Dorsal Root Ganglion (DRG) is a novel target of neuromodulation that's use has grown as a
proven effective treatment in chronic painful conditions. Studies examining tonic,
paresthesia-based dorsal column stimulation have demonstrated plateauing or diminishing
effects after extended time periods. Although not yet studied in DRG stimulation due to
its relative infancy, the possibility of decreased pain relief over time very much
exists. In order to mitigate the potential for waning pain relief over time, other
paradigms of stimulation within the framework of DRG therapy must be evaluated.
Intermittent dosing (ID) refers to the cycling of stimulation, in which there is a
designated time period of stimulation being active (ON) and inactive (OFF). Previous
studies have demonstrated the safe and effective use of intermittent dosing using spinal
cord stimulation (SCS).9,10 In 2020, Deer et al. reported the efficacy of intermittent
dosing of Burst stimulation with settings ranging from 30 seconds ON and 90 seconds OFF,
to 30 seconds ON and 360 seconds OFF in SCS.10 However, no studies have examined the use
of ID in DRG stimulation. Furthermore, a pre-clinical study by Chao et al. 2020 showed
that DRG field stimulation delivered at 20 Hz continuously abated transmission of action
potentials in most C-type fibers and 50% of Aδ fibers. Conversely, DRG field stimulation
delivered at 5 Hz consistently evoked action potentials in Aβ, Aδ, and C type fibers,
suggesting that this frequency may have greater potential to mitigate pain11.
Nevertheless, translation of these results to clinical practice have yet to be studied.
Patients with chronic pain secondary to CRPS or other chronic neuropathic who have
responded to DRG stimulation originally and have undergone permanent DRG stimulator
implantation delivered by the Abbott PROCLAIM Dorsal Root Ganglion Neurostimulator
System, have had the system in place for at least 1 year, utilizing continuous tonic
therapy, reporting minimum 50% pain relief in the targeted area, will be randomized to 1
of 2 study arms, in a single-blinded, 1:1 fashion:
High ID Arm: DRG stimulation therapy at 20 Hz frequency for 30 seconds ON, 90
seconds OFF
Low ID Arm: DRG stimulation therapy at 5 Hz frequency for 30 seconds ON, 90 seconds
OFF
Based on the stimulation frequency each patient receives the stimulation amplitude will
be adjusted accordingly to remain in the therapeutic dosing window for each patient.
Patients will be seen and evaluated prior to randomization and reprogramming, and
thereafter evaluated at 4, 8, and 12-weeks. At the 12-week time period, patients will
begin a 1-week washout period of continuous stimulation at their pre-study stimulation
settings. At the 13-week time period, patients will be evaluated, crossed over to the
other study arm and thereafter evaluated at 17, 21, and 25-weeks.
As our primary endpoint, we hypothesize that intermittent dosing with either 20 Hz
frequency (high) or 5 Hz frequency (low) ID will provide superior pain relief as measured
by VAS scores when compared to continuous DRG stimulation therapy in this patient
population. Other endpoints include: EQ-5D scores of wellbeing; PROMIS score for physical
function, pain interference, sleep disturbance, and emotional distress; chronic pain
acceptance questionnaire 8 (CPAQ-8), patient satisfaction scores, and patient global
impression of change.
After evaluation, all eligible and consented subjects will be randomized into one of two
treatment groups. Randomization will be performed using a computer-generated random
sequence generator with equal selection probabilities to all groups. Subjects will be
blinded to their randomization.
After randomization, each consented subject will present to clinic at which time will
first be seen by a team of investigators, sub-investigators, and/or study staff. Patients
will be sent for x-ray at initial presentation to evaluate for real-time DRG lead
position. Patients will be excluded from study if there is significant migration, at the
discretion of clinician. Patients will have had at least one prior attempted
reprogramming in standard fashion (increasing amplitude firing in tonic stimulation to
document stimulation is targeting dermatome of initial placement) before enrollment in
this study. Otherwise, after evaluation and collection of baseline data, a clinical
specialist for the Abbott PROCLAIM Dorsal Root Ganglion Neurostimulator System will
program the subject's DRG system according to the treatment group to which they have been
randomized, under direct physician supervision and with use of the radiographic films.
Patient will be subsequently evaluated at 4, 8 and 12 weeks. At the 12-week time
interval, the patient will begin a 1-week washout period of continuous stimulation. At
the 13-week time interval, the patient will be crossed over to the alternative study arm.
Thereafter, they will be evaluated again at the 17-week, 21-week, and 25-week time
interval. At each interval, the patient will be evaluated by a team of investigators,
sub-investigators, and/or study staff to administer questionnaires and collect data.
Patient specific data to be collected prior to first allocated dosing stimulation will
include:
Data to be collected at baseline and at 12, 13 and 25 weeks of stimulation only:
Patient Health Questionnaire (PHQ-8)
PROMIS Health questionnaires
Global Health 10 item questionnaire
Physical Function 8b questionnaire
Emotional Distress-8a Anxiety questionnaire
Sleep Disturbance 4a questionnaire
Fatigue 8 item questionnaire
CPAQ-8 score (Chronic Pain Acceptance Questionnaire 8)
Patient Global Impression of Change (see fig. 2)
Patient Satisfaction Score (7-point Likert-type scale; see fig. 2)
Data to be collected at each study visit:
NRS pain scores (22-point scale, 0-10 in 0.5 increments)
Current dorsal root ganglion stimulation parameters (i.e. mode of
stimulation-continuous vs. ID, frequency, amplitude, pulse width)
Average charging frequency over last week
Risks & Benefits:
As with all clinical research, there exists a potential for loss of confidentiality.
Measure to protect the confidentiality of study participants will be implemented as
described in the Data Collection & Management Section Below.
Further loss of therapeutic pain relief is another potential risk that could occur
following reprogramming to ID parameters. If at any point a subject reports diminishing
pain relief and wishes to return to baseline mode of stimulation, they will be allowed to
do so and considered a study failure. Patients would be encouraged to proceed with
randomization process and if pain relief diminished, would be allowed to return to
whichever desired mode of stimulation.
Subjects may experience benefit in the form of pain relief and improved functionality
following reprogramming to ID parameters. However, if the patient chooses to no longer
participate in the study, they may still receive treatment from the treating physician,
which may include the ID parameters, administered separately, being investigated in this
study.