<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03027947</url>
  </required_header>
  <id_info>
    <org_study_id>STUDY19030223</org_study_id>
    <secondary_id>UH3NS100541</secondary_id>
    <nct_id>NCT03027947</nct_id>
  </id_info>
  <brief_title>Spinal Root and Spinal Cord Stimulation for Restoration of Function in Lower-Limb Amputees</brief_title>
  <acronym>SCS-LL</acronym>
  <official_title>Spinal Root and Spinal Cord Stimulation for Restoration of Function in Lower-Limb Amputees</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Pittsburgh</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Neurological Disorders and Stroke (NINDS)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Pittsburgh</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The goals of this study are to provide sensory information to amputees and reduce phantom&#xD;
      limb pain via electrical stimulation of the lumbar spinal cord and spinal nerves. The spinal&#xD;
      nerves convey sensory information from peripheral nerves to higher order centers in the&#xD;
      brain. These structures still remain intact after amputation and electrical stimulation of&#xD;
      the dorsal spinal nerves in individuals with intact limbs and amputees has been demonstrated&#xD;
      to generate paresthetic sensory percepts referred to portions of the distal limb. Further,&#xD;
      there is recent evidence that careful modulation of stimulation parameters can convert&#xD;
      paresthetic sensations to more naturalistic ones when stimulating peripheral nerves in&#xD;
      amputees. However, it is currently unclear whether it is possible to achieve this same&#xD;
      conversion when stimulating the spinal nerves, and if those naturalistic sensations can have&#xD;
      positive effects on phantom limb pain. As a first step towards those goals, in this study,&#xD;
      the investigators will quantify the sensations generated by electrical stimulation of the&#xD;
      spinal nerves, study the relationship between stimulation parameters and the quality of those&#xD;
      sensations, measure changes in control of a prosthesis with sensory stimulation, and quantify&#xD;
      the effects of that stimulation on the perception of the phantom limb and any associated&#xD;
      pain.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      During the study, FDA-cleared spinal cord stimulator leads will be placed in the lumbar&#xD;
      epidural space of lower limb amputees and steered laterally towards the dorsal spinal roots&#xD;
      under fluoroscopic guidance. This approach is essentially identical to the FDA-cleared&#xD;
      procedure in which these devices are placed in the lumbar epidural space for treatment of&#xD;
      intractable low back and leg pain. In that procedure, it is common clinical practice to place&#xD;
      2-3 leads temporarily in the epidural space through a percutaneous approach and perform a&#xD;
      multiday trial to determine if the patient experiences any pain reduction from spinal cord&#xD;
      stimulation. Following the trial, the percutaneous leads are typically removed by gently&#xD;
      pulling on them, and the patient is referred to a neurosurgeon for permanent surgical&#xD;
      implantation.&#xD;
&#xD;
      Similarly, in this study, the device will be tunneled percutaneously through the skin and&#xD;
      secured in place with tape or suture. Using the stylet included with the spinal cord&#xD;
      stimulator leads, the devices will be steered laterally under fluoroscopic guidance to target&#xD;
      the dorsal spinal nerves. During lab experiments, the leads will be connected to an external&#xD;
      stimulator. In this study, the devices will remain in the epidural space for less than 30&#xD;
      days and will be removed by gently pulling on the external portion. Throughout the study, the&#xD;
      investigators will perform a series of psychophysical evaluations to characterize the sensory&#xD;
      percepts evoked by epidural stimulation, along with functional evaluations of the effects of&#xD;
      stimulation on the ability to control a prosthetic limb. In addition, the investigators will&#xD;
      perform surveys to characterize changes in phantom limb sensation and pain that occur during&#xD;
      stimulation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 16, 2017</start_date>
  <completion_date type="Actual">September 8, 2021</completion_date>
  <primary_completion_date type="Actual">March 4, 2021</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Stimulation perceptual thresholds to a variety of stimulus parameters</measure>
    <time_frame>30 days</time_frame>
    <description>Quantify the threshold (minimum charge and pulse rate) stimulus required to evoke sensory percepts during epidural spinal nerve stimulation.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Stimulation neurophysiology thresholds to a variety of stimulus parameters</measure>
    <time_frame>30 days</time_frame>
    <description>Quantify the threshold (minimum charge and pulse rate) stimulus required to evoke neurophysiological responses during epidural spinal nerve stimulation</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Location of evoked sensory percepts</measure>
    <time_frame>30 days</time_frame>
    <description>Document where on the body the subject perceives the stimulation locations.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Qualitative self-report of evoked sensations</measure>
    <time_frame>30 days</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change (reduction) in pain ratings</measure>
    <time_frame>30 days</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ability to use a prosthetic limb with neural signals</measure>
    <time_frame>30 days</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">5</enrollment>
  <condition>Traumatic Amputation of Lower Extremity</condition>
  <condition>Phantom Limb Pain</condition>
