Spinal Cord Stimulation for Chronic Pain

(MOPPStim Trial)

Overseen By Anuj Bhatia, MD FRCPC

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University Health Network, Toronto

Must not be taking: Opioids

Disqualifiers: Previous SCS, Pregnancy, Psychiatric disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 12

90 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, it does mention that your pain should be refractory (not responding) to conventional medical management tried for at least 3 months, which suggests you may continue your current medications if they are not effective.

What data supports the effectiveness of the treatment Spinal Cord Stimulation for Chronic Pain?

Research shows that spinal cord stimulation (SCS) has been effective in managing chronic pain, especially neuropathic pain (pain from nerve damage), with many patients experiencing long-term relief. Additionally, transcutaneous spinal cord stimulation (tSCS) has been used to aid motor recovery in spinal cord injury patients, suggesting its potential in modulating nerve activity. ^{1 2 3 4 5}

Is spinal cord stimulation safe for humans?

Spinal cord stimulation (SCS) is generally considered safe for treating chronic pain, with long-term safety data available from real-world evaluations. However, while complications are well documented, the risk of spinal cord injury during electrode implantation is not fully known. ^{3 6 7 8 9}

How is spinal cord stimulation different from other treatments for chronic pain?

Spinal cord stimulation (SCS) is unique because it uses electrical impulses to alter pain signals before they reach the brain, which can be done through implanted electrodes (epidural) or non-invasive methods (transcutaneous). This approach is different from medications or surgeries, as it directly targets the spinal cord to manage pain without the need for drugs or destructive procedures. ^{1 3 4 10 11}

Research Team

Anuj Bhatia, MD FRCPC

Principal Investigator

University Health Network, Toronto

Eligibility Criteria

This trial is for adults aged 18-80 with chronic neuropathic pain in the back or lower limbs following lumbar spine surgery, which hasn't improved after at least 3 months of treatment. Participants should have a pain severity over 3/10 and disability score over 40/100. It's not for those with certain psychiatric conditions, pregnant women, people unable to follow the study protocol, spinal instability on X-rays, ongoing litigation related to their pain, other types of neuropathy or myopathy, previous SCS trials or implants.

Inclusion Criteria

You have had ongoing pain that hasn't improved with regular treatments for at least 3 months.

You have pain rated higher than 3 out of 10 and a disability score higher than 40 out of 100.

Adults between 18 and 80 years old who have had ongoing, severe nerve pain in their back and/or legs for more than 3 months after having surgery on their lower spine.

Exclusion Criteria

Pregnancy

You have instability in your spine that can be seen in certain X-rays.

You are currently involved in legal issues related to the pain.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

SCS Trial

Participants undergo a percutaneous trial of SCS with different modes: PB-SCS, placebo, and PF-SCS

12 days

Daily visits for 12 days

Post-Trial Assessment

Neuroimaging and psychophysical testing conducted at the end of the SCS trial

1 day

Implantation and Follow-up

Participants who respond well to the trial receive SCS implantation and are monitored for 6 months

6 months

Regular follow-up visits

Treatment Details

Interventions

• Spinal Cord Stimulation

Trial Overview The trial is testing Spinal Cord Stimulation (SCS) methods: traditional paresthesia-based (PB-SCS) and newer paresthesia-free (PF-SCS). It aims to understand how these treatments relieve pain using neuroimaging techniques and determine criteria for selecting patients most likely to benefit from these therapies.

Participant Groups

Group I: Spinal Cord Stimulation Experimental Treatment 1 Intervention

At baseline, the following data will be recorded: standard-of-care questionnaire scores, neuroimaging (fMRI, MEG), psychophysical testing (QST), accelerometer sleep and activity data. The trial will proceed as follows: Day 1-4: Paresthesia-based SCS (PB-SCS) Day 5-8: No SCS (placebo) Day 9-12: PF-SCS Neuroimaging and psychophysical testing will be conducted at the end of the trial, and will be assessed 6-months post-implantation of the SCS device along with adverse effects. A decision to implant the SCS system will be made based on reduction of patient pain intensity by 50% in PB-SCS and/or PF-SCS modes, but not with placebo SCS. Based on the response in the trial, the patient will either not be a candidate for an SCS implant, or they will receive one of the four modes upon implantation (PB-SCS, or one of the three PF-SCS: Burst, High Frequency, High Density).

