Clinical trial NCT04709757: Comparison of Continuous and Burst High Frequency Spinal Cord Stimulation Paradigms
Official title: Intermittent Dosing of Spinal Cord Stimulation as Alternate Paradigm to Continuous 10kHz Frequency Therapy (HF10 Therapy)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Chronic Low-back Pain
CRPS
Peripheral Neuropathy
Keywords: Chronic pain
Spinal cord stimulation
CRPS
Lead sponsor: Rush University Medical Center
Sponsor class: OTHER
First posted: 2021-01-14
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Participants will be randomized to receive 1) Intermittent Dosing Therapy 30 seconds ON 90 seconds OFF or 2) Intermittent Dosing Therapy 30 seconds ON and 360 seconds OFF

Patients will be seen and evaluated prior to randomization, and thereafter at 2, 4 and 6 weeks. At the 6-week time period, patients will be crossed over to the other study arm and thereafter evaluated at 2, 4 and 6 weeks.
Primary purpose: TREATMENT

Brief summary: Spinal cord stimulation (SCS) delivered at 10kHz frequency (HF10 Therapy) has demonstrated superiority to traditional SCS for leg and back pain. 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. However, there still remains a paucity of clinical data on the use of intermittent dosing and which doses (i.e. on/off cycle time periods) are most effective. Furthermore, no previous studies have utilized HF10 therapy when evaluating intermittent dosing.

Patients with chronic back and/or leg pain who have undergone permanent spinal cord stimulator implantation delivered by the Nevro Omnia Neurostimulation System and who are reporting decreased efficacy of continuous HF10 therapy will be randomized into one of two treatments: 1) Intermittent Dosing therapy at 30 seconds ON, 90 seconds OFF 2)Intermittent Dosing therapy at 30 seconds ON, 360 seconds OFF.

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. After evaluation and collection of baseline data, a clinical specialist for the Nevro Omnia Neurostimulation system will program the subject's SCS system according to the treatment group to which they have been randomized, under direct physician supervision

Patient's will be seen and evaluated prior to randomization, and thereafter at 2, 4 and 6 weeks. At the 6-week time period, patients will be crossed over to the other study arm and thereafter evaluated at 2, 4 and 6 weeks.

As our primary endpoint, we hypothesize that ID HF10 therapy will provide non-inferior pain relief as measured by VAS scores when compared to continuous HF10 therapy. Other endpoints include: charging frequency, 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

Detailed description: Spinal cord stimulation (SCS) delivered at 10kHz frequency (HF10 Therapy) has demonstrated superiority to traditional SCS for leg and back pain. This mode of stimulation entails delivery of a greater charge per second compared to traditional tonic spinal cord stimulation and corresponding implications for battery usage. Although not yet studied in novel modes of SCS such as HF10 and Burst3 due to their relative infancy, the possibility of decreased pain relief over time very much exists. This has been well-documented with the use of tonic spinal cord stimulation. Furthermore, the most common cause of spinal cord stimulator explant remains the lack or loss of efficacy. In order to mitigate the potential for waning pain relief over time and downstream consequences of increased charge burden, other paradigms of stimulation within the framework of HF10 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. 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 this 50 subject study, 45.8% of patients preferred stimulation with 30 seconds ON and 360 seconds OFF. However, there still remains a paucity of clinical data on the use of intermittent dosing and which doses (i.e. on/off cycle time periods) are most effective. Furthermore, no previous studies have utilized HF10 therapy when evaluating intermittent dosing.

This study seeks to prospectively compare continuous HF10 therapy versus two intermittent dosing HF10 (ID HF10) therapies - 1) 30 seconds ON and 120 seconds OFF; 2) 30 seconds ON and 360 seconds OFF - in patients endorsing decreasing efficacy of continuous HF10 therapy.

We hypothesize that ID HF10 therapy will provide non-inferior pain relief as measured by NRS scores when compared to continuous HF10 therapy. The primary outcome for this study will be NRS pain scores (0 to 10 where 0 = no pain and 10 = worst pain ever in 0.5 increments). Secondary endpoints include: charging frequency, EQ-5D scores of wellbeing, PROMIS scores 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.

