Neuromodulation for Chronic Pain

Overseen By Fady Girgis, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Alberta Health Services, Calgary

Disqualifiers: Non-English speaking

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: Unknown

Duration: 6 months

20 Participants Needed

Trial Summary

Do I need to stop taking my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment for chronic pain?

Research shows that electrical stimulation, a key part of neuromodulation, can help manage chronic pain by activating the body's pain modulation network. While it may not provide significant relief for all patients, it has been effective in some cases, and combining it with other therapies might improve outcomes. ^{1 2 3 4 5}

Is neuromodulation for chronic pain generally safe for humans?

Research indicates that a wide range of stimulation parameters used in neuromodulation are considered safe, and studies have shown that these treatments can be safely incorporated into standard practice. However, it is important for devices to be properly calibrated and for practitioners to be trained to ensure safe use. ^{6 7 8 9 10}

How is the treatment of chronic pain with neuromodulation different from other treatments?

Neuromodulation for chronic pain is unique because it uses electrical stimulation to modulate the nervous system, offering a non-destructive and reversible approach that can be adjusted over time. Unlike traditional methods that may involve surgery or medication, this treatment can be tailored to the patient's evolving condition, providing a more resilient and adaptable solution. ^{2 4 5 11 12}

What is the purpose of this trial?

The objective of this study is to determine the efficacy of neuromodulation using various stimulation paradigms in the treatment of several disorders including chronic pain.

Eligibility Criteria

This trial is for individuals who experience chronic pain and are candidates for a neuromodulation device implant, which they have agreed to receive. Participants must be able to communicate in English.

Inclusion Criteria

You are planning to have a neuromodulation device implanted and have already agreed to it.

Exclusion Criteria

Non-English speaking

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive neuromodulation treatment using various stimulation paradigms in a blinded fashion

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Stimulation parameters

Trial Overview The study aims to test the effectiveness of different stimulation settings on a neuromodulation device that's implanted in patients with chronic pain conditions.

Participant Groups

Group I: Industry standard stimulation Active Control 1 Intervention

Industry standard stimulation settings

Group II: Experimental stimulation Placebo Group 1 Intervention

Experimental stimulation settings

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

Approved in United States as Electrical Stimulation Therapy for:

• Chronic Pain Management
• Muscle Rehabilitation
• Neurological Disorders

Approved in European Union as Neuromodulation Therapy for:

• Chronic Pain Relief
• Muscle Stimulation
• Neurological Rehabilitation

Approved in Canada as Stimulation Therapy for:

• Pain Management
• Muscle Recovery
• Neurological Conditions

Who Is Running the Clinical Trial?

Alberta Health Services, Calgary

Lead Sponsor

Trials

15

Recruited

2,600+

Findings from Research

The study evaluated the effects of different electrical stimulation techniques on pain relief using the nociceptive RIII reflex in 24 healthy volunteers, revealing that non-noxious TENS provided temporary relief, while noxious TENS produced both immediate facilitation and significant inhibitory after-effects.

The piezo-electric current (PECs1) demonstrated powerful and long-lasting pain relief effects, particularly when applied to areas away from the pain site, suggesting its potential as a clinically effective treatment for pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Depressive effects of segmental and heterotopic application of transcutaneous electrical nerve stimulation and piezo-electric current on lower limb nociceptive flexion reflex in human subjects. Danziger, N., Rozenberg, S., Bourgeois, P., et al.[2019]

Electrical stimulation of the motor cortex using different electrode polarities (anode, cathode, or bipole) significantly affects how neural elements respond, with anodal stimulation favoring perpendicular excitation and cathodal stimulation favoring parallel excitation.

The study's modeling approach reveals that the position and polarity of electrodes can optimize chronic pain management therapies by influencing the excitation thresholds of cortical neurons, potentially leading to more effective treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anodal vs cathodal stimulation of motor cortex: a modeling study. Manola, L., Holsheimer, J., Veltink, P., et al.[2023]

External electrical stimulation effectively controls acute pain in approximately 80% of patients, making it a promising option for immediate pain relief.

For chronic pain, however, only about 25% of patients experience significant relief from this method, suggesting the need for a more comprehensive treatment approach that includes therapies like operant conditioning and physical exercise.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The viability of external electrical stimulation as a therapeutic modality. Shealy, CN.[2011]

In a pilot study involving 31 participants with chronic intractable pain, a novel neurostimulation waveform (anatomical pulsed stimulation, aPSP) significantly reduced pain more effectively than traditional spinal cord stimulation (T-SCS), with a 60% reduction in back pain and 63% in leg pain compared to 46% and 43% respectively for T-SCS.

The aPSP approach not only showed higher responder rates (61% for back pain and 78% for leg pain) but also suggests a multimechanistic action by targeting specific neural pathways, indicating its potential as an effective treatment for chronic pain, although further studies are needed to validate these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Novel Pulsed Stimulation Pattern in Spinal Cord Stimulation: Clinical Results and Postulated Mechanisms of Action in the Treatment of Chronic Low Back and Leg Pain. Desai, MJ., Salmon, J., Verrills, P., et al.[2023]

Recent advancements in understanding how pain is transmitted and modulated have led to new surgical options for managing chronic pain, particularly for cases that do not respond to traditional treatments.