Spinal Cord Stimulation is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Spinal Cord Stimulation for:

• Failed back surgery syndrome (FBSS)
• Adhesive arachnoiditis
• Peripheral causalgia/neuropathy
• Reflex sympathetic dystrophy (RSD)
• Phantom limb/stump pain
• Ischemic pain of vascular origin
• Complex regional pain syndrome
• Pain after an amputation
• Visceral abdominal pain and perineal pain

Approved in European Union as Spinal Cord Stimulation for:

• Chronic pain
• Neuropathic pain
• Spinal cord injury pain
• Failed back surgery syndrome (FBSS)
• Adhesive arachnoiditis
• Peripheral causalgia/neuropathy
• Reflex sympathetic dystrophy (RSD)

Approved in Canada as Spinal Cord Stimulation for:

• Chronic pain
• Neuropathic pain
• Spinal cord injury pain
• Failed back surgery syndrome (FBSS)
• Adhesive arachnoiditis
• Peripheral causalgia/neuropathy
• Reflex sympathetic dystrophy (RSD)

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

MSH-UHN AMO Innovation Fund

Collaborator

Trials

3

Recruited

240+

Findings from Research

In a study involving seven patients with traumatic paraplegia and chronic pain, six patients reported good to very good outcomes from epidural electrical stimulation over follow-up periods of up to six years.

The positive effects on chronic pain suggest that epidural electrical stimulation should be considered as a treatment option before resorting to more invasive surgical procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experience with spinal cord stimulation (SCS) in the management of chronic pain in a traumatic transverse lesion syndrome. Buchhaas, U., Koulousakis, A., Nittner, K.[2019]

In a pilot study involving 7 individuals with chronic spinal cord injury, the use of transcutaneous electrical spinal cord stimulation (TSCS) combined with functional training led to improvements in upper and lower extremity function, with all participants showing progress on the Capabilities of Upper Extremity Test (CUE-T).

Notably, two participants improved their ASIA impairment scale classification, and five individuals experienced enhanced sensation, demonstrating that TSCS can facilitate recovery even after a plateau in rehabilitation progress, without any serious adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Electrical Spinal Cord Stimulation to Promote Recovery in Chronic Spinal Cord Injury. Tefertiller, C., Rozwod, M., VandeGriend, E., et al.[2022]

Transcutaneous spinal cord stimulation (tSCS) shows potential for generating motor activity in individuals with spinal cord injury, but the overall quality of the studies reviewed was poor-to-fair, indicating a need for more rigorous research.

The review identified significant variability in stimulation parameters and outcome measurements across the 25 studies analyzed, highlighting the necessity for standardized methods to improve the reliability and comparability of tSCS research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous spinal cord stimulation and motor responses in individuals with spinal cord injury: A methodological review. Taylor, C., McHugh, C., Mockler, D., et al.[2022]

Cervical transcutaneous spinal cord stimulation (tSCS) can effectively activate sensory fibers at lower stimulation intensities when the cathode electrode is positioned at the C7 or T1 vertebra, compared to C6, which may enhance rehabilitation outcomes for upper-limb motor recovery after spinal cord injury.

Using smaller electrode sizes not only lowers the activation threshold for sensory fibers but also optimizes the recruitment of these fibers before α-motor fibers, suggesting a strategic approach to improve hand muscle activation during tSCS therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing sensory fiber activation during cervical transcutaneous spinal stimulation using different electrode configurations: A computational analysis. de Freitas, RM., Capogrosso, M., Nomura, T., et al.[2022]

Spinal cord stimulation has proven effective for chronic neuropathic pain, particularly in patients with peripheral nerve or posterior root lesions, where other treatments often fail.

In a retrospective study of 84 patients over 16 years, 56 continued to use their stimulators, with 72% reporting satisfactory pain relief, highlighting the importance of trial stimulation for long-term success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Spinal cord stimulation in chronic neuropathic pain]. Meyerson, B., Linderoth, B., Lind, G.[2016]

In a study of 402 patients with chronic pain who received spinal cord stimulation (SCS) devices, 55% of those with lower limb pain and 67% with upper limb pain reported a significant reduction in pain (≥50% reduction) after 2 years, indicating the long-term effectiveness of SCS.

The majority of patients (91%) were satisfied with their treatment, and 93% would choose to undergo the procedure again, while also showing a significant decrease in the need for pain medications, highlighting both the efficacy and safety of SCS therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spinal cord stimulation for chronic refractory pain: Long-term effectiveness and safety data from a multicentre registry. Brinzeu, A., Cuny, E., Fontaine, D., et al.[2019]

In a study of 68 patients who had spinal cord stimulation paddle electrodes removed, the most common reason for removal was loss of coverage or effect (75%), indicating that while SCS is effective, it may not always provide lasting relief.

