CRS Array Brain-Machine Interface for Spinal Cord Injury

(CRS-BMI Trial)

Recruiting at 1 trial location

Overseen By Debbie Harrington

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Michael Boninger

Must not be taking: Sedatives, Anti-epileptics, Steroids, Immunosuppressants

Disqualifiers: Visual impairment, Serious disease, Active infection, 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

30 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this research study is to demonstrate the safety and efficacy of using two CRS Arrays (microelectrodes) for long-term recording of brain motor cortex activity and microstimulation of brain sensory cortex.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on medications that affect motor coordination or cognitive ability, you may not be eligible to participate.

What data supports the effectiveness of the treatment CRS Arrays, Utah Array, Michigan Probe, Microelectrode Arrays for spinal cord injury?

Research shows that microelectrode arrays can help map spinal cord activity with high precision and have been used to restore movement in paralyzed rats, suggesting potential benefits for spinal cord injury treatment. ^{1 2 3 4 5}

Is the Utah Array safe for use in humans?

The Utah Array has a strong track record of safety, but it can cause scar tissue formation around the electrodes, which may affect its performance. Studies in non-human primates and humans show that the arrays can last for years, although some electrode damage and neuron loss have been observed. ^{6 7 8 9 10}

How is the CRS Array Brain-Machine Interface treatment different from other treatments for spinal cord injury?

The CRS Array Brain-Machine Interface is unique because it uses microelectrode arrays to directly connect the brain and spinal cord, allowing real-time control of muscle movements by converting brain signals into electrical stimuli. This approach is different from traditional treatments as it aims to restore function by leveraging advanced bioelectronics and neural interfaces, rather than relying on physical therapy or medication. ^{2 3 11 12 13}

Research Team

Michael L Boninger, MD

Principal Investigator

University of Pittsburgh

Eligibility Criteria

This trial is for adults aged 22-70 with severe hand function loss due to specific injuries or conditions, able to follow study procedures and communicate in English. They must have a stable support system, live within 2 hours of the University of Pittsburgh, and not have worsening neurological status. Excluded are those with visual impairments, active infections, excessive alcohol consumption, certain diseases that affect participation ability, metal implants incompatible with MRI scans, uncontrolled diabetes or seizures.

Inclusion Criteria

You are expected to live for more than 18 months.

I understand the study's goals and can follow simple instructions.

I have reliable support for daily skin and pedestal site care.

Exclusion Criteria

You have trouble seeing things on a computer screen even with glasses.

You have metal implants that would prevent you from having an fMRI scan.

You have any kind of implantable device like a pacemaker, cochlear implant, or defibrillator.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Implantation and Initial Training

Participants undergo implantation of microelectrodes and initial training to use the brain-machine interface

4-8 weeks

Long-term Evaluation

Participants are evaluated for safety and efficacy of the brain-machine interface over a 12-month period

12 months

Follow-up

Participants are monitored for safety and effectiveness after the main evaluation period

4 weeks

Treatment Details

Interventions

• CRS Arrays

Trial Overview The trial tests the safety and effectiveness of CRS Arrays (microelectrodes) implanted in the brain. These devices record motor cortex activity and stimulate sensory cortex to potentially restore movement control or sensation in individuals with severe upper limb disabilities.

Participant Groups

Group I: Brain-Machine Interface Users Experimental Treatment 1 Intervention

All participants enrolled in the study who meet eligibility criteria will be individuals implanted with microelectrodes in their brain to record neural activity. There is no control group.

CRS Arrays is already approved in United States for the following indications:

Approved in United States as Utah Array for:

• Motor brain-machine interfaces for paralyzed patients
• Clinical investigations of intracortical brain-machine interface technology

Who Is Running the Clinical Trial?

Michael Boninger

Lead Sponsor

Trials

3

Recruited

230+

University of Chicago

Collaborator

Trials

1,086

Recruited

844,000+

Northwestern University

Collaborator

Trials

1,674

Recruited

989,000+

Carnegie Mellon University

Collaborator

Trials

80

Recruited

540,000+

Sinai Health System

Collaborator

Trials

26

Recruited

11,900+

Findings from Research

The study developed a parylene-based microelectrode array implant for the epidural spinal cord, which was tested on rats with hindlimb paralysis due to spinal cord injury, showing recovery of stepping functionality over an eight-week period.

