Clinical trial NCT03852381: Mechanisms and Outcome-Prognostication for Paresthesia-based and -free Spinal Cord Stimulation
Official title: Mechanisms and Outcome-Prognostication for Paresthesia-based and -free Spinal Cord Stimulation in Patients with Persistent Neuropathic Pain: the MOPPStim Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Neuropathic Pain
Chronic Pain
Keywords: Spinal Cord Stimulation
Burst Stimulation
High Frequency Stimulation
High Density Stimulation
fMRI
MEG
QST
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: MSH-UHN AMO Innovation Fund
First posted: 2019-02-25
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Spinal cord stimulation (SCS) relies on stimulation of pain-relieving pathways in the spinal cord to treat chronic neuropathic pain. Traditional paresthesia-based SCS (PB-SCS) relies on providing analgesia through stimulation of spinal cord dorsal columns but it is often associated with attenuation of analgesic benefit and lack of acceptance of paresthesias. Recently introduced three different paresthesia-free (PF-SCS) modes of stimulation aim to overcome limitations of PB-SCS. Several questions regarding PB and PF SCS modes remain unanswered including the mechanisms of therapeutic benefit, criteria for selecting patients likely to benefit, and long-term outcomes. A concerted effort is required to understand and optimize utilization of SCS. This project has the twin goals of using neuroimaging techniques to understand mechanisms that underlies analgesic benefit from PB/PF-SCS modes and to identify criteria for selecting patients based on monitoring of pain and its related domains in patients undergoing SCS trials. Achieving these objectives will increase probability of analgesic benefit while minimizing adverse effects and knowledge gains from this study will be applicable to other therapies for chronic pain conditions.

Detailed description: Over 7 million Canadians suffer from chronic pain with 1 in 4 patients having neuropathic pain (NP), a condition caused by injury to nerves in the body. NP tends to have an extremely unpleasant character, severe intensity, and a persistent unremitting course. Conventional medical management (CMM) is often ineffective in relieving NP in majority of these patients. Paresthesia-Based Spinal Cord Stimulation (PB-SCS) has been used to treat NP but it has limitations in terms of preserving analgesic benefit and it is often associated with adverse effects. Recently introduced Paresthesia-Free SCS (PF-SCS), available at all tertiary level pain centers, has the potential to overcome these limitations but knowledge gaps remain in understanding and applying this modality.

The study design will be a prospective, exploratory study with randomization of order of no stimulation with novel modes of PF-SCS during the SCS trial and blinding of subjects (as per clinical standard of care) and outcome assessors. Participants with appropriate indications for trial of SCS with novel paresthesia-free modes will be enrolled. Baseline demographic and pain-related data including opioid intake in Oral Morphine Equivalents Per day in mg (OMED) will be collected. Pre-SCS trial neuroimaging (fMRI, MEG) and QST will be performed to establish parameters for future comparisons. Data on physical activity and sleep will be collected using actigraphy, as per standard of care. Data on pain and its related domains will be collected using validated questionnaires on the Manage My Pain app, in which all questionnaires administered are part of the patient's clinical standard of care. Ninety subjects will undergo a percutaneous trial of SCS that will last 12 days and the trial will be divided into three phases. All subjects will trial a conventional paresthesia-based SCS mode in the first four days of the trial. Subjects will then proceed the next four days (day 5-8) with no (placebo) stimulation, followed by one of the three novel PF-SCS modes (Burst, High Frequency, High Density) for the last 4 days of the trial. This process is currently adopted for all patients receiving SCS as standard of care. Neuroimaging (fMRI, MEG) and QST will be performed at the end of the SCS trial. Subjects who achieve significant reduction in pain, disability and sleep disturbance questionnaire scores with one of the novel PF-SCS modes will be offered percutaneous implantation of SCS system 4 to 6 weeks after the end of the trial using the novel PF-SCS mode they experienced during the trial. MEG and QST will be performed and data from validated questionnaires on the Manage My Pain app will be collected at 6 months after implantation.

Use of fMRI (functional Magnetic Resonance Imaging), MEG (Magnetoencephalography), and QST (Quantitative Sensory Testing) in this study will help improve understanding of the alteration in brain in NP and the analgesic action of PB/PF-SCS. Validation of wearable technology and of app-based digital platforms will allow these available but infrequently-used modalities to improve success of analgesic treatments in patients with chronic pain. Healthcare systems will benefit through efficient use of resources to treat chronic pain made possible by understanding what works, who does it work for, and how to predict analgesic benefit.

Eligibility criteria: Inclusion Criteria:

1. Adults, 18 - 80 years of age, with refractory neuropathic pain (as per clinical features and DN4 score \> 3/10) in back and or lower limbs for more than 3 months following lumbar spine surgery
2. Severity of pain \> 3/10 on NRS and ODI score for disability \>40/100; and
3. Pain refractory to conventional medical management tried for at least 3 months.

Exclusion Criteria:

1. Age \< 18 or age ≥ 80 years;
2. Previous trial or implantation of SCS system;
3. Procedural contraindications to SCS including extensive thoracolumbar spine surgery, moderate-to-severe central canal stenosis, coagulopathy, local or systemic infection;
4. Pregnancy;
5. Opioid dose \> 200 mg OMED;
6. Psychiatric or psychological disorder likely to impact perception of pain;
7. Inability to comply with the study interventions or evaluate treatment outcomes;
8. Mechanical spine instability as per flexion/extension lumbar X-rays;
9. Ongoing litigation issues related to the pain; and
10. Concomitant peripheral neuropathy or myopathy or central neuropathic pain (e.g. post-stroke pain).

Primary outcomes:
measure: Changes in neuronal activity with the novel PF-SCS modes as detected by fMRI and MEG
timeFrame: 12 days after the initiation of the SCS trials )
measure: Changes in neuronal activity with the novel PF-SCS modes as detected by fMRI and MEG
timeFrame: 6 months after the initiation of the SCS implants
measure: To measure long-term outcomes of novel PF-SCS modes including intensity and quality of pain, physical and psychological functioning, and patients' global impression of change
timeFrame: 6 months after the initiation of the SCS implants.
measure: Changes in sensory threshold with the novel PF-SCS modes as detected by QST
timeFrame: 6 months after the initiation of the SCS implants
Secondary outcomes:
measure: To measure incidence of more than 50% reduction in pain intensity scores in patients with NP syndromes with novel modes of SCS
timeFrame: Six months after implantation.
measure: To correlate data on physical activity as measured by an accelerometer during trials of novel SCS modes with data obtained from validated questionnaires
timeFrame: 12 days after the initiation of the SCS trial
measure: To correlate data on sleep as measured by an accelerometer during trials of novel SCS modes with data obtained from validated questionnaires
timeFrame: 12 days after the initiation of the SCS trial
measure: To measure incidences of analgesic failure (as indicated with less than 50% reduction in pain intensity scores) and adverse effects of PF-SCS
timeFrame: Six months after implantation.
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Toronto Western Hospital
state: Ontario
Study officials:
affiliation: University Health Network, Toronto
name: Anuj Bhatia, MD FRCPC
role: PRINCIPAL_INVESTIGATOR
References: