<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/NCT01704339</url>
  </required_header>
  <id_info>
    <org_study_id>GN12RE072</org_study_id>
    <secondary_id>2012-001586-32</secondary_id>
    <nct_id>NCT01704339</nct_id>
  </id_info>
  <brief_title>Qutenza for Critical Ischaemia in End Stage Renal Failure</brief_title>
  <official_title>The Role of Qutenza (Topical Capsaicin 8%) in Treating Neuropathic Pain From Critical Ischaemia in Patients With End-stage Renal Failure</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Emma Aitken</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>NHS Greater Glasgow and Clyde</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Critical ischaemia is pain at rest as the result of poor blood flow and lack of oxygen being&#xD;
      delivered to the tissues. It normally affects the hands and feet and can be very&#xD;
      debilitating. It is particularly common and difficult to treat in patients with end stage&#xD;
      renal failure&#xD;
&#xD;
      Patients with renal failure are often high risk of any operative intervention which might&#xD;
      help the pain. Often the only treatment options are painkillers. Unfortunately however, the&#xD;
      commonly used painkillers, for example morphine, are known to cause worse side effects in&#xD;
      patients with renal failure (drowsiness, confusion etc.&#xD;
&#xD;
      Qutenza (topical capsaicin 8%) is a new treatment made from chilli peppers which is applied&#xD;
      to the skin as a patch and works directly at the nerve endings in the skin to prevent pain.&#xD;
      It therefore should not have the systemic side effects of other drugs. It has been&#xD;
      demonstrated to be beneficial in other painful conditions for example post-shingles pain and&#xD;
      nerve pain from HIV. It has never been used for critical ischaemia before.&#xD;
&#xD;
      We propose to investigate the efficacy of Qutenza in treating patients with end stage renal&#xD;
      failure and painful ischaemia. We will recruit 20 patients with painful ischaemia and treat&#xD;
      them with Qutenza. We will follow them up for 12 weeks and monitor the change in their pain&#xD;
      scores.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Peripheral vascular disease is common in end-stage renal failure (ESRF) affecting 24-77% of&#xD;
      patients (Stack, 2005). Critical ischaemia (pain at rest caused by insufficient blood supply&#xD;
      to a limb) is notoriously difficult to treat in this patient group. Advanced disease and&#xD;
      extensive co-morbidities limit surgical revascularisation options of proximal vessels&#xD;
      (Blankensteijn et al., 1996) and calciphylaxis (a process of calcification within the small&#xD;
      vessels unique to patients with end-stage renal failure) has few effective treatments (Ng &amp;&#xD;
      Peng, 2011). Often the only treatment option is symptomatic relief with strong analgesics.&#xD;
&#xD;
      Effective pain relief in patients with end-stage renal failure can be difficult to achieve.&#xD;
      The active metabolites of many opiates are renally-excreted and side effects are more common&#xD;
      in patients with end-stage renal failure. In particular, confusion and drowsiness limit their&#xD;
      use. Similarly drugs commonly used for neuropathic pain, such as gabapentin, have not be&#xD;
      investigated in clinical trials in patients with end-stage renal failure (Kurella et al.,&#xD;
      1993).&#xD;
&#xD;
      A drug which is not renally excreted, has minimal systemic absorption and does not require&#xD;
      dose adjustment in renal failure, is an attractive treatment option for patients with renal&#xD;
      failure.&#xD;
&#xD;
      Qutenza (topical capsaicin 8%) is an advanced dermal application system designed for rapid&#xD;
      delivery of capsaicin into the skin. The high concentration of capsaicin results in&#xD;
      reversible desensitisation of TRPV-1 expressing cutaneous sensory nerve endings and reduction&#xD;
      in nerve fibre density in the epidermis (Noto et al., 2009). The resulting pain relief is&#xD;
      long-lasting (12 weeks after a single application) (Backonja et al., 2008); Simpson et al.,&#xD;
      2008). Previous phase III studies have demonstrated a significant reduction in neuropathic&#xD;
      pain in patients with post-herpetic neuralgia (Blonsky et al., 2009) and HIV neuropathy (Noto&#xD;
      et al., 2099; Simpson et al., 2008) with a good tolerability profile and it is now licensed&#xD;
      for use in treatment of neuropathic pain in these patient groups.&#xD;
&#xD;
      The efficacy and tolerability of Qutenza (topical capsaicin 8%) has been evaluated in over&#xD;
      1,600 patients within clinical trials, with a reduction in pain scores at 8 weeks from 30-32%&#xD;
      to 20-24% compared to an active control (capsaicin 0.04%) (Simpson et al., 2008). Patients&#xD;
      frequently developed mild irritant symptoms of erythema and itch at the site of application,&#xD;
      but significant side effects of blistering were rare occurring in &lt;5%.&#xD;
&#xD;
      Currently Qutenza (topical capsaicin 8%) is not licensed for the treatment of diabetics&#xD;
      however there is evidence from a moderate number of diabetics enrolled into clinical trials&#xD;
      that Qutenza is both safe and effective in this patient group also. Webster et al, (2011)&#xD;
      treated a total of 91 patients with painful diabetic nephropathy and found a 31.5% reduction&#xD;
      in mean pain scores during weeks 2-12 post treatment. There was no difference in the&#xD;
      incidence of local side effects experienced by diabetics and non-diabetics (Backonja et al,&#xD;
      2011). One patient did develop an ulcer in the area of treatment however it is unclear&#xD;
      whether this related to the treatment or not (Webster et al, 2011).&#xD;
&#xD;
      Diabetic patients will be enrolled into this trial due to the frequency of diabetic patients&#xD;
      with renal failure and the contributing role of diabetes in small vessel disease leading to&#xD;
      critical ischaemia. The distinction between painful diabetic neuropathy and digital critical&#xD;
      ischaemia can be difficult to make clinically and it may be that a small proportion of&#xD;
      patients recruited for this study also have an element of diabetic neuropathy in addition to&#xD;
      their critical ischaemia. In view of the concern with ulceration of the feet in diabetics&#xD;
      treated with Qutenza, patients with diabetic neuropathy causing a loss of sensation will be&#xD;
      excluded from having their feet treated.&#xD;
&#xD;
      Pain from critical ischaemia is multi-modal and notoriously difficult to treat particularly&#xD;
      in patients with established renal failure in whom other analgesic agents are poorly&#xD;
      tolerated. A drug such as Qutenza (topical capsaicin 8%) which is not renally excreted, has&#xD;
      minimal systemic absorption and does not require dose adjustment in renal failure, is an&#xD;
      attractive treatment option for patients with renal failure.&#xD;
&#xD;
      This is a single centre, prospective observational trial evaluating efficacy and tolerability&#xD;
      of Qutenza (topical capsaicin 8%) for the treatment of digital critical ischaemia in patients&#xD;
      with end stage renal failure.&#xD;
&#xD;
      Primary Objective:&#xD;
&#xD;
      • To evaluate the safety and efficacy of Qutenza (topical capsaicin 8%) in relieving chronic&#xD;
      neuropathic pain from digital critical ischaemia in patients with end stage renal failure&#xD;
&#xD;
      Secondary objective:&#xD;
&#xD;
      • To evaluate Quality of Life (QoL) measures in patients with end stage renal failure who&#xD;
      have chronic neuropathic pain from critical ischaemia treated with Qutenza (topical capsaicin&#xD;
      8%)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>December 2012</start_date>
  <completion_date type="Anticipated">March 2014</completion_date>
  <primary_completion_date type="Anticipated">December 2013</primary_completion_date>
  <phase>Phase 4</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>Chronic neuropathic pain</measure>
    <time_frame>12 weeks</time_frame>
    <description>Chronic neuropathic pain as assessed by Visual Analogue Pain Score</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Neuropathic pain</measure>
    <time_frame>12 weeks</time_frame>
    <description>As assessed by Brief Pain Inventory</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life</measure>
    <time_frame>6 weeks, 12 weeks</time_frame>
    <description>Assessed using EQ-5D score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neuropathic pain</measure>
    <time_frame>1 week, 6 weeks</time_frame>
    <description>As assesses by Visual Analogue Pain Score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life</measure>
    <time_frame>12 weeks</time_frame>
