<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/NCT02205385</url>
  </required_header>
  <id_info>
    <org_study_id>TMR Neuroma</org_study_id>
    <secondary_id>OR120021</secondary_id>
    <nct_id>NCT02205385</nct_id>
  </id_info>
  <brief_title>Targeted Reinnervation as a Means to Treat Neuromas Associated With Major Limb Amputation</brief_title>
  <acronym>TMR</acronym>
  <official_title>Targeted Reinnervation as a Means to Treat Neuromas Associated With Major Limb Amputation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Northwestern University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>United States Department of Defense</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
  </sponsors>
  <source>Northwestern University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Subjects are being asked to participate in this study because they have an arm or leg&#xD;
      amputation and have developed pain related to a neuroma (an ongoing localized pain related to&#xD;
      a cut nerve ending).&#xD;
&#xD;
      We are studying two different types of surgery to treat the neuroma pain. Today there are&#xD;
      many surgical options reported which often means that there is no one best treatment. The&#xD;
      surgery that shows the best success so far, involves cutting out the scarred nerve ending&#xD;
      (neuroma) and burying the freshly cut nerve ending in a nearby muscle. Recently, a new&#xD;
      surgery has been developed called targeted reinnervation (TR). This surgery connects these&#xD;
      cut nerve endings to nerves going into nearby nonfunctional muscles. This surgery was&#xD;
      developed to allow amputees to have better prosthesis control. By chance, neuroma pain&#xD;
      improved significantly with TR. We, therefore, are conducting this clinical trial to evaluate&#xD;
      which of these two surgeries best treats neuroma pain. We will ask all participants to fill&#xD;
      out a questionnaire both before and after surgery. This will help us understand how a neuroma&#xD;
      affects the quality of life of amputees and will allow us to understand which surgery leads&#xD;
      to the best improvement in neuroma pain.&#xD;
&#xD;
      In order to confirm the presence and location of the neuroma before surgery, a magnetic&#xD;
      resonance image (MRI) will be performed. Taking these pictures requires subjects to lie still&#xD;
      for a short period of time but does not involve any invasive procedures. After surgery, the&#xD;
      MRI will be done again, this time to see if the nerve shows signs of scarring.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Loss of an arm or leg is a significant injury that affects a person's job prospects, personal&#xD;
      relationships, and overall quality of life. Approximately 25% of all amputees will develop&#xD;
      chronic local pain in the remaining part of their amputated limb. This pain is caused by&#xD;
      neuromas- disorganized nerve endings and scar tissue that form when an injured nerve tries to&#xD;
      heal. Every cut nerve will develop a neuroma unless the two ends of the nerve can be&#xD;
      rejoined. With limb amputation, the nerves are cut and one end is lost with the limb,&#xD;
      preventing the nerve from repairing itself. Instead, the cut nerve ending forms a painful&#xD;
      neuroma. Chronic pain from neuromas is a major reason that amputees cannot wear or use their&#xD;
      prostheses comfortably and increases their disability. The current standard surgical&#xD;
      treatment for a neuroma is to cut if off and bury the nerve ending in a muscle, to provide&#xD;
      cushioning when the neuroma grows back. Even though this is the best current treatment, it is&#xD;
      not always successful.&#xD;
&#xD;
      Even when a limb is amputated, the nerves that used to control that limb still carry messages&#xD;
      from the brain. Those messages are intended to tell the muscles how or when to move the&#xD;
      missing limb, but after amputation, these limb-control nerves are no longer connected to&#xD;
      muscles. In 2002, researchers at Northwestern Memorial Hospital in conjunction with the&#xD;
      Rehabilitation Institute of Chicago developed a new type of surgery called targeted muscle&#xD;
      reinnervation (TMR). In TMR, limb-control nerves are transferred so that they can control new&#xD;
      target muscles. The neuromas from the limb-control nerves are removed, then the small nerve&#xD;
      that controls the target muscle is cut. The two nerves are joined together so that the&#xD;
      limb-control nerve can then grow into, or reinnervate the target muscle. After TMR, when the&#xD;
      person tries to move the missing limb, the target muscle contracts instead and these signals&#xD;
      can be detected and used to control a prosthesis. TMR has now been done successfully almost&#xD;
      100 times worldwide. Interestingly, almost all of the patients who had painful neuromas&#xD;
      before TMR had no neuroma pain after surgery. This result was investigated in laboratory&#xD;
      studies - both rat and rabbit amputee neuromas were &quot;cured&quot; with TMR. We think that giving&#xD;
