Comparing Long-term Effectiveness of High Frequency and Burst Spinal Cord Stimulation

• ClinicalTrials.gov Identifier: NCT03681262
• Recruitment Status: Recruiting
• First Posted: September 24, 2018
• Last Update Posted: May 5, 2022
• Sponsor: Stanford University
• Information provided by (Responsible Party): Vafi Salmasi, Stanford University

Tracking Information

• First Submitted Date: September 20, 2018
• First Posted Date: September 24, 2018
• Last Update Posted Date: May 5, 2022
• Actual Study Start Date: August 1, 2019
• Estimated Primary Completion Date: December 31, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 20, 2018)

Change in pain intensity [ Time Frame: 12 months ]

• Change from baseline in pain intensity at 12 months. Baseline pain intensity is measured at last CHOIR completion before trial, and is based on patient reported outcome in CHOIR for average pain in the week prior to completion of questionnaire.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 21, 2018)

• Patient global impression of change [ Time Frame: 12, 24 and 36 months ]
  Patient global impression of change as likert scale from 1-5
• Pain Intensity [ Time Frame: 12, 24 and 36 months ]
  Nuremical rating scale of average pain intensity from 0-10
• Function [ Time Frame: 12, 24 and 36 months ]
  NIH (National Institute of health) PROMIS (Patient reported outcomes measure information system) function in percentile
• Pain Interference [ Time Frame: 12, 24 and 36 months ]
  NIH (National Institute of health) PROMIS (Patient reported outcomes measure information system) pain interference in percentile
• Depression [ Time Frame: 12, 24 and 36 months ]
  NIH (National Institute of health) PROMIS (Patient reported outcomes measure information system) depression in percentile
• Anxiety [ Time Frame: 12, 24 and 36 months ]
  NIH (National Institute of health) PROMIS (Patient reported outcomes measure information system) anxiety in percentile

Original Secondary Outcome Measures (submitted: September 20, 2018)

• Patient global impression of change [ Time Frame: 12, 24 and 36 months ]
  Patient global impression of change as likert scale
• Pain Intensity [ Time Frame: 12, 24 and 36 months ]
  Nuremical rating scale of average pain intensity
• Function [ Time Frame: 12, 24 and 36 months ]
  NIH (National Institute of health) PROMIS (Patient reported outcomes measure information system) function
• Pain Interference [ Time Frame: 12, 24 and 36 months ]
  NIH PROMIS pain interference
• Depression [ Time Frame: 12, 24 and 36 months ]
  NIH PROMIS depression
• Anxiety [ Time Frame: 12, 24 and 36 months ]
  NIH PROMIS anxiety

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Comparing Long-term Effectiveness of High Frequency and Burst Spinal Cord Stimulation
• Official Title: Comparing Long-Term Effectiveness of High Frequency and Burst Spinal Cord Stimulation
• Brief Summary: Over 100 million Americans suffer from chronic pain resulting in annual cost of roughly $635 billion. Limited treatments are available for this widespread disease. The data supporting these treatments lack generalizability to patients with more serious medical and psychological comorbidities who are often excluded from explanatory efficacy trials. This study aims to integrate randomized comparative effectiveness research with patient care. The investigators will randomize the patients and collect data using an open-source learning healthcare system already in use in the department to monitor patients' progress: Collaborative Health Outcomes Information Registry (CHOIR). CHOIR uses the National Institute of Health Patient Reported Outcomes Measurement Information System item banks for comparative metrics through computer adaptive testing. The investigators will leverage the advantage of this novel system to compare effectiveness of high frequency and burst spinal cord stimulation in improving pain and function in patients with chronic back and/or leg pain. Spinal cord stimulation is an effective treatment for chronic pain resulting in >50% pain relief in about half of the patients. Novel waveforms for spinal cord stimulation - high frequency and burst - increased the efficacy of this treatment even further. However, there is lack of data guiding decision making of the clinicians in choosing the best waveform in treating the patients with chronic pain. The proposed study will provide the clinicians with this evidence. Currently, data about safety and efficacy of these two novel waveforms is available for up to 24 months. The proposed research will provide data about effectiveness of these two modalities for at least 36 months. Moreover, this study will evaluate feasibility of integrating randomized comparative effectiveness research with patient care in Stanford Pain Management subspecialty clinic. CHOIR can then be applied for numerous future trials to advance knowledge in perioperative and pain medicine.

Detailed Description

Specific Aims:

The investigators are proposing to compare the effectiveness of high frequency and burst spinal cord stimulation in patients with chronic back and/or leg pain.

More than one hundred million Americans suffer from chronic pain with estimated annual cost of $635 billion.1 To better characterize these patients, Stanford Pain Management Center has implemented a patient reported registry, Collaborative Health Outcomes Information Registry (CHOIR), since 2012. CHOIR surveys include National Institute of Health (NIH) Patient Reported Outcomes Measurement Information System (PROMIS) item banks, a body map, questions about pain intensity, pain catastrophizing scale, and questions about patients' pain experience and healthcare utilization. This learning healthcare system also has the capability of point-of-care randomization.