    <description>As assessed by Patient Global Impression of Change score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety and tolerability</measure>
    <time_frame>1 day, 12 weeks</time_frame>
    <description>Skin will be assessed for breaks/ blisters and tolerability including the need for rescue analgesia will be recorded</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>End Stage Renal Failure</condition>
  <condition>Neuropathic Pain</condition>
  <arm_group>
    <arm_group_label>QUTENZA</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single treatment with QUTENZA (topical capsaicin 8%) transdermal patch</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>QUTENZA</intervention_name>
    <description>Single treatment with topical capsaicin 8%</description>
    <arm_group_label>QUTENZA</arm_group_label>
    <other_name>Topical capsaicin 8%</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All adult patients &gt; 18 years old with end stage renal disease on dialysis and&#xD;
             critical ischaemia defined as rest pain most days for &gt;3 months&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pre-dialysis&#xD;
&#xD;
          -  Hypersensitivity to Qutenza, Emla or any of the excipients&#xD;
&#xD;
          -  Broken skin or active ulceration at the site of application&#xD;
&#xD;
          -  Severe uncontrolled hypertension (systolic BP &gt;200)&#xD;
&#xD;
          -  Proven cardiac event during the preceding 3 months&#xD;
&#xD;
          -  Women who are pregnant or breast feeding&#xD;
&#xD;
          -  Diabetic neuropathy resulting in a loss of sensation&#xD;
&#xD;
          -  Lack of capacity or inability to provide informed consent&#xD;
&#xD;
          -  Declines participation in the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Emma L Aitken, MBChB</last_name>
    <role>Principal Investigator</role>
    <affiliation>NHS Greater Glasgow and Clyde</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Emma L Aitken, MBChB</last_name>
    <phone>01412111750</phone>
    <email>EmmaAitken@nhs.net</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>David B Kingsmore, MBChB FRCS</last_name>
    <phone>01412111750</phone>
    <email>david.kinsgmore@ggc.scot.nhs.uk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Department of Renal Surgery, Western Infirmary</name>
      <address>
        <city>Glasgow</city>
        <zip>G116NY</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <contact>
      <last_name>Emma L Aitken, MBChB</last_name>
      <phone>01412117150</phone>
      <email>EmmaAitken@nhs.net</email>
    </contact>
    <contact_backup>
      <last_name>David B Kingsmore, MBChB FRCS</last_name>
      <phone>01412111750</phone>
      <email>david.kingsmore@ggc.scot.nhs.uk</email>
    </contact_backup>
    <investigator>
      <last_name>Emma L Aitken, MBChB</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>David B Kingsmore, MBChB FRCS</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>October 2012</verification_date>
  <study_first_submitted>October 8, 2012</study_first_submitted>
  <study_first_submitted_qc>October 8, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 11, 2012</study_first_posted>
  <last_update_submitted>October 8, 2012</last_update_submitted>
  <last_update_submitted_qc>October 8, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 11, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>NHS Greater Glasgow and Clyde</investigator_affiliation>
    <investigator_full_name>Emma Aitken</investigator_full_name>
    <investigator_title>Clinical Research Fellow, Renal Surgery</investigator_title>
  </responsible_party>
  <keyword>End stage renal failure</keyword>
  <keyword>Neuropathic pain</keyword>
  <keyword>Critical digital ischaemia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neuralgia</mesh_term>
    <mesh_term>Renal Insufficiency</mesh_term>
    <mesh_term>Kidney Failure, Chronic</mesh_term>
    <mesh_term>Ischemia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Capsaicin</mesh_term>
  </intervention_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/NCT01704339
org study id: GN12RE072
secondary id: 2012-001586-32
nct id: NCT01704339
lead sponsor: 
has dmc: No
Critical ischaemia is pain at rest as the result of poor blood flow and lack of oxygen being
      delivered to the tissues. It normally affects the hands and feet and can be very
      debilitating. It is particularly common and difficult to treat in patients with end stage
      renal failure

