follow-up visits are at 3 and 6 months after the last tDCS session. The primary outcome measure is the change of the Montgomery-Asberg Depression Rating Scale (MADRS) scores at week 6 post-randomisation compared to baseline. Secondary endpoints also cover other psychopathological domains, and a comprehensive safety assessment includes measures of cognition. Patients undergo optional investigations comprising genetic testing and functional magnetic resonance imaging (fMRI) of structural and functional connectivity. The study uses also an advanced tDCS technology including standard electrode positioning and recording of technical parameters (current, impedance, voltage) in every tDCS session. Aside reporting the study protocol here, we present a novel approach for monitoring technical parameters of tDCS which will allow quality control of stimulation and further analysis of the interaction between technical parameters and clinical outcome. The DepressionDC trial will hopefully answer the important clinical question whether prefrontal tDCS is a safe and effective antidepressant intervention in patients who have not sufficiently responded to SSRIs.
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]Major Depressive Disorder (MDD) is one of the most prevalent psychiatric disorders worldwide. About 20-30% of patients do not respond to the standard psychopharmacological and/or psychotherapeutic interventions. Mounting evidence from neuroimaging studies in MDD patients reveal altered activation patterns in lateral prefrontal brain areas. Successful cognitive behavioral therapy (CBT) is associated with a recovery of these neural alterations. Moreover, it has been demonstrated that transcranial direct current stimulation (tDCS) is capable of influencing prefrontal cortex activity and cognitive functions such as working memory and emotion regulation. Thus, a clinical trial investigating the effects of an antidepressant intervention combining CBT with tDCS seems promising. The present study investigates the antidepressant efficacy of a combined CBT-tDCS intervention as compared to CBT with sham-tDCS or CBT alone. A total of 192 patients (age range 20-65 years) with MDD (Hamilton Depression Rating Scale Score ≥ 15, 21-item version) will be recruited at four study sites across Germany (Berlin, Munich, Tuebingen, and Freiburg) and randomly assigned to one of the following three treatment arms: (1) CBT + active tDCS; (2) CBT + sham-tDCS; and (3) CBT alone. All participants will attend a 6-week psychotherapeutic intervention comprising 12 sessions of CBT each lasting 100 min in a closed group setting. tDCS will be applied simultaneously with CBT. Active tDCS includes stimulation with an intensity of 2 mA for 30 min with the anode placed over F3 and the cathode over F4 according to the EEG 10-20 system, if assigned. The primary outcome measure is the change in Montgomery-Åsberg Depression Rating Scale scores from baseline to 6, 18, and 30 weeks after the first session. Participants also undergo pre- and post-treatment neuropsychological testing and functional magnetic resonance imaging (fMRI) to assess changes in prefrontal functioning and connectivity. The study investigates whether CBT can be augmented by non-invasive brain stimulation techniques such as tDCS in the treatment of MDD. It is designed as a proof-of-principle trial for the combined tDCS-CBT treatment, but also allows the investigation of the neurobiological underpinnings of the interaction between both interventions in MDD. Trial registration ClinicalTrials.gov Identifier NCT02633449.
Safety of Transcranial Direct Current Stimulation of Frontal, Parietal, and Cerebellar Regions in Fasting Healthy Adults. [2020](1) Background: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation modality that has been investigated in a large number of studies in terms of it is effects on brain function, safety of use, and future implications. The principal aim of this study was to investigate the safety of 1.5-mA tDCS of three brain areas, that is, frontal, partial, and cerebellar cortices, in fasting healthy individuals during the month of Ramadan. (2) Methods: In a single-blinded, sham-controlled study, we assessed the safety of a 20-min tDCS current (1.5 mA, 35 cm²) over the right frontal, parietal, and cerebellar cortex areas after 8 h of fasting in healthy right-handed adult subjects using a standard safety questionnaire. (3) Results: A total of 49 subjects completed the tDCS sessions and safety questionnaire. None of the sessions were stopped due to pain or discomfort during stimulation. Moreover, no subject experienced serious adverse events such as seizures or loss of consciousness. (4) Conclusions: There was no significant difference in the frequency or type of side effects between active and sham stimulation sessions. The tDCS protocol applied in this study was found to be safe in fasting healthy adults.