      the cut nerve endings somewhere to go and something to do prevents a neuroma from forming.&#xD;
&#xD;
      We plan to compare TMR versus the current standard surgical treatment for painful neuromas.&#xD;
      We will measure the effectiveness of both surgeries using an internet-based amputee pain&#xD;
      questionnaire. We will also use magnetic resolution imaging (MRI) to look at the nerves&#xD;
      before and after surgery. We have received a grant to complete a 4 year study in four&#xD;
      hospitals across the US, in around 200 patients, making this the largest neuroma study ever&#xD;
      performed. We expect that TMR will be significantly more effective for neuroma pain than the&#xD;
      standard treatment. This will change how patients with neuroma pain are treated and help&#xD;
      thousands of patients with amputations.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">January 1, 2018</completion_date>
  <primary_completion_date type="Actual">January 1, 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Improvement in pain of the amputated limb after surgery</measure>
    <time_frame>12 months</time_frame>
    <description>Difference in patient-reported pain scores before and after surgical treatment using the online survey tool.&#xD;
Compare patient-reported pre-operative survey results to those after surgical intervention at intervals over time (1 month, 3 months,6 months, 9 months,1 year, and then every six months thereafter until the conclusion of the study).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Improvement in physical functioning, including prosthesis wear, after surgery</measure>
    <time_frame>12 months</time_frame>
    <description>Using the same PROMIS platform, general health, physical functioning (including functional prosthesis wear), and satisfaction following surgery will also be assessed as important secondary outcomes, resulting in a more comprehensive and objective understanding of the effects of the two surgical approaches on neuroma pain.&#xD;
Another particularly useful tool for this study is the Orthotics and Prosthetics User Survey (OPUS) Functional Status. The OPUS is a validated instrument that assesses how well patients are using their prostheses. Thus, we will examine a very important secondary measure of neuroma pain-the ability to use a prosthesis. Prosthesis use is often the primary problem for individuals with painful neuromas; they hurt most during walking with a prosthesis or when wearing a prosthetic arm. Thus we expect OPUS to be a useful additional measure for quantifying the outcomes of the two types of neuroma surgeries</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Using MRI as a tool to determine if targeted muscle reinnervation prevents neuroma recurrence</measure>
    <time_frame>1 year</time_frame>
    <description>In our study, pre- and post-operative neuroma size (at one year) will be quantified using MRI scans. Pre-operative MRI measurements will be compared to the removed neuroma specimen to verify the accuracy of the modality. Post-operative MRI measurements will be used to assess whether a neuroma recurred at the site of the surgery and to determine the size of any new lesion.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">27</enrollment>
  <condition>Neuroma</condition>
  <condition>Neuroma Amputation</condition>
  <condition>Pain</condition>
  <arm_group>
    <arm_group_label>Traditional Traction Neurectomy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients will be randomized to either the current standard of care surgical treatment for neuromas (traction neurectomy) or the experimental intervention (targeted reinnervation). This arm involves the use of the current standard of care surgical treatment.&#xD;
Patients will undergo the same pre-operative evaluation, anesthesia, and dissection to identify the painful residual limb neuroma(s). In the active comparator arm, gentle traction will be applied to the nerve while excising the neuroma (traction neurectomy) allowing the nerve to retract more proximally. It may be buried in healthy muscle to further pad the nerve ending. The intention is to place the inevitable recurrent end-neuroma away from superficial locations in which it is likely to become mechanically irritated.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Targeted Muscle Reinnervation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will be randomized to either the current standard of care surgical treatment for neuromas (traction neurectomy) or the experimental intervention (targeted reinnervation). This arm involves the use of the experimental surgical treatment.&#xD;
Patients will undergo the same pre-operative evaluation, anesthesia, and dissection to identify the painful residual limb neuroma(s). Targeted muscle reinnervation involves transfer of residual nerves to otherwise redundant target muscles. Native motor innervation of the target muscle is cut, and the residual nerves-after excision of end-neuromas-are coapted to the motor end point of the motor nerve, close to its point of entry into the muscle.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Targeted Muscle Reinnervation</intervention_name>