      Patients with renal failure are often high risk of any operative intervention which might
      help the pain. Often the only treatment options are painkillers. Unfortunately however, the
      commonly used painkillers, for example morphine, are known to cause worse side effects in
      patients with renal failure (drowsiness, confusion etc.

      Qutenza (topical capsaicin 8%) is a new treatment made from chilli peppers which is applied
      to the skin as a patch and works directly at the nerve endings in the skin to prevent pain.
      It therefore should not have the systemic side effects of other drugs. It has been
      demonstrated to be beneficial in other painful conditions for example post-shingles pain and
      nerve pain from HIV. It has never been used for critical ischaemia before.

      We propose to investigate the efficacy of Qutenza in treating patients with end stage renal
      failure and painful ischaemia. We will recruit 20 patients with painful ischaemia and treat
      them with Qutenza. We will follow them up for 12 weeks and monitor the change in their pain
      scores.
Peripheral vascular disease is common in end-stage renal failure (ESRF) affecting 24-77% of
      patients (Stack, 2005). Critical ischaemia (pain at rest caused by insufficient blood supply
      to a limb) is notoriously difficult to treat in this patient group. Advanced disease and
      extensive co-morbidities limit surgical revascularisation options of proximal vessels
      (Blankensteijn et al., 1996) and calciphylaxis (a process of calcification within the small
      vessels unique to patients with end-stage renal failure) has few effective treatments (Ng &
      Peng, 2011). Often the only treatment option is symptomatic relief with strong analgesics.

      Effective pain relief in patients with end-stage renal failure can be difficult to achieve.
      The active metabolites of many opiates are renally-excreted and side effects are more common
      in patients with end-stage renal failure. In particular, confusion and drowsiness limit their
      use. Similarly drugs commonly used for neuropathic pain, such as gabapentin, have not be
      investigated in clinical trials in patients with end-stage renal failure (Kurella et al.,
      1993).

      A drug which is not renally excreted, has minimal systemic absorption and does not require
      dose adjustment in renal failure, is an attractive treatment option for patients with renal
      failure.

      Qutenza (topical capsaicin 8%) is an advanced dermal application system designed for rapid
      delivery of capsaicin into the skin. The high concentration of capsaicin results in
      reversible desensitisation of TRPV-1 expressing cutaneous sensory nerve endings and reduction
      in nerve fibre density in the epidermis (Noto et al., 2009). The resulting pain relief is
      long-lasting (12 weeks after a single application) (Backonja et al., 2008); Simpson et al.,
      2008). Previous phase III studies have demonstrated a significant reduction in neuropathic
      pain in patients with post-herpetic neuralgia (Blonsky et al., 2009) and HIV neuropathy (Noto
      et al., 2099; Simpson et al., 2008) with a good tolerability profile and it is now licensed
      for use in treatment of neuropathic pain in these patient groups.

      The efficacy and tolerability of Qutenza (topical capsaicin 8%) has been evaluated in over
      1,600 patients within clinical trials, with a reduction in pain scores at 8 weeks from 30-32%
      to 20-24% compared to an active control (capsaicin 0.04%) (Simpson et al., 2008). Patients
      frequently developed mild irritant symptoms of erythema and itch at the site of application,
      but significant side effects of blistering were rare occurring in <5%.