Spinal cord stimulation is one of the most effective treatments for patients with intractable trunk and limb pain. Traditional tonic spinal cord stimulation resulted in at least 50% pain reduction in about half of the patients.2,3 Newer waveforms - high frequency and burst - achieve 50% pain reduction in 60-75% of the patients in comparison.4-6 However, more studies are needed to compare effectiveness of these two new waveforms.

The investigators are proposing to use patient reported outcomes to conduct a pragmatic clinical trial that integrates with patients' clinical care; thus, allowing faster recruitment of a larger patient cohort. The patient's provider will use CHOIR point-of-care randomization to randomly assign patients to either receive high frequency or burst spinal cord stimulation. The patients will then complete online CHOIR surveys sent out to them at baseline and then 1, 3, 6, 12, 18, 24 and 36 months after their device implant. These surveys will include PROMIS item banks for pain interference, function, depression and anxiety; questions about pain intensity; and questions about any potential side effects. The investigators will include patients with chronic (pain for at least 6 months) back and/or leg pain refractory to conventional management.

Specific Aim 1: Comparing effectiveness of high frequency and burst spinal cord stimulation in improving pain, function and pain interference in patients with chronic low back and/or leg pain persistent more than 6 months.

The investigators hypothesize that high frequency spinal cord stimulation is more effective than burst spinal cord stimulation in decreasing chronic low back and/or leg pain.

The investigators' primary outcome is change from baseline in pain intensity at 12 months. The investigators will also compare improvement in function and pain interreference at all follow up time points. The investigators will plot the trend of all these measures and study change from baseline at 12 months. The investigators will use repeated measure linear regression to compare these measures between the groups at follow up time points with time as the fixed effect and treatment as random effect.

Specific Aim 2: Comparing effectiveness of high frequency and burst spinal cord stimulation in improving depression and anxiety in patients with chronic low back and/or leg pain persistent more than 6 months.

The investigators hypothesize that high frequency spinal cord stimulation is more effective than burst spinal cord stimulation in decreasing stress and anxiety in patients with chronic low back and/or leg pain.

Burst stimulation modulates medial thalamic pathway, which attributes adverse emotions to pain. The investigators will therefore compare emotional response to these waveforms. The investigators will compare change from baseline of depression and anxiety at 12 months. The investigators will also plot depression and anxiety trend at all follow up time points between two groups using repeated measure linear regression. The investigators will then perform a similar stratified analysis in responders (patients with 50% or more pain reduction at 1 year) and non-responders to these treatments; this analysis is to asses if pain reduction is an effect measure modifier in this relationship.

• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Randomized open label parallel group

Masking: None (Open Label)
Primary Purpose: Health Services Research

• Condition: Chronic Pain

Intervention

• Device: High frequency spinal cord stimulation
  We will use Senza® (Nevro Corp., Palo Alto, CA) trial and implant systems to deliver high frequency spinal cord stimulation. A trial system includes two trial leads, an external pulse generator, and a remote control. The permanent implant system includes two leads, an internal pulse generator, a remote control, and a charging device for internal pulse generator. We will use our routine process of trial and implant. High frequency waveform will be delivered with following parameters: frequency of 10,000 hertz, pulse width of 20 microseconds, and amplitude of 0-15 milliamperes.
• Device: Burst spinal cord stimulation
  We will use BusrtDRTM (Abbott Saint Jude Medical, St. Paul, MN) trial and implant systems to deliver burst spinal cord stimulation. A trial system includes two trial leads, an external pulse generator, and a remote control. The permanent implant system includes two leads, an internal pulse generator, a remote control, and a charging device for internal pulse generator. We will use our routine process of trial and implant. The parameters of the stimulation are as below: each burst includes 5 pulses of electrical stimulation at intra-burst frequency of 500 hertz without time for discharge in between pulses. These bursts will be repeated at inter-burst frequency of 40-60 hertz. The amplitude will range between 0 and 15 milliamperes.

Study Arms

• Experimental: High frequency spinal cord stimulation
  Implant of the device that can deliver high frequency waveform to spinal cord
  Intervention: Device: High frequency spinal cord stimulation
• Experimental: Burst spinal cord stimulation
  Implant of the device that can deliver burst waveform to spinal cord
  Intervention: Device: Burst spinal cord stimulation

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 20, 2018): 160
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2026
• Estimated Primary Completion Date: December 31, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Adult English-speaking patient 18 years old or above
2. Persistent pain in lower back and/or leg for more than six months
3. Candidate for spinal cord stimulation (with either high frequency or burst waveforms) based on recommendations from Stanford Pain Management Center Neuromodulation Multidisciplinary Team Conference.

Exclusion Criteria:

1. Motor weakness in neurological examination in lower body based on the assessment by treating pain physicians
2. Previous failed spinal cord stimulation trial with either high frequency or burst waveforms
3. Patient refusal

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Vafi Salmasi, MD.; 6507250246; vsalmasi@stanford.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03681262
• Other Study ID Numbers: 47965
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Vafi Salmasi, Stanford University
• Original Responsible Party: Vafi Salmasi, Stanford University, Instructor
• Current Study Sponsor: Stanford University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Vafi Salmasi, MD.; Stanford University

• PRS Account: Stanford University
• Verification Date: May 2022