Pascal Device for Long COVID Syndrome

Recruiting in Palo Alto (17 mi)

Overseen by David Putrino

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Icahn School of Medicine at Mount Sinai

Must not be taking: Immunomodulatory, Psychoactive

Disqualifiers: Bipolar, Psychotic, Substance use, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

The purpose of this study is to assess the feasibility of an at-home MMT treatment in patients with cognitive dysfunction related to PASC, and to collect data on safety and efficacy to inform the design of larger clinical studies. A prospective randomized controlled study of 30 participants with PASC and moderate to severe cognitive dysfunction. Total study duration will be 8 weeks, including 4 weeks of treatment and 4 weeks of untreated follow up.

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 certain ongoing immunomodulatory medications like NSAIDs or corticosteroids.

What data supports the effectiveness of the Pascal Device for Long COVID Syndrome treatment?

The research on brain-responsive neurostimulation devices, like the RNS System used for epilepsy, suggests that similar neurotechnological approaches could be effective for treating episodic neurological disorders. This indicates potential for the Pascal Device, which may use similar technology, to help manage symptoms of Long COVID Syndrome. ^{1 2 3 4 5}

Is the Pascal Device for Long COVID Syndrome safe for humans?

The Pascal Device, also known as the Humanity Neurotech Device, has been evaluated in a clinical trial for drug-resistant epilepsy, where no adverse effects were observed, suggesting it is generally safe for human use. ^{6 7 8 9 10}

How is the Pascal Device treatment for Long COVID Syndrome different from other treatments?

The Pascal Device treatment is unique because it uses a wireless brain-machine interface (BMI) to record and stimulate brain activity, potentially enhancing sensory-motor functions. This approach is novel compared to traditional treatments, as it involves a non-invasive, wireless system that can be recharged externally, offering a new way to manage symptoms by directly interacting with brain functions. ^{11 12 13 14 15}

Research Team

David Putrino

Principal Investigator

Icahn School of Medicine at Mount Sinai

Eligibility Criteria

This trial is for adults with cognitive issues after recovering from COVID, often called 'Long COVID'. Participants should have moderate to severe memory or thinking problems since their illness. The study excludes individuals who are currently using other cognitive therapies or devices, those with implanted electronic medical devices, and pregnant women.

Inclusion Criteria

Individuals of childbearing age agreeing to use a highly effective form of birth control

I speak English.

Objective cognitive impairment on neuropsychological measures (as defined by a z-score ≥1 standard deviation below the normative mean) in executive functioning

Exclusion Criteria

Enrollment in another interventional clinical trial in the last 90 days or during the study period

History of cognitive dysfunction present prior to SARS CoV-2 infection

Febrile (> 99 F) at the time of the enrollment visit

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive at-home MMT treatment for cognitive dysfunction related to PASC

4 weeks

At-home treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Humanity Neurotech Device (Behavioural Intervention)

Trial Overview The trial is testing the Pascal device, which is a new technology aimed at improving brain function in Long COVID patients. Half of the participants will receive this active device while the other half will get a sham (inactive) device as a comparison over four weeks of treatment.

Participant Groups

Group I: Active device Experimental Treatment 1 Intervention

The active device will generate a low amplitude magnetic field. 20 participants will be randomized to this arm.

Group II: Sham device Placebo Group 1 Intervention

The sham device will not generate a low amplitude magnetic field. 10 participants will be randomized to this arm.

Who Is Running the Clinical Trial?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

Dr. Brendan Carr

Icahn School of Medicine at Mount Sinai

Chief Executive Officer since 2024

MD, MA, MS

Dr. Vicki LoPachin

Icahn School of Medicine at Mount Sinai

Chief Medical Officer

MD, FACP, MBA

Humanity Neurotech Inc.

Collaborator

Trials

1

Recruited

30+

Findings from Research

Implantable brain-interfacing devices (IBIDs) are being developed for a variety of conditions, including movement disorders and psychiatric issues like depression and OCD, marking a significant expansion in their application since the first approval of deep brain stimulation in 1997.

As these devices target conditions related to personal identity and agency, understanding patients' perspectives on identity is crucial for informed consent and public policy discussions regarding their use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation, personal identity and policy. Mathews, DJ.[2011]

A group of neuroscientists is developing an implantable neural emulator aimed at replacing the damaged cerebellar functions in children suffering from cerebellar disease.

