Neurostimulation for Healthy Subjects

(CAMSAN Trial)

Overseen By Zoe Steine-Hanson, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: OpenBCI

Must not be taking: ADHD medications, Mind-altering drugs

Disqualifiers: PTSD, ADHD, Substance abuse, others

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

Compensation: Varies

Number of Visits: Unknown

50 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to extend this period of optimal cognitive performance by applying neurostimulation to buffer health volunteers against the effects of increased levels of stress, distraction, and cybersickness. The main questions it aims to answer are: * Can we use OpenBCI's head-mounted Galea biosensor + eXtended Reality (XR) platform to measure participants' cognitive state in relation to stress, attention and cybersickness? * How does applying external neurostimulation via Spark Biomedical's Sparrow Link transcutaneous auricular neurostimulation (tAN) system enhance cognitive performance with a closed-loop interface that automatically applies neurostimulation as a function of physiologically determined stress, attention, and cybersickness metrics? Researchers will compare the active neurostimulation group to the sham neurostimulation group to see if cognitive performance is improved with stimulation. Participants will complete 4 virtual reality tasks in the lab: * 2 tasks related to attention - Flanker and Gradual-onset Continual Performance Task (GradCPT) * The Multi-Attribute Task Battery (MATB) * A cybersickness task * And a baseline session before each task * Neurostimulation intervention will occur in response to cognitive states

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently taking medications for ADHD or have a recent history of substance abuse or drug dependence.

What data supports the effectiveness of the treatment Active Neurostimulation for healthy subjects?

The research suggests that individuals who do not respond to sham stimulation are more likely to respond to active neurostimulation, indicating that the treatment may be effective for certain individuals. Additionally, the use of neurostimulation in other conditions, like neuropathic pain, has shown positive effects, suggesting potential benefits in healthy subjects as well. ^{1 2 3 4 5}

Is neurostimulation safe for healthy individuals?

Neurostimulation, including various forms like transcranial electrical stimulation (tES), is generally considered safe for healthy individuals. Over 18,000 sessions have shown no serious adverse events, with only mild effects like headaches or skin sensations reported. Safety is well-established for low-intensity sessions, and adverse events are similar in both healthy and clinical populations. ^{1 6 7 8 9}

How does the neurostimulation treatment differ from other treatments for this condition?

The neurostimulation treatment is unique because it uses non-invasive brain stimulation techniques like transcranial direct current stimulation (tDCS) to modulate brain activity, which is different from traditional drug-based treatments. This approach is novel as it involves applying electrical currents to the scalp to influence brain function without the use of medication. ^{1 2 5 10 11}

Research Team

Navid Khodaparast, PhD

Principal Investigator

Spark Biomedical

Conor Russomanno, Masters

Principal Investigator

OpenBCI

Alejandro Covalin, PhD

Principal Investigator

Spark Biomedical

Musa Mahmood, PhD

Principal Investigator

OpenBCI

Zoe Steine-Hanson, PhD

Principal Investigator

OpenBCI

Eligibility Criteria

This trial is for healthy volunteers who want to help test if a device that stimulates the ear can improve attention and reduce stress or cybersickness during virtual reality tasks. People with cognitive impairments can also join.

Inclusion Criteria

Normal color vision and near visual acuity of 20/30 without correction

Participant is right-hand dominant

I can understand the study instructions and explanations.

Exclusion Criteria

Current or recent history of substance abuse or drug dependence including nicotine and alcohol, or use of mind-altering drugs in the past 30 days

I have ear issues that may affect treatment.

I am not pregnant or breastfeeding.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I: Preliminary Cognitive State Assessment

Establish a cognitive task performance baseline and quantify cognitive state metrics based on biomarkers. Participants perform tasks such as Flanker Task, GradCPT, MATB, and a cybersickness stimulation task.

4 weeks

Multiple visits (in-person)

Phase II: Open-loop Intervention

Evaluation of manual tAN to affect cognitive state in an open-loop paradigm. Participants perform the same tasks while wearing the Sparrow Link tAN device.

4 weeks

Multiple visits (in-person)

Phase III: Closed-loop Intervention

Examine a closed-loop cognitive augmentation system using active tAN, triggered based on conditions determined by the investigating team. Participants perform the same tasks as in previous phases.