    <arm_group_label>Targeted Muscle Reinnervation</arm_group_label>
    <other_name>Targeted Reinnervation</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Traction Neurectomy</intervention_name>
    <arm_group_label>Traditional Traction Neurectomy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult, 18 years or older: the Patient Reported Outcomes Measurement Information System&#xD;
             (PROMIS) questionnaire is not validated for pain-related evaluation in minors&#xD;
&#xD;
          -  An upper limb amputation above the wrist with or without a residual limb or a lower&#xD;
             limb amputation above the ankle with a residual limb (individuals with a hip&#xD;
             disarticulation amputation lack suitable target muscles for TR)&#xD;
&#xD;
          -  A neuroma within the residual limb: defined as patient-reported chronic localized pain&#xD;
             consistent with a physical exam that demonstrates that the pain is related to a cut&#xD;
             nerve and excludes other causes. There must be a supporting Tinel's sign on physical&#xD;
             exam, MRI findings suggestive of a neuroma, or localization of a neuroma by prior&#xD;
             intervention (surgical or otherwise) to distinguish the pain from phantom limb pain or&#xD;
             cold intolerance that are nonspecific signs of nerve damage that would not be affected&#xD;
             by treatment of a neuroma.&#xD;
&#xD;
          -  English or Spanish speaking: the PROMIS questionnaire is available in English and&#xD;
             parts are currently available in Spanish. The portions that are currently unavailable&#xD;
             in Spanish will be translated into Spanish for the purposes of this study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior TR Surgery: these patients have already had a procedure to improve their&#xD;
             prosthetic function and in these cases the nerves have been shortened. To perform a&#xD;
             second TR procedure with the previously shortened nerves would require a significant&#xD;
             proximal dissection and potentially greater soft tissue morbidity than the standard&#xD;
             treatment.&#xD;
&#xD;
          -  Cognitive impairment, due to TBI or other causes, sufficient to adversely affect&#xD;
             understanding of or compliance with study requirements, ability to respond to&#xD;
             questionnaires, or ability to give informed consent: The ability to understand and&#xD;
             comply with requirements of the study is essential in order for the study to generate&#xD;
             useable, reliable data. The ability to obtain relevant feedback through questionnaires&#xD;
             is essential to this study.&#xD;
&#xD;
          -  Pre-operative assessment that precludes the patient from being eligible for TR or&#xD;
             control surgery due to technical surgical concerns.&#xD;
&#xD;
          -  Significant other comorbidity: Any other medical issues or injuries that would&#xD;
             preclude safe administration of anesthesia or surgical intervention.&#xD;
&#xD;
          -  Participation in other ongoing studies related to neuropathic pain.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Northwestern University</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Walter Reed National Military Medical Center</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20889-5600</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Ohio State University</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Oklahoma Health Sciences Center</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>San Antonio Military Medical Center</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78234</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2018</verification_date>
  <study_first_submitted>July 23, 2014</study_first_submitted>
  <study_first_submitted_qc>July 29, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 31, 2014</study_first_posted>
  <last_update_submitted>January 1, 2018</last_update_submitted>
  <last_update_submitted_qc>January 1, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">January 3, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Northwestern University</investigator_affiliation>
    <investigator_full_name>Gregory Dumanian</investigator_full_name>
    <investigator_title>Professor of Surgery, Plastic and Reconstructive Surgery</investigator_title>
  </responsible_party>
  <keyword>Neuroma</keyword>
  <keyword>Amputee</keyword>
  <keyword>Amputation Stump</keyword>
  <keyword>Assessment, Pain</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neuroma</mesh_term>
  </condition_browse>
  <!-- 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/NCT02205385
org study id: TMR Neuroma
secondary id: OR120021
nct id: NCT02205385
lead sponsor: 
collaborator: 
has dmc: No
Subjects are being asked to participate in this study because they have an arm or leg
      amputation and have developed pain related to a neuroma (an ongoing localized pain related to
      a cut nerve ending).