This innovative approach could potentially offer a new therapeutic option for restoring motor and cognitive functions affected by cerebellar damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Defending against cerebellar disease. Shadmehr, R.[2023]

The NeuroPace® RNS® System is a safe and effective neuromodulation device for patients with epilepsy who do not respond to traditional antiseizure medications, providing a nondestructive alternative to surgical resection.

Clinical trials have shown that the RNS System can detect and respond to epileptiform activity by delivering targeted electrical stimulation, which may lead to improved seizure control and could be adapted for other neurological disorders using advanced machine learning techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The RNS System: brain-responsive neurostimulation for the treatment of epilepsy. Jarosiewicz, B., Morrell, M.[2021]

Invasive Brain-Machine Interface (BMI) technology has shown promise in allowing individuals with severe movement and communication disorders to directly control assistive devices, as demonstrated in recent pilot clinical studies.

These studies have sparked interest among healthcare providers and patients, highlighting the potential of BMI technology to improve the quality of life for people with disabilities, while also addressing the challenges and future directions for its clinical application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cortical neuroprosthetics from a clinical perspective. Tsu, AP., Burish, MJ., GodLove, J., et al.[2021]

A mobile application and remote monitoring support center were developed to enhance the management of chronic pain patients, ensuring adherence to follow-up protocols and improving patient care.

Initial evaluations from users indicated that the application was useful, leading to minor adjustments for better usability, which highlights the importance of user feedback in healthcare technology development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of an integrated solution for patients with neurostimulator for chronic pain in times of COVID-19: A mobile application with a support center. Cordero Tous, N., Santos Martín, L., Sánchez Corral, C., et al.[2022]

A new cell therapy using GABAergic interneurons derived from human embryonic stem cells showed promising results in a mouse model of drug-resistant mesial temporal lobe epilepsy (MTLE), significantly reducing seizures and improving survival rates.

The therapy demonstrated long-term integration and functional effects in the brain without any observed adverse effects, supporting its potential for use in clinical trials for patients with drug-refractory MTLE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human pallial MGE-type GABAergic interneuron cell therapy for chronic focal epilepsy. Bershteyn, M., Bröer, S., Parekh, M., et al.[2023]

Human induced pluripotent stem cell (iPSC)-derived long-term neuroepithelial stem (lt-NES) cells can produce myelinating oligodendrocytes and neurons that integrate into stroke-injured brain networks, showing promise for repairing brain damage.

These oligodendrocytes not only survive after being grafted into adult human cortical cultures but also successfully form myelin around human axons, indicating their potential for clinical recovery in brain injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oligodendrocytes in human induced pluripotent stem cell-derived cortical grafts remyelinate adult rat and human cortical neurons. Martinez-Curiel, R., Jansson, L., Tsupykov, O., et al.[2023]

Proinflammatory cytokines IL-1β and TNF-α significantly increased neurite lengths and levels of neurotrophins (BDNF, NT3, GDNF) in human annulus cell-F11 nerve cell cocultures, suggesting that inflammation may enhance nerve growth in degenerating discs.

The study indicates that the inflammatory environment in degenerated discs could promote nerve migration, which may have clinical implications for understanding pain mechanisms associated with nerve ingrowth in the outer annulus of intervertebral discs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proinflammatory Cytokines IL-1β and TNF-α Influence Human Annulus Cell Signaling Cues for Neurite Growth: In Vitro Coculture Studies. Gruber, HE., Jones, B., Marrero, E., et al.[2021]

In a study using a rat model of perinatal hypoxic ischemic encephalopathy (HIE), intravenous transplantation of human Muse cells led to significant improvements in motor and cognitive functions over 5 months, indicating their potential as a therapeutic intervention.

Muse cells were found to migrate primarily to the injured brain and regulate glutamate metabolism while reducing microglial activation, suggesting a mechanism of action that may protect against neurological damage following HIE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenously delivered multilineage-differentiating stress enduring cells dampen excessive glutamate metabolism and microglial activation in experimental perinatal hypoxic ischemic encephalopathy. Suzuki, T., Sato, Y., Kushida, Y., et al.[2021]

In a study involving patients with neurological disorders who received fetal pig neuronal cell transplants, there was no evidence of porcine endogenous retrovirus (PERV) transmission, as tested in blood samples from 24 recipients.

In vitro experiments also confirmed that PERV did not transfer from fetal pig neuronal cells to human cells, indicating a low risk for PERV infection in these transplantation therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

No evidence for infection of human cells with porcine endogenous retrovirus (PERV) after exposure to porcine fetal neuronal cells. Dinsmore, JH., Manhart, C., Raineri, R., et al.[2019]

Research at the intersection of neuroscience and electronics is paving the way for innovative implants that can target cells for therapy, potentially transforming treatments for neurodegenerative and neuropsychiatric disorders.

