Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04157400 |
| Other study ID # |
00089881 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
November 26, 2019 |
| Est. completion date |
November 1, 2021 |
Study information
| Verified date |
January 2023 |
| Source |
Medical University of South Carolina |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Each year, an estimated 34,000 individuals undergo epidural spinal cord stimulation (SCS)
surgery to address debilitating chronic low back and leg pain (CLBLP). Although the
commercial application of SCS to treat CLBLP was approved by the FDA in 1989, only in the
past decade have significant advancements in stimulator technology been introduced. For
instance, traditional SCS devices achieved reduction in pain using a type of stimulation
known as low-frequency tonic stimulation (LFTS, below 100 Hz), which was dependent on
induction of paresthesias (i.e., a tingling sensation) over the areas of pain perception.
However, investigators now know that LFTS compromises sensory information flowing back to the
spinal cord, which can be important in other spinal cord functions such as proprioception and
movement. On the other hand, recent innovations in stimulator technology now provide the
capability to apply stimulation frequencies up to 10,000 Hz along with complex waveform
patterns - known as high frequency burst stimulation or HFBS - that can mitigate pain
perception without the induction of paresthesias and the negative consequences on
proprioception and movement. We propose to study the effects of these recently introduced
features in SCS technology on motor and sensory spinal thresholds, proprioception and
movement in subjects with CLBLP.
The spinal cord relies on input from the motor cortex and surrounding extremities to initiate
specific muscle recruitment, and recent evidence suggests that preservation of temporally
specific proprioceptive information via dorsal column primary afferent fibers is critical for
natural motor behaviors such as ambulation. Since the spinal cord is exposed during the
placement of the SCS device, information about a subject's motor and sensory spinal pathways
can be easily obtained during the regular course of the procedure and compared to
proprioceptive and motor responses once the subject is awake and moving with the device
turned on. Our lab specializes in electrophysiological recordings in subjects undergoing
spinal cord stimulator (SCS) implantation for CLBLP, while MUSC's Locomotion Laboratory
specializes in quantifying proprioception and movement in human subjects. In this proposal,
investigators will apply these techniques to subjects with CLBLP to determine effects of
spinal neuromodulation on motor and sensory thresholds, proprioception, and kinematics.
Description:
Definitions and nomenclature:
Spinal cord stimulation (SCS) will be performed using a 32-electrode paddle array implanted
in the dorsal epidural space along the thoracolumbar region of the spinal cord. The array
will be powered by a multiple independent current-controlled (MICC) implantable pulse
generator (IPG) connected to the paddle per standard of care procedures for SCS implantation.
In addition, as per standard of care, motor evoked potential (MEP), somatosensory evoked
potential (SSEP) and electromyography (EMG) will be performed via the IOMAX intraoperative
neuromonitoring system. The SCS system will be placed for clinical purposes, i.e., treatment
of chronic pain, however, the investigators will collect data at various points during the
placement. The study procedures will add 15 minutes to the surgery. MUSC's Locomotion
Rehabilitation Laboratory - located at the College of Health Professions Building C - houses
a Biodex Pro System 4 isokinetic/isometric dynamometer. The Biodex will standardize
application of passive isokinetic knee flexion/extension trials to each blinded subject for
proprioceptive investigations, which will be referred to as threshold to detect passive
movement (TTDPM) throughout the rest of this document. Finally, MUSC's Locomotor Energetics
and Assessment Laboratory - also located at the College of Health Professions Building C -
houses a dual belt Instrumental Treadmill that is coplanar with the floor and will be used
during all walking events. The laboratory also has a 12-camera motion capture system that
utilizes active infrared LED tracers to track kinematic positioning data and will be used
during all walking events. Another tool offered by the lab is a 16-channel EMG system which
utilizes surface electrodes to detect target muscle activity and will also be used during all
walking events. In all, expected total duration of the study to be approximately 30 days.