      We are studying two different types of surgery to treat the neuroma pain. Today there are
      many surgical options reported which often means that there is no one best treatment. The
      surgery that shows the best success so far, involves cutting out the scarred nerve ending
      (neuroma) and burying the freshly cut nerve ending in a nearby muscle. Recently, a new
      surgery has been developed called targeted reinnervation (TR). This surgery connects these
      cut nerve endings to nerves going into nearby nonfunctional muscles. This surgery was
      developed to allow amputees to have better prosthesis control. By chance, neuroma pain
      improved significantly with TR. We, therefore, are conducting this clinical trial to evaluate
      which of these two surgeries best treats neuroma pain. We will ask all participants to fill
      out a questionnaire both before and after surgery. This will help us understand how a neuroma
      affects the quality of life of amputees and will allow us to understand which surgery leads
      to the best improvement in neuroma pain.

      In order to confirm the presence and location of the neuroma before surgery, a magnetic
      resonance image (MRI) will be performed. Taking these pictures requires subjects to lie still
      for a short period of time but does not involve any invasive procedures. After surgery, the
      MRI will be done again, this time to see if the nerve shows signs of scarring.
Loss of an arm or leg is a significant injury that affects a person's job prospects, personal
      relationships, and overall quality of life. Approximately 25% of all amputees will develop
      chronic local pain in the remaining part of their amputated limb. This pain is caused by
      neuromas- disorganized nerve endings and scar tissue that form when an injured nerve tries to
      heal. Every cut nerve will develop a neuroma unless the two ends of the nerve can be
      rejoined. With limb amputation, the nerves are cut and one end is lost with the limb,
      preventing the nerve from repairing itself. Instead, the cut nerve ending forms a painful
      neuroma. Chronic pain from neuromas is a major reason that amputees cannot wear or use their
      prostheses comfortably and increases their disability. The current standard surgical
      treatment for a neuroma is to cut if off and bury the nerve ending in a muscle, to provide
      cushioning when the neuroma grows back. Even though this is the best current treatment, it is
      not always successful.

      Even when a limb is amputated, the nerves that used to control that limb still carry messages
      from the brain. Those messages are intended to tell the muscles how or when to move the
      missing limb, but after amputation, these limb-control nerves are no longer connected to
      muscles. In 2002, researchers at Northwestern Memorial Hospital in conjunction with the
      Rehabilitation Institute of Chicago developed a new type of surgery called targeted muscle
      reinnervation (TMR). In TMR, limb-control nerves are transferred so that they can control new
      target muscles. The neuromas from the limb-control nerves are removed, then the small nerve
      that controls the target muscle is cut. The two nerves are joined together so that the
      limb-control nerve can then grow into, or reinnervate the target muscle. After TMR, when the
      person tries to move the missing limb, the target muscle contracts instead and these signals
      can be detected and used to control a prosthesis. TMR has now been done successfully almost
      100 times worldwide. Interestingly, almost all of the patients who had painful neuromas
      before TMR had no neuroma pain after surgery. This result was investigated in laboratory
      studies - both rat and rabbit amputee neuromas were "cured" with TMR. We think that giving
      the cut nerve endings somewhere to go and something to do prevents a neuroma from forming.

