Neuromodulation in Lower Limb Amputees

Amputation Clinical Trial

Official title:

Spinal Excitability Changes and Transcutaneous Spinal Cord Stimulation in Lower Limb Amputees

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04543786
• Other study ID #: STUDY20060101
• Secondary ID: P2CHD086844
• Status: Terminated
• Phase: N/A
• Start date: March 7, 2022
• Est. completion date: June 29, 2022

Study information

• Verified date: June 2023
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: June 29, 2022
• Est. primary completion date: June 29, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Amputation
• Hoffman's Reflex
• Phantom Limb
• Phantom Limb Pain
• Reflex, Abnormal

Intervention

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.

Locations

Country	Name	City	State
United States	Carnegie Mellon University	Pittsburgh	Pennsylvania
United States	University of Pittsburgh	Pittsburgh	Pennsylvania

Sponsors (4)

Lead Sponsor	Collaborator
University of Pittsburgh	Carnegie Mellon University, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Medical University of South Carolina

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean H-reflex Threshold	Reflex threshold: stimulation amplitude required to evoke reflex response. The presence of H-reflexes are expected in uninjured individuals.	Day 2
Primary	Mean H-reflex Threshold	Reflex threshold: stimulation amplitude required to evoke reflex response. The presence of H-reflexes are expected in uninjured individuals.	Day 3
Primary	Mean H-reflex Threshold	Reflex threshold: stimulation amplitude required to evoke reflex response. The presence of H-reflexes are expected in uninjured individuals.	Day 4
Primary	Mean H-reflex Threshold	Reflex threshold: stimulation amplitude required to evoke reflex response. The presence of H-reflexes are expected in uninjured individuals.	Day 5
Primary	Mean PRM Reflex Threshold	Reflex threshold: stimulation amplitude required to evoke reflex response. Thresholds in uninjured people have been reported to be approximately 30 mA.	Day 2
Primary	Mean PRM Reflex Threshold	Reflex threshold: stimulation amplitude required to evoke reflex response. Thresholds in uninjured people have been reported to be approximately 30 mA.	Day 3
Primary	Mean PRM Reflex Threshold	Reflex threshold: stimulation amplitude required to evoke reflex response. Thresholds in uninjured people have been reported to be approximately 30 mA.	Day 4
Primary	Mean PRM Reflex Threshold	Reflex threshold: stimulation amplitude required to evoke reflex response. Thresholds in uninjured people have been reported to be approximately 30 mA.	Day 5
Secondary	Phantom Limb Pain Score	McGill Pain Questionnaire: minimum = 0, maximum = 78, the higher the pain score the greater the pain	Day 5
Secondary	Pain Pressure Threshold	Pain Pressure Threshold Test using an algometer: minimum force that induces pain, minimum = 0 N, maximum = 444.8 N, a lower threshold indicates hypersensitivity	Day 5
Secondary	Pain Score	Visual analog scale: minimum = 0, maximum = 10, the higher the score the greater the pain	Day 2
Secondary	Pain Score	Visual analog scale: minimum = 0, maximum = 10, the higher the score the greater the pain	Day 3
Secondary	Pain Score	Visual analog scale: minimum = 0, maximum = 10, the higher the score the greater the pain	Day 4
Secondary	Pain Score	Visual analog scale: minimum = 0, maximum = 10, the higher the score the greater the pain	Day 5