Patients with chronic back and/or leg pain who have undergone permanent spinal cord stimulator implantation delivered by the Nevro Omnia Neurostimulation System, have had the system in place for at least 1 year, utilizing continuous HF10 therapy, and now endorsing decreasing efficacy of continuous HF10 therapy will be randomized to 2 groups, in a single-blinded, 1:1 fashion:

1. ID HF10 therapy at 30 seconds ON, 90 seconds OFF
2. ID HF10 therapy at 30 seconds ON, 360 seconds OFF

Patient's will be seen and evaluated prior to randomization, and thereafter at 2, 4 and 6 weeks. At the 6-week time period, patients will be crossed over to the other study arm and thereafter evaluated at 2, 4 and 6 weeks.

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. After evaluation and collection of baseline data, a clinical specialist for the Nevro Omnia Neurostimulation system will program the subject's SCS system according to the treatment group to which they have been randomized, under direct physician supervision.

Patient will be subsequently seen at 2, 4 and 6-weeks in a clinic setting. At each interval, the patient will be seen by a team of investigators, sub-investigators, and/or study staff to administer questionnaires and collect data. .

Patient specific data to be collected will include:

* Age
* Height
* Weight
* BMI
* Gender
* Primary diagnosis
* Current daily morphine milligram equivalent usage

Data to be collected at baseline and at 6 and 12 weeks of stimulation:

* 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)
* Average charging frequency over last week
* Patient Global Impression of Change
* Patient Satisfaction Score

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 (see fig. 1)

Data will be collected and entered on Redcap with data access limited to research personnel. Data will be exported from RedCap™ into an Excel sheets and stored for analysis on the Department of Anesthesiology shared network folder on the Rush domain. Access to this shared resource is limited to research personnel and access is controlled using the users Rush login. The data will be analyzed on an investigators workstation that is password protected.

Eligibility criteria: Inclusion Criteria:

* Age between 18 and 90
* 1-year or more use of continuous HF10 therapy as delivered a permanently implanted Nevro Omnia Neurostimulation System for chronic back and/or leg pain
* Some level of decreasing pain relief from their SCS system (see fig. 3)
* Willing and able to complete protocol requirements, including:

  * Complete health questionnaires and pain scales as specified in the protocol
  * Sign the study-specific informed consent form
  * Complete follow-ups at the designated time periods

Exclusion Criteria:

* Previous intermittent dosing usage and/or failure
* Cervical SCS system
* Other concurrent neuromodulation system in place
* Current daily morphine milligram equivalent usage 90mg or higher

Primary outcomes:
measure: NRS pain scores
timeFrame: Up to 3 months
Secondary outcomes:
measure: Patient Satisfaction with Treatment Score
timeFrame: Up to 3 months
measure: CPAQ-8
timeFrame: Up to 3 months
measure: Current mode of stimulation
timeFrame: Up to 3 months
measure: Stimulator settings- frequency
timeFrame: Up to 3 months
measure: Stimulator settings- amplitude
timeFrame: Up to 3 months
measure: Stimulator settings- pulse width
timeFrame: Up to 3 months
measure: Charging frequency of spinal cord stimulator
timeFrame: Up to 3 months
measure: PROMIS- Fatigue 8 questionnaire
timeFrame: Up to 3 months
measure: PROMIS- Sleep Disturbance 4a questionnaire
timeFrame: Up to 3 months
measure: PROMIS- Emotional Distress- 8a Anxiety questionnaire
timeFrame: Up to 3 months
measure: PROMIS- Physical Function 8b questionnaire
timeFrame: Up to 3 months
measure: PROMIS- Pain Interference 6b questionnaire
timeFrame: Up to 3 months
measure: PROMIS- Global Health 10 item questionnaire
timeFrame: Up to 3 months
measure: PHQ-8
timeFrame: Up to 3 months
measure: Patient Global Impression of Change
timeFrame: Up to 3 months
Other outcomes:
Locations:
Study officials:
affiliation: Rush University Medical Center
name: Robert J McCarthy, PharmD
role: STUDY_DIRECTOR
References:
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