Device use:
The epidural stimulator paddle and IPG are FDA-approved, commercially available devices
designed to treat chronic pain of the back and lower extremities and will be used for their
intended clinical purpose - electrical stimulation of dorsal column fibers to mitigate pain
perception. The research use of this device, which will add approximately 15 minutes to the
surgery, involves recording/stimulating from the device during the standard of care
intraoperative neuromonitoring protocol. Regardless of study participation, the stimulator
paddle and IPG will be implanted according to standard of care for the pre-planned SCS
surgery. The IOMAX intraoperative neuromonitoring system, equipment owned by MUSC and
operated by MUSC neurophysiology staff, is a commercially available device used during
standard of care spinal surgical procedures, such as SCS implantation. Regardless of study
participation, intraoperative neuromonitoring via IOMAX will take place according to standard
of care for the pre-planned SCS surgery. The following devices are used for research purposes
only. The Biodex Pro System 4, used regularly by physical rehabilitation researchers here at
MUSC, is a commercially available device that will be used solely as a research tool to
deliver passive isokinetic knee flexion/extension during the TTDPM. The Instrumental
Treadmill, GAITRite mat, motion capture system, and MA300 EMG system are all commercially
available devices that are used by MUSC researchers at the College of Health Professions to
perform extensive gait analysis in subjects with various neurological deficits. Gait analysis
is being performed for research purposes only, and is not standard of care for patients
receiving SCS surgery.
Number of Subjects:
Investigators propose to study 5 individuals with CLBLP. A prior study conducted by Formento
et al, 2018 using SCS and proprioceptive testing published a standard error and 95%
confidence interval using successful and unsuccessful SCS trial attempts (p < 0.05 among LFTS
parameters and no stimulation, with a minimum of 10 trials per stimulation setting.) Based on
this, investigators expect that a small population will exhibit similar variance. The subject
sample size is in direct comparison to sample sizes of previous proof of concept studies
regarding SCS for spinal cord physiology biomarker sampling. The research team plans to use a
two-way repeated measures ANOVA model in order to investigate the varying differences in
stimulation type and kinematic parameters. A Post hoc comparison will be made using a Tukey
adjustment.
Recruitment Methods:
During the subject's preoperative clinic visit, the PI will ask the potential participant if
they would like to learn more about the study. If so, the PI will introduce the study and ask
if he can answer any further questions about the study before inviting in the PI's physician
assistant (listed as a study team member). If not, the PI will leave the room and the PI's
physician assistant will review a prescreening checklist to determine whether subjects may be
eligible for the study (no information obtained during the prescreening will be documented as
research data). Potential participants will be asked to confirm that they are between the
ages of 18 and 80, that they have been previously diagnosed with CLBLP by a pain specialist,
whether they feel they cannot provide research consent physically and/or cognitively, and
whether they have any prior history of spinal neoplasm, infection, arteriovenous malformation
and/or radiation to the spine. If potential participants answer no to either of the first two
questions or yes to either of the remaining questions, they will be considered ineligible for
the study.
Careful attention will be placed on good communication. It will be emphasized that
participation in the study is not necessary for standard of care medical treatment for their
condition. It will also be emphasized that the subject can withdraw from the study at any
time.
Data Management:
Once a potential participant is asked if they would like to learn more about the study, they
will be assigned a participant ID. Participant IDs will be assigned consecutively.
Investigators will maintain a database that accurately reflects all potential subjects that
were approached about the study and the results of eligibility evaluation. For eligible
subjects, the specific types of data that will be collected include: 1) analog local field
potentials from the SCS, MEP, SSEP and EMG electrodes, 2) digital and analog output signals
from the IOMAX intraoperative neuromonitoring device, 3) digital, time-stamped, physical
displacement data captured from the Biodex machine, 3) digital, time-stamped, positioning
data produced by the PhaseSpace software, 5) videography data, and 6) any available imaging
data (dicom files). Raw data will remain on lab-owned data acquisition machines with
encrypted hard drives and stored behind a locked door when not directly supervised. Data will
be copied from all lab-owned data acquisition machines and/or hospital-owned data servers to
a password protected network server accessible from the lab under the IRB protocol number and
participant ID. This will constitute the master copy of all data for the lab and will consist
of separately stored coded and identifiable folders. The purpose of keeping a copy of the raw
data is in case the server is interrupted, and it is necessary to reconstruct the data.