4 weeks

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the intervention phases.

4 weeks

Treatment Details

Interventions

• Active Neurostimulation
• Sham Stimulation

Trial Overview The study tests whether a head-mounted sensor combined with an ear-stimulating device improves cognitive performance by responding to signs of stress, distraction, and cybersickness during VR tasks.

Participant Groups

Group I: Active tAN Experimental Treatment 1 Intervention

This group receives active neurostimulation at different intervals, amplitudes, and frequencies via the Sparrow Link device.

Group II: Sham Stimulation Placebo Group 1 Intervention

The sham group will receive a device but no stimulation will be delivered.

Who Is Running the Clinical Trial?

OpenBCI

Lead Sponsor

Trials

1

Recruited

50+

Spark Biomedical, Inc.

Industry Sponsor

Trials

14

Recruited

560+

Findings from Research

A systematic review and meta-analysis of 30 randomized controlled trials found that sham transcranial electrical stimulation (tES) does not significantly affect corticospinal excitability (CSE) in healthy individuals.

The study highlights the importance of ensuring that sham stimulation closely mimics active stimulation to maintain the integrity of blinding in clinical trials, as the effects of sham tES were statistically non-significant compared to baseline.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sham transcranial electrical stimulation and its effects on corticospinal excitability: a systematic review and meta-analysis. Dissanayaka, TD., Zoghi, M., Farrell, M., et al.[2018]

In a study of 30 healthy young adults, it was found that individuals who did not show changes in corticospinal excitability during sham stimulation were more likely to respond positively to active transcranial non-invasive brain stimulation (tNIBS) techniques, such as tRNS and tACS.

This suggests that the response to sham stimulation can serve as a predictor for individual responses to active stimulation, highlighting the importance of considering baseline brain reactivity when designing future tNIBS studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of tRNS and 140 Hz tACS on motor cortex excitability seemingly dependent on sensitivity to sham stimulation. Kortuem, V., Kadish, NE., Siniatchkin, M., et al.[2022]

In a study involving 33 patients undergoing rTMS treatment, the sham condition used was effective as most participants could not distinguish between real and sham stimulation, indicating its suitability for clinical trials.

Both groups, those receiving real stimulation and those receiving sham, showed a high willingness to recommend rTMS to others, suggesting that the treatment is perceived positively regardless of the actual stimulation received.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sham or real--post hoc estimation of stimulation condition in a randomized transcranial magnetic stimulation trial. Herwig, U., Cardenas-Morales, L., Connemann, BJ., et al.[2015]

In a study evaluating patients with neuropathic pain, implantation of a chronic epidural spinal cord stimulation system led to significant pain relief and improvements in brain function and metabolism related to pain perception and emotional responses.

The assessment was conducted using EEG and PET imaging with 18F-fluorodeoxyglucose, showing that the nerve stimulator not only alleviated pain but also partially normalized brain activity associated with pain and emotional processing after 3 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional and metabolic changes in the brain in neuropathic pain syndrome against the background of chronic epidural electrostimulation of the spinal cord. Sufianov, AA., Shapkin, AG., Sufianova, GZ., et al.[2014]

Transcranial direct current stimulation (tDCS) is a non-invasive technique used to modulate brain activity, but the effectiveness of active tDCS compared to sham tDCS has shown inconsistent results across studies.

The variability in sham tDCS protocols may lead to different biological effects, which could confound results and affect the reproducibility of tDCS research, highlighting the need for standardized sham protocols in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sham tDCS: A hidden source of variability? Reflections for further blinded, controlled trials. Fonteneau, C., Mondino, M., Arns, M., et al.[2019]

Low intensity transcranial electrical stimulation (TES) is considered safe, with no serious adverse events reported in over 18,000 sessions across various populations, including healthy individuals and patients with neurological or psychiatric conditions.

While moderate adverse events like skin burns from tDCS are rare, mild adverse events such as headaches and fatigue are more common, and the safety profile is consistent across different age groups and vulnerable populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines. Antal, A., Alekseichuk, I., Bikson, M., et al.[2023]

The Neurostimulation Appropriateness Consensus Committee (NACC) aims to enhance the safety of neurostimulation procedures by providing updated recommendations based on expert consensus and best evidence.