This advanced implant offers greater precision in stimulation compared to traditional wire-based devices, potentially enhancing our understanding of spinal cord recovery mechanisms and improving rehabilitation strategies for spinal cord injury patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A PARYLENE-BASED MICROELECTRODE ARRAY IMPLANT FOR SPINAL CORD STIMULATION IN RATS. Nandra, MS., Lavrov, IA., Edgerton, VR., et al.[2021]

The use of a microelectrode array during spine surgery allows for high-resolution mapping of spinal cord activity, providing detailed spatiotemporal information that traditional intraoperative neuromonitoring (IONM) methods cannot achieve.

This advanced technique enables the recording of neural responses at lower stimulation currents and can detect postoperative evoked potentials, potentially improving the safety and effectiveness of surgical procedures by offering better electrophysiological markers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Constructing 2D maps of human spinal cord activity and isolating the functional midline with high-density microelectrode arrays. Russman, SM., Cleary, DR., Tchoe, Y., et al.[2022]

Microelectrode arrays, traditionally used for studying the brain, can also effectively record and stimulate the spinal cord, particularly in the corticospinal tract of animal models.

This innovative application of microelectrodes may lead to new therapeutic approaches for treating severe spinal cord injuries by enhancing our understanding of spinal cord function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Localized stimulation and recording in the spinal cord with microelectrode arrays. Arle, JE., Shils, JL., Malik, WQ.[2020]

Neuroprosthetics are advancing with new microelectrode arrays that can selectively stimulate neurons and record their activity, potentially restoring lost neural functions.

However, the long-term effectiveness and safety of these implanted microelectrodes in humans are still uncertain, particularly regarding the tissue damage they may cause, which needs to be managed for successful clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute human brain responses to intracortical microelectrode arrays: challenges and future prospects. Fernández, E., Greger, B., House, PA., et al.[2021]

The new intermediary mounting plate design for skull-mounted connectors significantly reduces the failure rate of attachments in brain-machine interfaces, as tested in three non-human primates.

Key features of the design, such as wide legs for force distribution and a two-stage fixation process, enhance stability and promote osseointegration, leading to improved outcomes for subjects in intracortical recording experiments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baseplate for two-stage cranial mounting of BMI connectors. McMorland, AJ., Velliste, M.[2013]

The study evaluated the chronic performance of 16-channel Utah electrode arrays in rat motor cortex over 6 months, revealing a significant decline in recording capability, with single-unit active electrode yield dropping from 52.8% to 13.4%.

The findings indicated that the main issues affecting performance were abiotic failures, such as mechanical wire breakage and degradation of the electrode materials, which could impact the reliability of these devices for long-term studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic recording and electrochemical performance of Utah microelectrode arrays implanted in rat motor cortex. Black, BJ., Kanneganti, A., Joshi-Imre, A., et al.[2019]

In a study involving a rhesus macaque, it was found that implanted Utah arrays led to a 63% reduction in the number of neurons surrounding the electrodes compared to control areas, indicating significant neuron loss due to the tissue response.

Despite some material damage observed, such as tip breakage and cracks, the arrays remained largely intact, suggesting that improvements in electrode design, like using smaller or softer probes, could enhance tissue response and improve neural recording capabilities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utah array characterization and histological analysis of a multi-year implant in non-human primate motor and sensory cortices. Patel, PR., Welle, EJ., Letner, JG., et al.[2023]

In a comprehensive analysis of over 6000 datasets from 17 rhesus macaques and 2 human subjects, Utah electrode arrays (UEAs) demonstrated an average lifespan of 622 days for reliable recordings, with some lasting over 1000 days and even up to 9 years.

