Clinical Trial Details
— Status: Enrolling by invitation
Administrative data
| NCT number |
NCT05919160 |
| Other study ID # |
STUDY00002777 |
| Secondary ID |
|
| Status |
Enrolling by invitation |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
June 2024 |
| Est. completion date |
October 2025 |
Study information
| Verified date |
May 2024 |
| Source |
Cedars-Sinai Medical Center |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The purpose of this study is to test the ability of a newly-designed electrode to measure the
activity of individual nerve cells (neurons), and collections of nerve cells (local field
potentials) in the brain. The study's main goals are to see how well this electrode works
compared to standard electrodes and to validate its safety.
Description:
Recording of human brain activity at many scales is an important tool in clinical medicine.
The ability to record extracellular action potentials, otherwise known as a "single unit
activity" (SUA) has provided fundamental insight into the details of neuronal function in
humans as well as a variety of nonhuman animals. In humans the techniques for recording
extracellular action potentials are relatively limited. Rigid, sharp tipped probes
manufactured by several companies are FDA approved and routinely used as part of standard of
care during a variety of surgical procedures such as deep brain stimulation (DBS) device
implantation to identify areas of neuronal activity and optimize placement of clinical
electrodes. The same technique has been used to better understand brain function and its
impairment by disease in humans. In addition, a variety of semi- chronically implanted
microwire techniques are available. These electrodes are more commonly used in patients with
seizure disorders and have allowed insight into network behavior such as in the medial
temporal lobe and medial frontal lobe.
However there remains a tremendous gap between the recording capabilities of modern
electrodes used in animal research, and what is currently clinically available for human
testing. A typical rigid shaft single electrode currently used in clinical care will record
anywhere from 1-3 distinctly isolated neurons at a time. In contrast, in state-of-the art
animal research, higher density probes such as the Neuropixel electrode [4-6] now routinely
allow recording of hundreds or even thousands of neurons in a single brain region. This
markedly increased recording capability translates directly into a better understanding of
how brain neurons and networks interact to create complex behaviors and disease. Most of the
commonly used high-density electrodes are based on a rigid silicon shaft onto which multiple
recording contacts (typically made of platinum, Iridium, gold or conductive polymers) are
embedded. There are several significant limitations of silicon-based probes in translating
them to large brain, and in particular human, applications [7] First, silicon is fragile,
making the electrodes prone to fracture, which makes them risky for human applications.
Furthermore, the silicon microfabrication process is impractical for making large devices,
limiting commercially available probe length to around 20mm, which is too short for most
clinical applications in the human brain. Also, the connection between the electrode contacts
and the pre-amplifier in the currently available products requires a rigid circuit board that
is attached to the electrode, which is difficult to work with and which requires that the
pre-amplifiers to be kept very close to the brain. While there are FDA approved version of
silicon probes (i.e. the Utah Array used for brain machine interfaces), these applications
are limited to short <2mm long probes used for surface cortical recordings. The inherent
material and process limitations described make it unlikely that silicon-based probe
technologies will provide a clinically usable probe for deeper locations in the human brain.
The investigators, therefore, sought to utilize a new kind of translatable technology for
clinical use.
The investigators seek to test a more robust and reliable technique for recording large
numbers of single neurons in the human brain. Diagnostic Biochips Inc. (Glen Burnie, MD) is
an electrode manufacturer that has developed a new type of electrode that consists of a
stainless-steel shaft and an array of polyimide based high density electrodes that are
embedded onto this shaft. This type of electrode design has proven highly reliable for deep
brain penetrations of up to of up to 8cm length in rodent and non-human primate. The steel
carrier is highly robust, entirely avoiding the breakage problems associated with silicon
based and other high-density probe designs. Similarly, the polyimide-based electrodes are a
material that is well known to not be biotoxic, which is well tolerated and part of numerous
currently FDA approved products. The DBC Deep Array electrode is wired directly to an Intan
(Los Angeles, CA) microprocessor mounted at the other end of the shaft. This microprocessor
generates a digital signal, so that a long connection can be utilized between the
microprocessor and Intan amplifier unit used to record the data, without any loss in signal
or addition of noise. This feature is crucial to improve patient safety and reduce any
infection risks during recording. Steel is rigid, and not prone to fracture like silicon. In
addition, this type of electrode can be made significantly longer, simply by using a longer
stainless-steel shaft to mount the high-density polyimide array on. While the currently
manufactured DBC deep arrays used in animal research are 40-80 mm in length, a length of up
to 300 mm is easily feasible. This contrasts with the maximal 10 -20 mm length that is
achievable for silicon-based and other high-density systems. A length of >100mm is required
for probing deep brain structures such as the basal ganglia in the human brain, which is
routinely done in clinical settings. The DBC electrode can record up to 1024 individual
channels simultaneously. The DBC devices have been used successfully in nonhuman primates and
have undergone the biocompatibility, cytotoxicity, sterilization, and safety testing expected
for use in humans. The results of these tests were all a pass, and the resulting reports are
attached to this protocol.
