Spinal Root and Spinal Cord Stimulation for Restoration of Function in Lower-Limb Amputees (SCS-LL)

The goals of this study are to provide sensory information to amputees and reduce phantom limb pain via electrical stimulation of the lumbar spinal cord and spinal nerves. The spinal nerves convey sensory information from peripheral nerves to higher order centers in the brain. These structures still remain intact after amputation and electrical stimulation of the dorsal spinal nerves in individuals with intact limbs and amputees has been demonstrated to generate paresthetic sensory percepts referred to portions of the distal limb. Further, there is recent evidence that careful modulation of stimulation parameters can convert paresthetic sensations to more naturalistic ones when stimulating peripheral nerves in amputees. However, it is currently unclear whether it is possible to achieve this same conversion when stimulating the spinal nerves, and if those naturalistic sensations can have positive effects on phantom limb pain. As a first step towards those goals, in this study, the investigators will quantify the sensations generated by electrical stimulation of the spinal nerves, study the relationship between stimulation parameters and the quality of those sensations, measure changes in control of a prosthesis with sensory stimulation, and quantify the effects of that stimulation on the perception of the phantom limb and any associated pain.

Study Overview

• Status: Completed
• Conditions: Phantom Limb Pain; Traumatic Amputation of Lower Extremity
• Intervention / Treatment: Device: Spinal cord stimulator

Detailed Description

During the study, FDA-cleared spinal cord stimulator leads will be placed in the lumbar epidural space of lower limb amputees and steered laterally towards the dorsal spinal roots under fluoroscopic guidance. This approach is essentially identical to the FDA-cleared procedure in which these devices are placed in the lumbar epidural space for treatment of intractable low back and leg pain. In that procedure, it is common clinical practice to place 2-3 leads temporarily in the epidural space through a percutaneous approach and perform a multiday trial to determine if the patient experiences any pain reduction from spinal cord stimulation. Following the trial, the percutaneous leads are typically removed by gently pulling on them, and the patient is referred to a neurosurgeon for permanent surgical implantation.

Similarly, in this study, the device will be tunneled percutaneously through the skin and secured in place with tape or suture. Using the stylet included with the spinal cord stimulator leads, the devices will be steered laterally under fluoroscopic guidance to target the dorsal spinal nerves. During lab experiments, the leads will be connected to an external stimulator. In this study, the devices will remain in the epidural space for less than 30 days and will be removed by gently pulling on the external portion. Throughout the study, the investigators will perform a series of psychophysical evaluations to characterize the sensory percepts evoked by epidural stimulation, along with functional evaluations of the effects of stimulation on the ability to control a prosthetic limb. In addition, the investigators will perform surveys to characterize changes in phantom limb sensation and pain that occur during stimulation.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15101
      • Debbie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• have an amputation of at least one lower limb, at a level between the ankle and hip joints
• be at least 6 months post-amputation at time of lead placement

Exclusion Criteria:

• women who are pregnant or breast-feeding
• has any serious diseases or disorders that affect ability to participate
• currently receiving medications that may affect blood coagulation
• allergic to contrast medium, or has kidney failure that could be exacerbated by contrast agent
• implanted metallic devices that are not cleared for MRI

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Spinal cord stimulation; Spinal cord stimulator leads (2-3 leads) will be placed in the lumbar epidural space of lower limb amputees to determine if the patient experiences any pain reduction from spinal cord stimulation. Participants in this study receive spinal cord stimulation will be trans-tibial and trans-femoral amputees that are at least six month post--amputation. Subjects will have varying levels of phantom limb sensation and pain, but should have no other significant neurological disorders.