The study found that human implants generally lasted longer than those in non-human primates, and that the type of metallization on the electrode tip (iridium oxide vs. platinum) significantly influenced the quality and longevity of the recordings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Longevity and reliability of chronic unit recordings using the Utah, intracortical multi-electrode arrays. Sponheim, C., Papadourakis, V., Collinger, JL., et al.[2022]

This study highlights significant variability in the duration of chronic studies using microelectrode arrays (MEAs) across different animal species, particularly in rodents, which are commonly used for such research.

The active electrode yield (AEY) in rodent models showed a linear decay over time with commercially-available devices, emphasizing the need for consistent benchmarks to evaluate the performance of new MEA technologies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracortical Microelectrode Array Unit Yield under Chronic Conditions: A Comparative Evaluation. Usoro, JO., Sturgill, BS., Musselman, KC., et al.[2021]

Recent advancements in penetrating microelectrode arrays, such as Utah electrode arrays, have shown promise in recording motor commands from the central nervous system, which could lead to improved therapies for motor disorders.

These microelectrode arrays can also evoke sensory perceptions in the peripheral nervous system, suggesting their potential to enhance the quality of life for patients with neurological disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical applications of penetrating neural interfaces and Utah Electrode Array technologies. Normann, RA., Fernandez, E.[2018]

The development of a miniaturized brain-machine-spinal cord interface (BMSI) shows promise for restoring mobility in individuals with spinal cord injuries by converting neural signals into electrical stimuli for the spinal cord.

In a proof-of-concept study with anesthetized rats, the BMSI successfully activated distinct muscle patterns through intraspinal microstimulation, demonstrating the potential for real-time control of movement based on brain activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cortical control of intraspinal microstimulation: Toward a new approach for restoration of function after spinal cord injury. Shahdoost, S., Frost, S., Dunham, C., et al.[2020]

Carbon fiber microelectrode bundles were successfully developed and implanted in the spinal cord of experimental animals, allowing for effective in vivo recording of neural signals, including single spikes.

The removal of a small portion of the coating at the tips of the electrodes improved the signal-to-noise ratio, and the design showed minimal tissue encapsulation, indicating good biocompatibility and potential for long-term use in neural recordings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carbon Fiber Electrodes for in Vivo Spinal Cord Recordings. Cetinkaya, E., Gok, S., Sahin, M.[2020]

Brain-machine interfaces (BMIs) have the potential to restore motor and sensory functions in amputees and patients with spinal cord injuries by allowing voluntary control over prosthetic limbs or paralyzed muscles.

Recent advancements in decoding motor intentions from brain activity and providing sensory feedback through electrical stimulation show promise for these invasive interfaces, but significant challenges still need to be addressed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Restoring sensorimotor function through intracortical interfaces: progress and looming challenges. Bensmaia, SJ., Miller, LE.[2022]

References

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

A PARYLENE-BASED MICROELECTRODE ARRAY IMPLANT FOR SPINAL CORD STIMULATION IN RATS. [2021]

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

Constructing 2D maps of human spinal cord activity and isolating the functional midline with high-density microelectrode arrays. [2022]

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

Localized stimulation and recording in the spinal cord with microelectrode arrays. [2020]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Acute human brain responses to intracortical microelectrode arrays: challenges and future prospects. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Baseplate for two-stage cranial mounting of BMI connectors. [2013]

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

Chronic recording and electrochemical performance of Utah microelectrode arrays implanted in rat motor cortex. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Utah array characterization and histological analysis of a multi-year implant in non-human primate motor and sensory cortices. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Longevity and reliability of chronic unit recordings using the Utah, intracortical multi-electrode arrays. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Intracortical Microelectrode Array Unit Yield under Chronic Conditions: A Comparative Evaluation. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Clinical applications of penetrating neural interfaces and Utah Electrode Array technologies. [2018]

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

Cortical control of intraspinal microstimulation: Toward a new approach for restoration of function after spinal cord injury. [2020]

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

Carbon Fiber Electrodes for in Vivo Spinal Cord Recordings. [2020]

13. England pubmed.ncbi.nlm.nih.gov

Restoring sensorimotor function through intracortical interfaces: progress and looming challenges. [2022]