The DRG-STIM Study: Spasticity and Postural Stability after Long-Term Dorsal Root Ganglion (DRG)-Stimulation: A One-Year Safety and Preliminary Efficacy Study in 10 Patients with Spinal Cord Injury (SCI)

Dorsal Root Ganglion (DRG) stimulation is a currently available treatment
modality proven to be effective in its application for chronic pain. In a
previous pilot study (MEC2017-107) performed by our research group, we
demonstrated that DRG stimulation is also able to evoke both isotonic and
isokinetic motor responses in patients with Spinal Cord Injury (SCI).
Additionally, we observed beneficial stimulation-induced secondary health
effects. This included a decrease in severity and frequency of spasticity, and
an improvement of postural stability as reported by a number of patients. Both
secondary effects are considered to have a larger impact on a patient*s quality
of life (QoL) as compared to treatments involving regain of locomotion. Based
on these findings, we intend to further assess the particular efficacy as well
as the safety of long-term DRG stimulation in patients with chronic SCI for
these secondary health effects.

The primary aim of this case series is to investigate the safety and efficacy
of long-term DRG stimulation in reducing spasticity in patients with motor
complete and incomplete SCI. The secondary aim concerns improving postural
stability through stimulation as well as positively affecting a number of other
secondary health outcomes, namely, functional independence, pain, bladder and
bowel function, sexual function, and quality of life.

Prospective case series

The invasive interventions in the study consist of:
1) Surgical placement of max. 8 DRG-leads (under local anesthesia) for a trial
phase (2 weeks)
2) After 2 weeks of trial phase: surgical removal of surplus DRG-leads (under
local anesthesia). Max. 4 of the most effective DRG-leads will be left in situ
and connected to a subcutaneously placed IPG (battery).

Prior to inclusion in the study period, the patients will be subjected to a
screening consisting of medical history, neurological and neurophysiological
tests (e.g. H-reflex) and a MRI. The MRI will contribute to determining a
priority list of reachable and stimulateable DRGs associated with the
spasticity-related myotomes and/or dermatomes. If <2 levels are expected to be
implantable based on the MRI, the patient will have to be excluded.

After inclusion in the study period the patient will be subjected to the
following contact- and measurement points:
After inclusion of the patients an initial baseline measurement (B0) will be
conducted to assess current spasticity, postural stability and secondary health
factors. Then, the patient will undergo the first surgical procedure where a
maximum of eight temporary DRG leads will then be surgically placed on the
DRG-levels expected to be most successful. On the same day of surgery (in the
afternoon), the patient will be subjected to EMG-measurements under supra-motor
threshold stimulation on different (combinations of) DRG-leads with the purpose
of determining the dermatome coverage of every lead (C1).

The patient then starts the two-week trial phase, during which a maximum of
four leads deemed most effective are identified and stimulated with an external
pulse generator (EPG). If deemed necessary, there are two moments for the
stimulated leads or stimulation parameters to be optimized during this phase
(O1 and O2). After these two weeks, should the patient show a minimally
clinically important difference in spasticity, the internal phase will commence
with surgical removal of all surplus leads and connection of a maximum of four
most optimal leads to a subcutaneous battery (IPG) placed permanently. A second
baseline measurement (B1) will follow the second surgery to objectify any
changes to spasticity, postural stability, and secondary health outcomes and
will serve as a comparative baseline for both short and long term changes to
these objectives. After one month, another measurement (T1), with the same
measurements as in B1, will take place. This is followed by a stim-off period
in which the DRG stimulator will be switched off for two weeks as an internal
control and evaluation of the carry on effects of the stimulation. The
stimulator will then be turned back on to previously defined parameters and
over the next 10 months, three more in-house measurements (T2-T4) and two home
visits (H1-2) will be performed. After 12 months (last study follow up visit)
patients are asked whether they prefer to continue using DRG stimulation
treatment or have the system removed. All patients will then be followed in
accordance with standard medical care. This entails regular check-up
appointments at the department of Pain Medicine (outpatient clinic), in
parallel to the standard clinical protocol for DRG-devices implanted for
chronic pain. If necessary, a member of the research team can join these
appointments to advice on e.g. stimulation parameters adjustments for treatment
optimization.

This study also aims to investigate the safety of long-term DRG-stimulation
through the monitoring of (S)AEs. These will be assessed for each patient
starting from their first study treatment (implantation) to two weeks after
study completion (T4).

The Center for Pain Medicine of the Erasmus MC performs more than 30 DRG
placements annually, with low complication rates. The patients in this
long-term efficacy study will undergo two surgical procedures under local
anesthesia and will eventually keep a maximum of four permanent DRG leads,
which are subcutaneously connected to an implanted pulse generator. Risks that
may occur for patients who are implanted with a DRG device include possible
infection, bleeding, cerebrospinal fluid (CSF) leakage, numbness, and pain
below the level of the implant. During the implantation, X-rays are used to
guide the process of lead-placement. The radiation exposure of this procedure
(3 mSv) confounds to ICRP62 guidelines. These risks are considered to be
relatively low when performing the procedure in patients for the indication of
neuropathic pain. We expect the same for patients with SCI.

As part of the screening for inclusion, a lumbar MRI will be made. The
exclusion of patients with non-MRI compatible devices, as well as the relative
short imaging duration, will limit the risk and discomfort of patients during
this period. There are no risks associated with EMG measurements using surface
electrodes. None of the other clinical outcome measures are expected to pose a
risk and the frequency and duration of the questionnaires are considered to be
of moderate experimental burden to the included patients.

We conclude there are moderate risks associated with participation and the
burden can be considered moderate. However, the potential clinical implications
and symptom relief which could potentially be achieved in this patient, in our
eyes justifies the burden.*