Emerging tissue-like electronics are expected to lead to minimally invasive devices that can create stable, long-term connections with neural cells, offering new options for managing chronic neurological conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Precision electronic medicine in the brain. Patel, SR., Lieber, CM.[2023]

A new 16-channel epicortical grid was successfully implanted in a non-human primate, allowing for wireless recording and stimulation of the motor and sensory cortices, which could help overcome current limitations in brain-machine interfaces (BMIs).

The grid demonstrated effective stimulation of motor functions without interfering with natural sensory processing, indicating its potential for safe and effective use in both experimental and clinical BMI applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel wireless recording and stimulating multichannel epicortical grid for supplementing or enhancing the sensory-motor functions in monkey (Macaca fascicularis). Zippo, AG., Romanelli, P., Torres Martinez, NR., et al.[2020]

The study successfully created 3D neural aggregates from a single human tissue sample, including neurons, astrocytes, and oligodendroglial cells, which can form functional neuronal circuits.

Using microelectrode array (MEA) technology, the researchers demonstrated that these neurons could establish a highly synchronous network within just 3 weeks in vitro, enabling personalized models for studying neurological and neuropsychiatric diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Robust Generation of Person-Specific, Synchronously Active Neuronal Networks Using Purely Isogenic Human iPSC-3D Neural Aggregate Cultures. Izsak, J., Seth, H., Andersson, M., et al.[2020]

The ECOGIW-16E device is a fully implantable, wireless system designed for electrocorticographic (ECoG) recording and cortical stimulation in non-human primates, enhancing safety by eliminating external cables.

This device successfully recorded brain activity and delivered targeted brain stimulation, demonstrating its potential for chronic monitoring and improving procedures for epilepsy treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A fully integrated wireless system for intracranial direct cortical stimulation, real-time electrocorticography data transmission, and smart cage for wireless battery recharge. Piangerelli, M., Ciavarro, M., Paris, A., et al.[2021]

Over one third of the 60 million people with epilepsy experience uncontrolled seizures, and current surgical options only lead to seizure freedom in about 35% of cases, highlighting the urgent need for new treatments.

The research team has developed innovative implantable brain devices using flexible silicon nanoribbons that can record from very small brain regions with high precision, potentially enabling better mapping of epileptic networks and improving treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of high resolution, multiplexed electrode arrays: Opportunities and challenges. Viventi, J., Blanco, JA.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Deep brain stimulation, personal identity and policy. [2011]

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

Defending against cerebellar disease. [2023]

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

The RNS System: brain-responsive neurostimulation for the treatment of epilepsy. [2021]

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

Cortical neuroprosthetics from a clinical perspective. [2021]

5. Spain pubmed.ncbi.nlm.nih.gov

Development of an integrated solution for patients with neurostimulator for chronic pain in times of COVID-19: A mobile application with a support center. [2022]

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

Human pallial MGE-type GABAergic interneuron cell therapy for chronic focal epilepsy. [2023]

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

Oligodendrocytes in human induced pluripotent stem cell-derived cortical grafts remyelinate adult rat and human cortical neurons. [2023]

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

Proinflammatory Cytokines IL-1β and TNF-α Influence Human Annulus Cell Signaling Cues for Neurite Growth: In Vitro Coculture Studies. [2021]

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

Intravenously delivered multilineage-differentiating stress enduring cells dampen excessive glutamate metabolism and microglial activation in experimental perinatal hypoxic ischemic encephalopathy. [2021]

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

No evidence for infection of human cells with porcine endogenous retrovirus (PERV) after exposure to porcine fetal neuronal cells. [2019]

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

Precision electronic medicine in the brain. [2023]

12. Switzerland pubmed.ncbi.nlm.nih.gov

A novel wireless recording and stimulating multichannel epicortical grid for supplementing or enhancing the sensory-motor functions in monkey (Macaca fascicularis). [2020]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Robust Generation of Person-Specific, Synchronously Active Neuronal Networks Using Purely Isogenic Human iPSC-3D Neural Aggregate Cultures. [2020]

14. Switzerland pubmed.ncbi.nlm.nih.gov

A fully integrated wireless system for intracranial direct cortical stimulation, real-time electrocorticography data transmission, and smart cage for wireless battery recharge. [2021]

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

Development of high resolution, multiplexed electrode arrays: Opportunities and challenges. [2021]