Device: Spinal cord stimulator; Spinal cord stimulator leads (2-3 leads) will be placed in the lumbar epidural space of lower limb amputees to determine if the patient experiences any pain reduction from spinal cord stimulation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stimulation perceptual thresholds to a variety of stimulus parameters	Quantify the threshold (minimum charge and pulse rate) stimulus required to evoke sensory percepts during epidural spinal nerve stimulation.	30 days
Stimulation neurophysiology thresholds to a variety of stimulus parameters	Quantify the threshold (minimum charge and pulse rate) stimulus required to evoke neurophysiological responses during epidural spinal nerve stimulation	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Location of evoked sensory percepts	Document where on the body the subject perceives the stimulation locations.	30 days
Qualitative self-report of evoked sensations	Document the subjective perception of lumbosacral epidural spinal nerve stimulation for restoration of sensation. The investigators will ask each subject to provide subjective feedback on their perceived utility of the sensory feedback provided by the device.	30 days
Change (reduction) in pain ratings	Document changes in phantom limb pain during and shortly after lumbosacral epidural spinal nerve stimulation in amputees. Before placement of the spinal cord stimulator leads, investigators will document the subject's description of their history of perceived phantom limb. Investigators will ask them to periodically update their perception of the limb throughout each experimental session, as well as within a month after the device has been removed.	30 days
Ability to use a prosthetic limb with neural signals	Investigators will test the subject's success rate during control of prosthetic limb with and without sensory feedback provided by electrical stimulation of the spinal roots. Using either a virtual prosthetic limb or an instrumented prosthesis, stimulation of the spinal roots will be modulated based on signals recorded from the limb.	30 days

Collaborators and Investigators

• Sponsor: University of Pittsburgh
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)

Publications and helpful links

General Publications

• Ziegler-Graham K, MacKenzie EJ, Ephraim PL, Travison TG, Brookmeyer R. Estimating the prevalence of limb loss in the United States: 2005 to 2050. Arch Phys Med Rehabil. 2008 Mar;89(3):422-9. doi: 10.1016/j.apmr.2007.11.005.
• Raichle KA, Hanley MA, Molton I, Kadel NJ, Campbell K, Phelps E, Ehde D, Smith DG. Prosthesis use in persons with lower- and upper-limb amputation. J Rehabil Res Dev. 2008;45(7):961-72. doi: 10.1682/jrrd.2007.09.0151.
• Etter K, Borgia M, Resnik L. Prescription and repair rates of prosthetic limbs in the VA healthcare system: implications for national prosthetic parity. Disabil Rehabil Assist Technol. 2015 Nov;10(6):493-500. doi: 10.3109/17483107.2014.921246. Epub 2014 May 22.
• Deer TR, Grigsby E, Weiner RL, Wilcosky B, Kramer JM. A prospective study of dorsal root ganglion stimulation for the relief of chronic pain. Neuromodulation. 2013 Jan-Feb;16(1):67-71; discussion 71-2. doi: 10.1111/ner.12013. Epub 2012 Dec 14.
• Liem L, Russo M, Huygen FJ, Van Buyten JP, Smet I, Verrills P, Cousins M, Brooker C, Levy R, Deer T, Kramer J. A multicenter, prospective trial to assess the safety and performance of the spinal modulation dorsal root ganglion neurostimulator system in the treatment of chronic pain. Neuromodulation. 2013 Sep-Oct;16(5):471-82; discussion 482. doi: 10.1111/ner.12072. Epub 2013 May 13.

Study record dates

Study Major Dates

• Study Start (Actual): March 16, 2017
• Primary Completion (Actual): March 4, 2021
• Study Completion (Actual): September 8, 2021

Study Registration Dates

• First Submitted: October 5, 2016
• First Submitted That Met QC Criteria: January 18, 2017
• First Posted (Estimate): January 23, 2017

Study Record Updates

• Last Update Posted (Actual): April 12, 2022
• Last Update Submitted That Met QC Criteria: April 11, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Pain; Phantom Limb Pain; Stimulation; Lower-Limb Amputation; Sensation; Electrodes
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Postoperative Complications; Pain; Neurologic Manifestations; Wounds and Injuries; Neurobehavioral Manifestations; Perceptual Disorders; Pain, Postoperative; Amputation, Traumatic; Phantom Limb
• Other Study ID Numbers: STUDY19030223; UH3NS100541 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The research team may share de-identified data with scientists at other centers for the purpose of data analysis and collaboration. Research information and data may be shared with investigators conducting other research.
• IPD Sharing Time Frame: Information may be shared while data is being recorded, analyzed, and/or prior to publication. Data may be available after manuscripts are published.
• IPD Sharing Access Criteria: Data may be shared through a restricted access portal created by the National Institutes of Health or directly with scientists at other centers under a data use agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No