Coordinated Reset Spinal Cord Stimulation

The goal of this study is to evaluate whether a new spinal cord stimulation paradigm, called Coordinate Reset (CR) Stimulation, can provide equivalent or better pain relief with reduced energy requirements. The investigators will test this new stimulation paradigm in patients who are already undergoing spinal cord stimulation surgery. The investigators will also study whether there are changes in electroencephalography (brain waves) associated with this new stimulation paradigm.

The investigators hope to learn whether CR stimulation can provide equivalent or better pain relief with reduced energy requirements. They also hope to learn whether there are changes in brain function with effective CR stimulation compared to conventional stimulation.

This study will be testing a specific stimulation paradigm in people who have already consented to have spinal cord stimulation performed for treatment of their chronic pain.

Study Overview

• Status: Withdrawn
• Conditions: Failed Back Surgery Syndrome; Pain, Neuropathic
• Intervention / Treatment: Device: Coordinated Reset spinal cord stimulation

Detailed Description

Study subjects will be identified from the pool of candidates for spinal cord stimulation (SCS) therapy at Stanford University. Subjects will have undergone a successful trial of Boston Scientific spinal cord stimulation and will either be candidates for permanent stimulator implantation, or will have already undergone implantation. Ten subjects will be recruited over a one year period.

Following informed consent, subjects will be assessed to assure that they meet the criteria for study entry. All subjects will undergo SCS implantation and will be optimized on standard SCS (sSCS) settings using the standard clinical protocol, including paresthesia mapping, threshold finding, and adjustment of stimulation parameters to provide reduction in pain. Therapeutic sSCS will be maintained for a minimum of one month prior to baseline assessment.

Baseline assessments will be conducted following discontinuation of SCS for 24 hours. This assessment battery includes a physical and neurological exam, visual analog scale (VAS) score, Oswestry Disability Index, SF-12 and Global Assessment of Functioning, as well as EEG recordings (spontaneous EEG recording + dedicated pain-related evoked response recording). Following this baseline assessment, sSCS will be delivered for one month. Stimulation parameters will be held constant for the last 7 days of this period. During this time, subjects will use the CamNtech Pro-Diary wrist-worn data entry system to rate their back pain, leg pain and overall pain (3 questions), 3 times per day (morning, afternoon evening). The Pro-Diary allows for configurable, portable data entry as well as actigraphy.

The full assessment battery will be repeated, and the stimulator deactivated.

Following a washout period of three hours, VAS and EEG recordings will be performed. CR-SCS will be enabled by means of a firmware upgrade. Personnel from Boston Scientific will perform this upgrade. The stimulator will then be programmed to deliver CR-SCS. At the end of one month of CR-SCS (with stimulation parameters similarly held constant for the last 7 days), the assessment battery will be repeated, and VAS and EEG recordings will again be performed after a three hour washout period. Finally, a firmware downgrade will be performed by Boston Scientific Personnel, and patients will be treated with sSCS at their previous settings.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford Health Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients with chronic neuropathic lower extremity pain, without back pain, who have consented to undergo or are undergoing spinal cord stimulation (SCS)
2. Age 22 to 70
3. Fluent in English and able to independently provide consent
4. Patients treated with conventional SCS for at least 3 months prior to commencement of study, either newly implanted or already implanted.
5. Patients have pronounced pain, i.e. visual analog scale score (VAS) ≥6 and respond to conventional SCS, i.e. VAS reduction of at least 50% with SCS.