      We plan to compare TMR versus the current standard surgical treatment for painful neuromas.
      We will measure the effectiveness of both surgeries using an internet-based amputee pain
      questionnaire. We will also use magnetic resolution imaging (MRI) to look at the nerves
      before and after surgery. We have received a grant to complete a 4 year study in four
      hospitals across the US, in around 200 patients, making this the largest neuroma study ever
      performed. We expect that TMR will be significantly more effective for neuroma pain than the
      standard treatment. This will change how patients with neuroma pain are treated and help
      thousands of patients with amputations.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: Improvement in pain of the amputated limb after surgery
time frame: 12 months
description: Difference in patient-reported pain scores before and after surgical treatment using the online survey tool.
Compare patient-reported pre-operative survey results to those after surgical intervention at intervals over time (1 month, 3 months,6 months, 9 months,1 year, and then every six months thereafter until the conclusion of the study).
measure: Improvement in physical functioning, including prosthesis wear, after surgery
time frame: 12 months
description: Using the same PROMIS platform, general health, physical functioning (including functional prosthesis wear), and satisfaction following surgery will also be assessed as important secondary outcomes, resulting in a more comprehensive and objective understanding of the effects of the two surgical approaches on neuroma pain.
Another particularly useful tool for this study is the Orthotics and Prosthetics User Survey (OPUS) Functional Status. The OPUS is a validated instrument that assesses how well patients are using their prostheses. Thus, we will examine a very important secondary measure of neuroma pain-the ability to use a prosthesis. Prosthesis use is often the primary problem for individuals with painful neuromas; they hurt most during walking with a prosthesis or when wearing a prosthetic arm. Thus we expect OPUS to be a useful additional measure for quantifying the outcomes of the two types of neuroma surgeries
measure: Using MRI as a tool to determine if targeted muscle reinnervation prevents neuroma recurrence
time frame: 1 year
description: In our study, pre- and post-operative neuroma size (at one year) will be quantified using MRI scans. Pre-operative MRI measurements will be compared to the removed neuroma specimen to verify the accuracy of the modality. Post-operative MRI measurements will be used to assess whether a neuroma recurred at the site of the surgery and to determine the size of any new lesion.
arm group label: Traditional Traction Neurectomy
arm group type: Active Comparator
description: Patients will be randomized to either the current standard of care surgical treatment for neuromas (traction neurectomy) or the experimental intervention (targeted reinnervation). This arm involves the use of the current standard of care surgical treatment.
Patients will undergo the same pre-operative evaluation, anesthesia, and dissection to identify the painful residual limb neuroma(s). In the active comparator arm, gentle traction will be applied to the nerve while excising the neuroma (traction neurectomy) allowing the nerve to retract more proximally. It may be buried in healthy muscle to further pad the nerve ending. The intention is to place the inevitable recurrent end-neuroma away from superficial locations in which it is likely to become mechanically irritated.
arm group label: Targeted Muscle Reinnervation
arm group type: Experimental
description: Patients will be randomized to either the current standard of care surgical treatment for neuromas (traction neurectomy) or the experimental intervention (targeted reinnervation). This arm involves the use of the experimental surgical treatment.
Patients will undergo the same pre-operative evaluation, anesthesia, and dissection to identify the painful residual limb neuroma(s). Targeted muscle reinnervation involves transfer of residual nerves to otherwise redundant target muscles. Native motor innervation of the target muscle is cut, and the residual nerves-after excision of end-neuromas-are coapted to the motor end point of the motor nerve, close to its point of entry into the muscle.
intervention type: Procedure
intervention name: Targeted Muscle Reinnervation
arm group label: Targeted Muscle Reinnervation
other name: Targeted Reinnervation
intervention type: Procedure
intervention name: Traction Neurectomy
arm group label: Traditional Traction Neurectomy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Northwestern University
investigator full name: Gregory Dumanian
investigator title: Professor of Surgery, Plastic and Reconstructive Surgery
mesh term: Neuroma