Portions of data will be copied to end-user devices (e.g., desktop, laptop, etc) for data
analysis, however only the portion needed for analysis will be copied. Any end-user device
such as a laptop that physically leaves the lab will be encrypted with MUSC-approved software
which uses the AES encryption algorithm in cipher block chaining or XTS mode with a 256-bit
key. Desktop machines used for analysis that do not leave the lab and are stored in a locked
laboratory will not be encrypted. All data on data acquisition and end-user devices will be
deleted at the conclusion of the study. No PHI will be stored on any data acquisition machine
or end-user device. A linking database associating the participant ID and subject identifiers
will be maintained on MUSC Box, separately from the research data. Subject identifiers to be
collected include first and last name, gender, date of birth, social security number, medical
record number, mailing address and telephone numbers. Telephone and medical record numbers
are required for an approximate 7-day phone call made to subjects following SCS implantation.
Additionally, investigators will collect information pertaining to disease severity for each
subject, including Visual Analog Scale (VAS) scores, a common pain scale, and any other
available rating scale scores. These measures will assist in correlating our physiological
data with severity of disease for each subject. Videography data will be stored in the
identifiable folder on the password protected network server. The purpose of this data is to
correlate movement dynamics with physiology data. Finally, investigators will save imaging
data on a password protected network server in order to analyze and correlate with the
collected physiological data. Only IRB-approved personnel will have access to the linking
database. Consent forms will be stored in a locked cabinet in a locked laboratory in the
Clinical Sciences Building at MUSC.
Risks to Subjects:
All procedures will follow standard of care guidelines. Research staff will follow up with
each participant by phone approximately one week after the surgical procedure, and during the
approximate 30-day return, to make sure the participants are not having any problems.
Nevertheless, this study still poses certain risks as outlined in the following sections:
Surgical complication
Due to the 15 extra minutes added to the surgery, connection of the paddle terminals outside
the surgical field, and extra personnel in the room, there is a slightly increased risk of
surgical infection. The extra risk of infection due to the research protocol does not
increase this risk beyond the 1-5% overall historical risk of complications from the SCS
surgical procedure.
TTDPM
While testing for proprioception retention of the lower extremities, subjects may encounter
discomfort due to non-volitional muscle activation that hinders passive movement. To mitigate
this risk, the Biodex system has a subject-controlled trigger that immediately stops the
dynamometer's passive motion and may be activated at any time a subject experiences
discomfort of pain during the test.
Overground and Treadmill Walking
Subjects will be asked to walk on a pressure sensitive mat at self-selected walking speeds
and on a treadmill at self-selected walking speeds with each scenario having the subject in
an upper thoracic safety harness which is tethered to the ceiling for fall protection.
Despite the aforementioned safety measures, there still exists a risk of loss of balance,
fall and potential injury. The risk to subjects through these tasks do not exceed risks
involved with general physical therapy settings and may result in mild muscle fatigue or
discomfort that generally subsides within a few days. Subjects will be given ample rest time
and may have additional rest time at any point throughout data collection periods.
Furthermore, subjects will be assisted during large movements or during potential transfers
across different surfaces by an IRB-approved study member.
Photography and videography
Subjects will be videotaped during performance of supine / walking SCM and EMG moduling
protocols. Investigators will also photograph and/or videotape any other aspect of the
subject's research participation that will help investigators correlate the subject's
condition with the EMG and kinematic data. The videos and photos recorded can include the
full face, upper body, arms, and legs. Photography and videography carry a risk of loss of
privacy. Photos and videos will be stored on a secure server. Only approved study personnel
will have access to these files.
Loss of Confidentiality
Additional risks include loss of confidentiality. To mitigate this risk, a linking database
associating the participant ID and subject identifiers will be maintained separately from the
research data on a password protected server and only IRB-approved personnel will have access
to the linking database.