The International Neuromodulation Society (INS) has established guidelines that, when followed, are expected to minimize the risk of neurological injuries and complications associated with the surgical implantation of neurostimulation devices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Neurostimulation Appropriateness Consensus Committee (NACC) Safety Guidelines for the Reduction of Severe Neurological Injury. Deer, TR., Lamer, TJ., Pope, JE., et al.[2022]

Transcranial electrical stimulation (tES), including tDCS and MHF-tPCS, was found to be well tolerated in healthy subjects over a six-week period, with common side effects being mild skin sensations like tingling and itching, which were less frequent than in the sham-tDCS group.

The MHF-tPCS group showed significantly higher compliance in completing sessions compared to the sham-tDCS group, indicating that this waveform may be more acceptable for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability of Repeated Application of Transcranial Electrical Stimulation with Limited Outputs to Healthy Subjects. Paneri, B., Adair, D., Thomas, C., et al.[2018]

In a study involving 1,019 participants across 4 sites, adverse events (AEs) following multiple sessions of transcranial electrical stimulation (tES) were found to be influenced more by factors like testing site and session number rather than the stimulation itself, suggesting a good safety profile for repeated use.

The effectiveness of blinding procedures was found to be less reliable for tDCS and tACS compared to tRNS, indicating a need for improved blinding methods, especially when using higher stimulation intensities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blinding efficacy and adverse events following repeated transcranial alternating current, direct current, and random noise stimulation. Sheffield, JG., Ramerpresad, S., Brem, AK., et al.[2022]

The study found that the standard method of sham stimulation in transcranial electrical stimulation (tDCS) research, which involves slowly ramping down current intensity, does not completely eliminate the sensation of stimulation, making it difficult to effectively blind participants.

Experienced subjects were better at distinguishing between real and sham stimulation, indicating that the current blinding method may not be sufficient, as both sham and real conditions produced persistent sensations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The fade-in--short stimulation--fade out approach to sham tDCS--reliable at 1 mA for naïve and experienced subjects, but not investigators. Ambrus, GG., Al-Moyed, H., Chaieb, L., et al.[2022]

A new sham rTMS method was developed that effectively mimics the look, sound, and feel of active rTMS without producing a significant magnetic field, making it suitable for double-blind, placebo-controlled studies.

In tests with naïve subjects, they could not distinguish between active and sham stimulation, indicating the sham method's validity; however, experienced subjects could tell the difference, highlighting the need for careful participant selection in studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sham Transcranial Magnetic Stimulation Using Electrical Stimulation of the Scalp. Mennemeier, M., Triggs, W., Chelette, K., et al.[2023]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Sham transcranial electrical stimulation and its effects on corticospinal excitability: a systematic review and meta-analysis. [2018]

2. Germany pubmed.ncbi.nlm.nih.gov

Efficacy of tRNS and 140 Hz tACS on motor cortex excitability seemingly dependent on sensitivity to sham stimulation. [2022]

3. Ireland pubmed.ncbi.nlm.nih.gov

Sham or real--post hoc estimation of stimulation condition in a randomized transcranial magnetic stimulation trial. [2015]

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

Functional and metabolic changes in the brain in neuropathic pain syndrome against the background of chronic epidural electrostimulation of the spinal cord. [2014]

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

Sham tDCS: A hidden source of variability? Reflections for further blinded, controlled trials. [2019]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines. [2023]

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

The Neurostimulation Appropriateness Consensus Committee (NACC) Safety Guidelines for the Reduction of Severe Neurological Injury. [2022]

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

Tolerability of Repeated Application of Transcranial Electrical Stimulation with Limited Outputs to Healthy Subjects. [2018]

9. Italy pubmed.ncbi.nlm.nih.gov

Blinding efficacy and adverse events following repeated transcranial alternating current, direct current, and random noise stimulation. [2022]

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

The fade-in--short stimulation--fade out approach to sham tDCS--reliable at 1 mA for naïve and experienced subjects, but not investigators. [2022]

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

Sham Transcranial Magnetic Stimulation Using Electrical Stimulation of the Scalp. [2023]