  <arm_group>
    <arm_group_label>Spinal cord stimulation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.&#xD;
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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Spinal cord stimulator</intervention_name>
    <description>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.</description>
    <arm_group_label>Spinal cord stimulation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  have an amputation of at least one lower limb, at a level between the ankle and hip&#xD;
             joints&#xD;
&#xD;
          -  be at least 6 months post-amputation at time of lead placement&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  women who are pregnant or breast-feeding&#xD;
&#xD;
          -  has any serious diseases or disorders that affect ability to participate&#xD;
&#xD;
          -  currently receiving medications that may affect blood coagulation&#xD;
&#xD;
          -  allergic to contrast medium, or has kidney failure that could be exacerbated by&#xD;
             contrast agent&#xD;
&#xD;
          -  implanted metallic devices that are not cleared for MRI&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lee Fisher, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pittsburgh</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Debbie</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15101</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>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.</citation>
    <PMID>18295618</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>24852068</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>19165686</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>23240657</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>23668228</PMID>
  </reference>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>October 5, 2016</study_first_submitted>
  <study_first_submitted_qc>January 18, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 23, 2017</study_first_posted>
  <last_update_submitted>April 11, 2022</last_update_submitted>
  <last_update_submitted_qc>April 11, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 12, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Pittsburgh</investigator_affiliation>
    <investigator_full_name>Lee Fisher, PhD</investigator_full_name>
    <investigator_title>Assistant Professor, School of Medicine, Physical Medicine and Rehabilitation</investigator_title>
  </responsible_party>
  <keyword>Phantom Limb Pain</keyword>
  <keyword>Lower-Limb Amputation</keyword>
  <keyword>Electrodes</keyword>
  <keyword>Stimulation</keyword>
  <keyword>Pain</keyword>
  <keyword>Sensation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Phantom Limb</mesh_term>
    <mesh_term>Amputation, Traumatic</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_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_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_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_time_frame>
    <ipd_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_access_criteria>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03027947
org study id: STUDY19030223
secondary id: UH3NS100541
nct id: NCT03027947
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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.
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.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Stimulation perceptual thresholds to a variety of stimulus parameters
time frame: 30 days
description: Quantify the threshold (minimum charge and pulse rate) stimulus required to evoke sensory percepts during epidural spinal nerve stimulation.
measure: Stimulation neurophysiology thresholds to a variety of stimulus parameters
time frame: 30 days
description: Quantify the threshold (minimum charge and pulse rate) stimulus required to evoke neurophysiological responses during epidural spinal nerve stimulation
measure: Location of evoked sensory percepts
time frame: 30 days
description: Document where on the body the subject perceives the stimulation locations.
measure: Qualitative self-report of evoked sensations
time frame: 30 days
description: 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.
measure: Change (reduction) in pain ratings
time frame: 30 days
description: 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.
measure: Ability to use a prosthetic limb with neural signals
time frame: 30 days
description: 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.
arm group label: Spinal cord stimulation
arm group type: Experimental
description: 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.
intervention type: Device
intervention name: Spinal cord stimulator
description: 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.
arm group label: Spinal cord stimulation
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Lee Fisher, PhD
role: Principal Investigator
affiliation: University of Pittsburgh
facility: 
country: United States
citation: 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.
PMID: 18295618
citation: 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.
PMID: 24852068
citation: 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.
PMID: 19165686
citation: 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.
PMID: 23240657
citation: 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.
PMID: 23668228
responsible party type: Principal Investigator
investigator affiliation: University of Pittsburgh
investigator full name: Lee Fisher, PhD
investigator title: Assistant Professor, School of Medicine, Physical Medicine and Rehabilitation
mesh term: Phantom Limb
mesh term: Amputation, Traumatic
sharing ipd: Yes
ipd 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 info type: Study Protocol
ipd info type: Informed Consent Form (ICF)
ipd 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 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.