Neuromodulation in Lower Limb Amputees

Overview

The goal of this study is to investigate the role of transcutaneous spinal cord stimulation on spinal cord excitability in lower limb amputees. In this study, the investigators will quantify the spinal cord excitability determined by 1) reflexes and electromyography, and 2) phantom limb pain using self-reported pain assessments. The investigators will assess these measures of spinal excitability in lower limb amputees before and after transcutaneous spinal cord stimulation.

Full Title of Study: “Spinal Excitability Changes and Transcutaneous Spinal Cord Stimulation in Lower Limb Amputees”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Basic Science
    • Masking: None (Open Label)
  • Study Primary Completion Date: June 29, 2022

Detailed Description

The overall goal of this work is to investigate the changes in the spinal cord resulting from limb amputation. Limb amputation results in an extreme form of peripheral nerve injury. Damage to peripheral nerves, such as with neuropathy, crush injuries, nerve transection, or limb amputation often results in chronic pain, which may be associated with altered excitability of spinal sensorimotor pathways. These spinal pathways become hyperexcitable due to a lack of sensory input, which causes tonic disinhibition of descending circuits and spontaneous activity in the dorsal root ganglia (DRG). Spinal excitability can be measured using the H-reflex, in which electrical stimulation of muscle spindle Ia afferents activates spinal motoneurons via the myotatic reflex, as well as the posterior root-muscle (PRM) reflex, which is elicited by transcutaneous stimulation over the dorsal roots and is considered to be half of the H-reflex, excluding the peripheral primary afferents, but with multiple root activation. Spinal excitability has not been measured in amputees but may offer a potential biomarker for PLP. Neuromodulation may restore normal spinal excitability and reduce PLP, thus offering the potential to improve the quality of life in individuals with a lower limb amputation. The results of this study will provide the foundation for future development of a neuroprosthesis to restore spinal excitability and reduce PLP in individuals with a lower limb amputation. Subjects will undergo 5 testing and stimulation sessions in 1 week. An additional 3 days of recording sessions may be necessary if a phantom limb pain episode does not occur during normal testing days. Specific Aim 1: Quantify spinal excitability. A lack of sensory input results in spinal hyperexcitability through several pathways including tonic disinhibition of descending circuits and spontaneous activity in the DRG. Spinal cord excitability is directly related to reflex modulation; impaired or enhanced reflex modulation indicates abnormal spinal cord excitability. Spinal cord excitability will be determined in people with a lower limb amputation using the H-reflex and posterior root-muscle (PRM) reflex. The H-reflex is elicited with electrical stimulation of peripheral nerves, exciting muscle spindle Ia afferents projecting to spinal motoneurons via the myotatic reflex. Stimulation of the peripheral nerves also elicits a direct motor (M) wave. The PRM reflex is elicited by electrical stimulation of the posterior roots on the back. It is considered to be half of the H-reflex, excluding the peripheral motor efferents, but activates multiple dorsal roots. Reflex amplitude and latency, threshold, recruitment curves, and rate-dependent depression will be measured and compared to intact controls. The investigators hypothesize that H and PRM reflex hyperexcitability will be present in the residual limb of amputees with PLP. These results will provide insight into the role of limb amputation on spinal cord health and excitability. Specific Aim 2: Characterize the effects of transcutaneous spinal cord stimulation on spinal cord excitability and phantom limb pain. Neuromodulation of sensorimotor pathways using transcutaneous electrical nerve stimulation (TENS), dorsal root ganglia stimulation (DRGS), and epidural spinal cord stimulation (eSCS) to reduce phantom limb pain have been explored with mixed results. The most promising methods for pain reduction were DRGS or laterally-placed eSCS, indicating that the DRG and dorsal roots are optimal targets for reducing PLP. However, these methods require surgical implantation of electrodes. Transcutaneous spinal cord stimulation (tSCS) is a non-invasive method for stimulating the dorsal roots in a similar way as eSCS. Through activation of the primary afferents, tSCS may inhibit pain pathways and reduce the hyperexcitability that leads to chronic pain. tSCS in people with spinal cord injury has been shown to restore spinal inhibition and reduce H-reflex hyperexcitability. The investigators hypothesize that tSCS can reduce PLP through modulation of sensorimotor pathways. By comparing the H- and PRM reflex excitability recorded from the residual limb before and after each session of tSCS, a potential mechanism of PLP could be elucidated. H- and PRM reflex modulation, and any differences in the extent of modulation for each, can further inform on the mechanisms of tSCS and how it modulates sensorimotor pathways. The investigators will also quantify the subjects' experience of PLP before and after the 5 days of tSCS and correlate their pain experiences with spinal excitability measures. The investigators will use a visual analog scale and the McGill Pain Questionnaire to assess changes in pain perception. The investigators will also use an algometer to determine changes in local pain threshold.