Molecular basis and clinical perspectives of deep brain stimulation for major depressive disorder. [2023]It is possible to consider the stimulation of the cingulate gyrus in its portion below the corpus callosum (SCC, or subcallosal cingulate cortex) as an effective, promising, and safe alternative intervention for treatment-resistant depression. In studies with deep brain stimulation - DBS, when follow-on with functional magnetic resonance imaging and/or PET-CT (Positron emission tomography-computed tomography) is performed, it is observed an increase in the blood supply and glucose metabolism in this region, which is the anterior part of the limbic system. This same location has good experimental results also for the treatment of anorexia nervosa. The hypotheses suggest a greater activation of the reward system, a greater sense of well-being, and a consequent reduction in depressive symptoms, the objective of the treatment. Over the last 20 years, multicenter studies have shown symptomatic improvement in 50-60% of patients, and about a third even reach criteria for remission of the depressive disorder.
A Clinical Case Series of Acute and Maintenance Home Administered Transcranial Direct Current Stimulation in Treatment-Resistant Depression. [2023]Transcranial direct current stimulation (tDCS) is a noninvasive neurostimulation technique being translated clinically for the treatment of depression. There is limited research documenting the longer-term effectiveness and safety of tDCS treatment. This case series is the first report of remotely supervised, home-administered tDCS (HA-tDCS) for depression in a clinical setting.
TDCS at home for depressive disorders: an updated systematic review and lessons learned from a prematurely terminated randomized controlled pilot study. [2023]The application of transcranial direct current stimulation (tDCS) at home for the treatment of major depressive disorder (MDD) is the subject of current clinical trials. This is due to its positive safety profile, cost-effectiveness, and potential scalability for a wide outreach in clinical practice. Here, we provide a systematic review of the available studies and also a report on the results of a randomized controlled trial (RCT) on tDCS at home for the treatment of MDD. This trial had to be prematurely terminated due to safety concerns. The HomeDC trial is a double-blinded, placebo-controlled, parallel-group study. Patients with MDD (DSM-5) were randomized to active or sham tDCS. Patients conducted tDCS at home for 6 weeks with 5 sessions/week (30 min at 2 mA) anode over F3, cathode over F4. Sham tDCS resembled active tDCS, with ramp-in and ramp-out periods, but without intermittent stimulation. The study was prematurely terminated due to an accumulation of adverse events (AEs, skin lesions), so that only 11 patients were included. Feasibility was good. Safety monitoring was not sufficient enough to detect or prevent AEs within an appropriate timeframe. Regarding antidepressant effects, the reduction in depression scales over time was significant. However, active tDCS was not superior to sham tDCS in this regard. Both the conclusions from this review and the HomeDC trial show that there are several critical issues with the use of tDCS at home that need to be addressed. Nevertheless the array of transcranial electric simulation (TES) methods that this mode of application offers, including tDCS, is highly interesting and warrants further investigation in high quality RCTs.
Home-administered transcranial direct current stimulation is a feasible intervention for depression: an observational cohort study. [2023]Transcranial direct current stimulation (tDCS) is an emerging treatment for major depression. We recruited participants with moderate-to-severe major depressive episodes for an observational clinical trial using Soterix Medical's tDCS telehealth platform as a standard of care. The acute intervention consisted of 28 sessions (5 sessions/week, 6 weeks) of the left anodal dorsolateral prefrontal cortex (DLPFC) tDCS (2.0 mA × 30 min) followed by a tapering phase of weekly sessions for 4 weeks (weeks 7-10). The n = 16 completing participants had a significant reduction in depressive symptoms by week 2 of treatment [Montgomery-Åsberg Depression Rating Scale (MADRS), Baseline: 28.00 ± 4.35 vs. Week 2: 17.12 ± 5.32, p < 0.001] with continual improvement across each biweekly timepoint. Acute intervention responder and remission rates were 75 and 63% and 88 and 81% following the taper period (week 10).