Neurostimulation techniques, such as spinal cord stimulation and deep brain stimulation, can effectively activate the body's pain modulation network, offering a promising approach for treating chronic pain that is difficult to control with medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuromodulation techniques for medically refractory chronic pain. Landau, B., Levy, RM.[2022]

A large prospective study on spinal stimulating electrodes revealed that the technical grade of a stimulator is directly related to its range of stimulation for pain treatment.

The study statistically compared various stimulus parameters, including phase, polarity, and orientation of bipolar electrodes, indicating that these factors significantly influence the effectiveness of pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spinal stimulation: statistical superiority of monophasic stimulation of narrowly separated, longitudinal bipoles having rostral cathodes. Law, JD.[2019]

This manuscript introduces a new electrical definition of therapeutic dose for spinal cord stimulation (SCS) aimed at treating chronic pain, which is essential for establishing reliable dose-response relationships in neuromodulation therapies.

The proposed definition enhances the understanding of SCS's mechanism of action and suggests methods for personalizing and standardizing treatment doses, potentially improving the acceptance of SCS compared to traditional pharmacological treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Measures of Dosage for Spinal-Cord Electrical Stimulation: Review and Proposal. Single, PS., Scott, JB., Mugan, D.[2023]

The evaluation of three electrostimulators revealed that at least two measured parameters for each device were not within 25% of the manufacturer's claimed values, indicating a need for calibration to ensure accurate output.

While some pulse voltages exceeded safety standards for long-term use, short-term clinical use may still be safe; however, practitioners must be trained to use these devices properly to avoid potential tissue damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electrostimulators for acupuncture: safety issues. Lytle, CD., Thomas, BM., Gordon, EA., et al.[2004]

The Vectors study demonstrated that a standardized approach to spinal cord stimulation (SCS) using 1 kHz stimulation significantly reduced overall pain by an average of 45.4 mm on the visual analogue scale (VAS) at three months, with sustained results through 12 months.

At the 12-month mark, 79% of participants experienced at least a 50% improvement in pain, and 85% reported satisfaction with the therapy, indicating that this method not only alleviates pain but also enhances quality of life and functional outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Efficacy of a Novel Spinal Cord Stimulation Clinical Workflow Using Kilohertz Stimulation: Twelve-Month Results From the Vectors Study. Hatheway, JA., Mangal, V., Fishman, MA., et al.[2023]

The study identified 13 product codes for 8 types of neuromodulation devices, revealing a wealth of preclinical safety data from various animal models, which is crucial for understanding the effects of electrical neurostimulation.

Analysis of the data suggests that existing feline cortical models may not be suitable for evaluating tissue damage in peripheral nerve and spinal cord stimulation, highlighting the need for more relevant animal models in safety assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Public Regulatory Databases as a Source of Insight for Neuromodulation Devices Stimulation Parameters. Kumsa, D., Steinke, GK., Molnar, GF., et al.[2022]

Neurostimulation techniques, such as spinal cord stimulation and deep brain stimulation, offer a non-destructive and adjustable method for treating chronic pain, contrasting with older ablative techniques that often provided only temporary relief.

These modern neurostimulation approaches allow for tailored electrical current delivery, which can adapt to the dynamic nature of chronic pain conditions, potentially leading to more effective and long-lasting outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of chronic pain with neurostimulation. Birknes, JK., Sharan, A., Rezai, AR.[2019]

Chronic pain affects around 100 million adults in the US, and current neuropharmacology and neurostimulation therapies often have limited effectiveness and unclear mechanisms of action.

The study developed a simulation model that reveals how electrical neurostimulation interacts with sensory nerve activity, showing that higher stimulation frequencies can reduce the reliability of sensory signals, which may help improve our understanding of pain modulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electrical neurostimulation for chronic pain: On selective relay of sensory neural activities in myelinated nerve fibers. Sacré, P., Sarma, SV., Guan, Y., et al.[2020]

References

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

Depressive effects of segmental and heterotopic application of transcutaneous electrical nerve stimulation and piezo-electric current on lower limb nociceptive flexion reflex in human subjects. [2019]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Anodal vs cathodal stimulation of motor cortex: a modeling study. [2023]

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

The viability of external electrical stimulation as a therapeutic modality. [2011]

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

A Novel Pulsed Stimulation Pattern in Spinal Cord Stimulation: Clinical Results and Postulated Mechanisms of Action in the Treatment of Chronic Low Back and Leg Pain. [2023]

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

Neuromodulation techniques for medically refractory chronic pain. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Spinal stimulation: statistical superiority of monophasic stimulation of narrowly separated, longitudinal bipoles having rostral cathodes. [2019]

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

Measures of Dosage for Spinal-Cord Electrical Stimulation: Review and Proposal. [2023]

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

Electrostimulators for acupuncture: safety issues. [2004]

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

Long-Term Efficacy of a Novel Spinal Cord Stimulation Clinical Workflow Using Kilohertz Stimulation: Twelve-Month Results From the Vectors Study. [2023]

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

Public Regulatory Databases as a Source of Insight for Neuromodulation Devices Stimulation Parameters. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Treatment of chronic pain with neurostimulation. [2019]

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

Electrical neurostimulation for chronic pain: On selective relay of sensory neural activities in myelinated nerve fibers. [2020]