Postoperative complications occurred in 11.75% of patients, with two major complications requiring reoperation, highlighting that while SCS removal is generally safe, it does carry some risks that patients should be aware of.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rate of Complications Following Spinal Cord Stimulation Paddle Electrode Removal. Maldonado-Naranjo, AL., Frizon, LA., Sabharwal, NC., et al.[2022]

In a study of 19 patients using spinal cord stimulation (SCS) for chronic pain, 74% preferred stimulation settings that produced sensations (above sensory threshold) over those that did not (below threshold), indicating a strong preference for the former in improving quality of life.

Patients using above threshold stimulation showed significant improvements in depression scores after three months, although they reported worse sleepiness, suggesting that while effective for pain management, this setting may impact sleep quality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective Evaluation of Patient Usage of Above and Below Threshold Waveforms With Traditional Spinal Cord Stimulation Devices. Owusu, S., Huynh, A., Gruenthal, E., et al.[2022]

In a study of 8326 patients who underwent spinal cord stimulation (SCS) implantation, the overall incidence of spinal cord injury (SCI) was found to be low at 2.13%, indicating that SCS is a generally safe procedure.

There was no significant difference in the rates of SCI or spinal hematoma between patients receiving percutaneous (2.35%) and paddle (1.71%) electrode implantation, suggesting similar safety profiles for both methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Incidence of Spinal Cord Injury in Implantation of Percutaneous and Paddle Electrodes for Spinal Cord Stimulation. Petraglia, FW., Farber, SH., Gramer, R., et al.[2022]

In a study of 48 chronic pain patients using tonic spinal cord stimulation (SCS), it was found that SCS reduced touch sensitivity in the area of the body where stimulation was applied, indicating some effect on sensory perception.

However, the overall impact of SCS on sensory perception was minimal, and the changes observed were not deemed clinically significant, suggesting that SCS may not substantially alter patients' daily experiences of pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Tonic Spinal Cord Stimulation on External Mechanical and Thermal Stimuli Perception Using Quantitative Sensory Testing: A Multicenter Stimulation ON-OFF Study on Chronic Pain Patients. Bordeleau, M., Carrondo Cottin, S., Cantin, L., et al.[2021]

In a study involving patients undergoing spinal cord stimulation (SCS) trials, the Observational Mechanical Gateway (OMG) Connector provided an additional option for stimulation, leading to an overall pain score reduction from 7.3 to 2.6 on a 10-point scale, indicating effective pain management.

Despite the small sample size, 12 out of 16 participants chose to proceed with permanent implantation after the trial, suggesting that the OMG Connector may enhance patient satisfaction and treatment access during SCS trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of observational mechanical gateway connector in spinal cord stimulation trials. Kim, CH., Issa, MA., Vaglienti, RM.[2011]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Experience with spinal cord stimulation (SCS) in the management of chronic pain in a traumatic transverse lesion syndrome. [2019]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Transcutaneous Electrical Spinal Cord Stimulation to Promote Recovery in Chronic Spinal Cord Injury. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Transcutaneous spinal cord stimulation and motor responses in individuals with spinal cord injury: A methodological review. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Optimizing sensory fiber activation during cervical transcutaneous spinal stimulation using different electrode configurations: A computational analysis. [2022]

5. Sweden pubmed.ncbi.nlm.nih.gov

[Spinal cord stimulation in chronic neuropathic pain]. [2016]

6. England pubmed.ncbi.nlm.nih.gov

Spinal cord stimulation for chronic refractory pain: Long-term effectiveness and safety data from a multicentre registry. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Rate of Complications Following Spinal Cord Stimulation Paddle Electrode Removal. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Prospective Evaluation of Patient Usage of Above and Below Threshold Waveforms With Traditional Spinal Cord Stimulation Devices. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

The Incidence of Spinal Cord Injury in Implantation of Percutaneous and Paddle Electrodes for Spinal Cord Stimulation. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Effects of Tonic Spinal Cord Stimulation on External Mechanical and Thermal Stimuli Perception Using Quantitative Sensory Testing: A Multicenter Stimulation ON-OFF Study on Chronic Pain Patients. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

Use of observational mechanical gateway connector in spinal cord stimulation trials. [2011]