Interventions

  • Device: Transcutaneous spinal cord stimulation
    • Neuromodulation with transcutaneous spinal cord stimulation applied on lower back adjacent to spine for 30-60 minutes for 5 consecutive days.

Arms, Groups and Cohorts

  • Experimental: Transcutaneous spinal cord stimulation
    • Transcutaneous spinal cord stimulation on lower back for 30-60 minutes for 5 consecutive days.

Clinical Trial Outcome Measures

Primary Measures

  • Mean H-reflex Threshold
    • Time Frame: Day 2
    • Reflex threshold: stimulation amplitude required to evoke reflex response. The presence of H-reflexes are expected in uninjured individuals.
  • Mean H-reflex Threshold
    • Time Frame: Day 3
    • Reflex threshold: stimulation amplitude required to evoke reflex response. The presence of H-reflexes are expected in uninjured individuals.
  • Mean H-reflex Threshold
    • Time Frame: Day 4
    • Reflex threshold: stimulation amplitude required to evoke reflex response. The presence of H-reflexes are expected in uninjured individuals.
  • Mean H-reflex Threshold
    • Time Frame: Day 5
    • Reflex threshold: stimulation amplitude required to evoke reflex response. The presence of H-reflexes are expected in uninjured individuals.
  • Mean PRM Reflex Threshold
    • Time Frame: Day 2
    • Reflex threshold: stimulation amplitude required to evoke reflex response. Thresholds in uninjured people have been reported to be approximately 30 mA.
  • Mean PRM Reflex Threshold
    • Time Frame: Day 3
    • Reflex threshold: stimulation amplitude required to evoke reflex response. Thresholds in uninjured people have been reported to be approximately 30 mA.
  • Mean PRM Reflex Threshold
    • Time Frame: Day 4
    • Reflex threshold: stimulation amplitude required to evoke reflex response. Thresholds in uninjured people have been reported to be approximately 30 mA.
  • Mean PRM Reflex Threshold
    • Time Frame: Day 5
    • Reflex threshold: stimulation amplitude required to evoke reflex response. Thresholds in uninjured people have been reported to be approximately 30 mA.

Secondary Measures

  • Phantom Limb Pain Score
    • Time Frame: Day 5
    • McGill Pain Questionnaire: minimum = 0, maximum = 78, the higher the pain score the greater the pain
  • Pain Pressure Threshold
    • Time Frame: Day 5
    • Pain Pressure Threshold Test using an algometer: minimum force that induces pain, minimum = 0 N, maximum = 444.8 N, a lower threshold indicates hypersensitivity
  • Pain Score
    • Time Frame: Day 2
    • Visual analog scale: minimum = 0, maximum = 10, the higher the score the greater the pain
  • Pain Score
    • Time Frame: Day 3
    • Visual analog scale: minimum = 0, maximum = 10, the higher the score the greater the pain
  • Pain Score
    • Time Frame: Day 4
    • Visual analog scale: minimum = 0, maximum = 10, the higher the score the greater the pain
  • Pain Score
    • Time Frame: Day 5
    • Visual analog scale: minimum = 0, maximum = 10, the higher the score the greater the pain

Participating in This Clinical Trial

Inclusion Criteria

  • Participants must be between the ages of 21 and 70 years old. – Participants must have a trans-tibial amputation and phantom limb pain in at least one leg Exclusion Criteria:

  • Participants must not have any serious disease, disorder, or infection (ex. blood or bone disorder or infection) that could affect their ability to participate in this study. – Female participants of child-bearing potential must not be pregnant or breast feeding, or plan to become pregnant during the course of the study. – Participants must not have any implanted stimulators or pulse generators – Participants must not have any implanted metallic devices in their torso and/or legs – Participants must not have heart disease, including known arrhythmia

Gender Eligibility: All

Minimum Age: 21 Years

Maximum Age: 70 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • University of Pittsburgh
  • Collaborator
    • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  • Provider of Information About this Clinical Study
    • Principal Investigator: Lee Fisher, PhD, PhD, Assistant Professor – University of Pittsburgh
  • Overall Official(s)
    • Lee Fisher, PhD, Principal Investigator, University of Pittsburgh

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.