      Currently Qutenza (topical capsaicin 8%) is not licensed for the treatment of diabetics
      however there is evidence from a moderate number of diabetics enrolled into clinical trials
      that Qutenza is both safe and effective in this patient group also. Webster et al, (2011)
      treated a total of 91 patients with painful diabetic nephropathy and found a 31.5% reduction
      in mean pain scores during weeks 2-12 post treatment. There was no difference in the
      incidence of local side effects experienced by diabetics and non-diabetics (Backonja et al,
      2011). One patient did develop an ulcer in the area of treatment however it is unclear
      whether this related to the treatment or not (Webster et al, 2011).

      Diabetic patients will be enrolled into this trial due to the frequency of diabetic patients
      with renal failure and the contributing role of diabetes in small vessel disease leading to
      critical ischaemia. The distinction between painful diabetic neuropathy and digital critical
      ischaemia can be difficult to make clinically and it may be that a small proportion of
      patients recruited for this study also have an element of diabetic neuropathy in addition to
      their critical ischaemia. In view of the concern with ulceration of the feet in diabetics
      treated with Qutenza, patients with diabetic neuropathy causing a loss of sensation will be
      excluded from having their feet treated.

      Pain from critical ischaemia is multi-modal and notoriously difficult to treat particularly
      in patients with established renal failure in whom other analgesic agents are poorly
      tolerated. A drug such as Qutenza (topical capsaicin 8%) which is not renally excreted, has
      minimal systemic absorption and does not require dose adjustment in renal failure, is an
      attractive treatment option for patients with renal failure.

      This is a single centre, prospective observational trial evaluating efficacy and tolerability
      of Qutenza (topical capsaicin 8%) for the treatment of digital critical ischaemia in patients
      with end stage renal failure.

      Primary Objective:

      • To evaluate the safety and efficacy of Qutenza (topical capsaicin 8%) in relieving chronic
      neuropathic pain from digital critical ischaemia in patients with end stage renal failure

      Secondary objective:

      • To evaluate Quality of Life (QoL) measures in patients with end stage renal failure who
      have chronic neuropathic pain from critical ischaemia treated with Qutenza (topical capsaicin
      8%)
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Chronic neuropathic pain
time frame: 12 weeks
description: Chronic neuropathic pain as assessed by Visual Analogue Pain Score
measure: Neuropathic pain
time frame: 12 weeks
description: As assessed by Brief Pain Inventory
measure: Quality of Life
time frame: 6 weeks, 12 weeks
description: Assessed using EQ-5D score
measure: Neuropathic pain
time frame: 1 week, 6 weeks
description: As assesses by Visual Analogue Pain Score
measure: Quality of Life
time frame: 12 weeks
description: As assessed by Patient Global Impression of Change score
measure: Safety and tolerability
time frame: 1 day, 12 weeks
description: Skin will be assessed for breaks/ blisters and tolerability including the need for rescue analgesia will be recorded
arm group label: QUTENZA
arm group type: Experimental
description: Single treatment with QUTENZA (topical capsaicin 8%) transdermal patch
intervention type: Drug
intervention name: QUTENZA
description: Single treatment with topical capsaicin 8%
arm group label: QUTENZA
other name: Topical capsaicin 8%
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Emma L Aitken, MBChB
role: Principal Investigator
affiliation: NHS Greater Glasgow and Clyde
last name: Emma L Aitken, MBChB
phone: 01412111750
email: EmmaAitken@nhs.net
last name: David B Kingsmore, MBChB FRCS
phone: 01412111750
email: david.kinsgmore@ggc.scot.nhs.uk
facility: 
contact: 
contact backup: 
investigator: 
investigator: 
country: United Kingdom
responsible party type: Sponsor-Investigator
investigator affiliation: NHS Greater Glasgow and Clyde
investigator full name: Emma Aitken
investigator title: Clinical Research Fellow, Renal Surgery
mesh term: Neuralgia
mesh term: Renal Insufficiency
mesh term: Kidney Failure, Chronic
mesh term: Ischemia
mesh term: Capsaicin