Exclusion Criteria:

1. Significant psychiatric problems, including unrelated clinically significant depression as determined by the investigator.
2. Current drug or alcohol abuse as determined by the investigator.
3. Any history of recurrent or unprovoked seizures.
4. Any significant medical condition that is likely to interfere with study procedures or likely to confound evaluation of study endpoints, including any terminal illness with survival <12 months.
5. Females who are pregnant, breastfeeding, or are of childbearing potential and planning to get pregnant during the course of the study or not using adequate contraception
6. On anticoagulation therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Coordinated Reset- Spinal Cord Stimulation; All subjects will undergo spinal cord stimulation (SCS) implantation and will be optimized on standard SCS (sSCS) settings using the standard clinical protocol, including paresthesia mapping, threshold finding, and adjustment of stimulation parameters to provide reduction in pain. Therapeutic sSCS will be maintained for a minimum of one month prior to baseline assessment. Following a washout period of three hours assessments will be performed and Coordinated Reset- spinal cord stimulation (CR-SCS) will be enabled by means of a firmware upgrade. Personnel from Boston Scientific will perform this upgrade. The simulator will then be programmed to deliver CR-SCS. At the end of one month of CR-SCS (with stimulation parameters similarly held constant for the last 7 days), baseline assessment will be repeated after a three hour washout period. Finally, a firmware downgrade will be performed by Boston Scientific Personnel, and patients will be treated with sSCS at their previous settings.

Device: Coordinated Reset spinal cord stimulation; Abnormal neuronal synchrony in terms of enhanced 4-9 Hz theta oscillations in EEG/MEG recordings appears to be an important pathophysiological finding in patients with neurogenic pain. To specifically counteract abnormal neuronal synchrony, we here set out to perform Coordinated Reset (CR)-Spinal Cord Stimulation (SCS). CR stimulation (Tass, 2003) aims at an anti-kindling, i.e. an "unlearning" or resetting of abnormal neuronal synchrony and abnormal synaptic connectivity, and, hence, long-lasting, sustained therapeutic effects that persist following cessation of stimulation (Tass & Majtanik, 2006).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain relief	Difference in mean reduction in visual analog scale (VAS) score between sSCS and CR-SCS for leg pain and / or back pain compared to baseline, with 0 indicating no pain and 100 indicating worst pain.	One month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Activity level	Use of CamNtech Pro-Diary wrist-worn data entry system to rate back pain, leg pain and overall pain (3 questions), 3 times per day (morning, afternoon evening). Patients will rate their pain on a 0-10 Visual Analog scale with 0 indicating no pain and 100 worst pain.	One month
Oswestry Disability Index, Sort Form-12	Oswestry Disability Index, Sort From-12 (also known as the Oswestry Low Back Pain Disability Questionnaire) is a 12 item short survey that measure a patient's permanent functional disability. Each section is scored on a 0-5 scale, 5 representing the greatest disability.	One month
Global Assessment of functioning Scale (GAF)	The Global Assessment of Functioning (GAF) scale is used to rate how serious a mental illness may be. It measures how much a person's symptoms affect their day-to-day life on a scale of 0 to 100, with higher scores indicating that the subject is better at handling daily activities.	One month
Electroencephalography (EEG)	EEG activity will be quantified by means theta power (4-9 Hz), with decreases in theta power related to decreased pain. Theta power will be measured pre and post treatment.	One month
Event Related Potentials (ERP)	During the EEG, we will analyzed ERPs in response to each stimuli during stimulation. Changes in amplitude (micro-volts) will be analyzed pre and post treatment. ERP activity is exploratory.	One month

Collaborators and Investigators

• Sponsor: Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2021
• Primary Completion (Actual): September 5, 2023
• Study Completion (Actual): September 5, 2023

Study Registration Dates

• First Submitted: July 12, 2021
• First Submitted That Met QC Criteria: August 2, 2021
• First Posted (Actual): August 9, 2021

Study Record Updates

• Last Update Posted (Actual): September 8, 2023
• Last Update Submitted That Met QC Criteria: September 5, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: chronic pain; neuropathic pain; spinal cord stimulation; failed back surgery syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Postoperative Complications; Pain; Neurologic Manifestations; Neuromuscular Diseases; Peripheral Nervous System Diseases; Back Pain; Neuralgia; Failed Back Surgery Syndrome
• Other Study ID Numbers: 44884

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No IPD shared outside of Stanford

Drug and device information, study documents

• 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