xml: <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/NCT06036043</url>
    </required_header>
    <id_info>
      <org_study_id>RegionSealand</org_study_id>
      <nct_id>NCT06036043</nct_id>
    </id_info>
    <brief_title>Botulinum Toxin for Chronic Neuropathic Pain</brief_title>
    <official_title>Botulinum Toxin for Chronic Neuropathic Pain - an Interventional Open Label Study at the Interdisciplinary Pain Center, Zealand University Hospital</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Region Zealand</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Region Zealand</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        Treatment of peripheral neuropathic pain with Botulinum Toxin (BoNT) has showed promising&#xD;
        results since the first study was released in 2001. Further research, however, is needed in&#xD;
        order to strengthen the treatment, and a number of questions are unanswered. This includes&#xD;
        which indication is the treatment the most effective, how should the treatment be&#xD;
        administered, what is the duration of the effect? This study is a prospective interventional&#xD;
        open label study, designed to assess the efficacy and safety of Botolinum toxin in the&#xD;
        treatment of chronic neuropathic pain.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Background:&#xD;
  &#xD;
        There are eight randomized controlled trials investigating the effectiveness of BoNT for&#xD;
        peripheral neuropathic pain. The indications in the studies include diabetic neuropathy,&#xD;
        post-herpetic neuropathy, and peripheral nerve injury. Overall, the studies indicate a&#xD;
        treatment effect that is significantly better than placebo. However, the studies are&#xD;
        relatively small, their outcome measures vary, making comparison difficult, and there is&#xD;
        considerable variation in the degree of pain reduction. The duration of the effect of BoNT&#xD;
        treatment varies greatly and has not been systematically studied. The current evidence&#xD;
        provides a promising background in the treatment of BoNT og neuropathic pain, but further&#xD;
        research and documentation are needed.&#xD;
  &#xD;
        At the Interdisciplinary Pain Center, Zealand University Hospital, BoNT treatment is already&#xD;
        used for patients with neuropathic pain, who do not respond to 1. and 2. line treatments.&#xD;
        This study will evaluate the efficacy of the treatment.&#xD;
  &#xD;
        Method:&#xD;
  &#xD;
        The objective of this study is to prospectively follow a one-year cohort and subsequently&#xD;
        conduct a follow-up of 7 months (three treatments) for patients initiating BoNT treatment.&#xD;
        The follow-up includes monitoring the treatment's effectiveness, duration, and recording&#xD;
        adverse reactions.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">August 1, 2023</start_date>
    <completion_date type="Anticipated">December 30, 2024</completion_date>
    <primary_completion_date type="Anticipated">November 1, 2024</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Cohort</observational_model>
      <time_perspective>Prospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Maximal pain intensity</measure>
      <time_frame>At 28 days, 4 months, and 7 months after initiating treatment with BoNT type A (Xeomin®).</time_frame>
      <description>Proportion of patients with clinically relevant reduction in maximum pain (last 24 hours) compared to baseline, assessed using the Numerical Rating Scale (NRS 0-10; Zero represents 'no pain at all' and the upper limit represents 'the worst pain ever possible'). A minimal important difference (MID) of NRS 1 is considered as clinically relevant.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>pain intensity at rest</measure>
      <time_frame>At 28 days, 4 months, and 7 months after initiating treatment with BoNT type A (Xeomin®)</time_frame>
      <description>Proportion of patients with clinically relevant reduction in average pain at rest (last 24 hours) compared to baseline, assessed using the Numerical Rating Scale (NRS 0-10). A MID of NRS 1 is considered as clinically relevant.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Frequency of serious adverse events</measure>
      <time_frame>Up to 7 months after initiating treatment</time_frame>
      <description>Frequency of serious adverse events (according to ICH-GCP definition).</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Frequency of serious adverse reactions</measure>
      <time_frame>Up to 7 months after initiating treatment</time_frame>
      <description>Frequency of serious adverse reactions (according to ICH-GCP definition).</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>EuroQol-5 Dimension (EQ-5D)</measure>
      <time_frame>At 28 days, 4 months, and 7 months after initiating treatment with BoNT type A (Xeomin®).</time_frame>
      <description>Change in health-related quality of life (EQ-5D) compared to baseline. EQ-5D includes pain evaluation using the visual analogue scale (VAS 0-100; Zero represents 'no pain at all' and the upper limit represents 'the worst pain ever possible')</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Neuropathic Pain Symptom Inventory (NPSI)</measure>
      <time_frame>At 28 days, 4 months, and 7 months after initiating treatment with BoNT type A (Xeomin®).</time_frame>
      <description>Change in neuropathic pain compared to baseline using the NPSI that evaluates 12 different symptoms according to a numerical rating scale from 0 to 10 (Zero represents 'no pain at all' and the upper limit represents 'the worst pain ever possible')</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Onset and duration</measure>
      <time_frame>At 28 days</time_frame>
      <description>Time from treatment before onset of effect and duration of effect</description>
    </secondary_outcome>
    <number_of_groups>1</number_of_groups>
    <enrollment type="Anticipated">12</enrollment>
    <condition>Neuralgia</condition>
    <condition>Chronic Pain</condition>
    <arm_group>
      <arm_group_label>Intervention group</arm_group_label>
      <description>Patients treated with Botulinum Toxin</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Botulinum toxin type A</intervention_name>
      <description>The treatment will be administered either as a) subcutaneous infiltration with BoNT, covering the painful area, identified as allodynia during sensory examination, or b) perineural injection corresponding to the peripheral nerve(s) innervating the area where the pain is localized.&#xD;
  100 IU Xeomin is mixed with 4 ml NaCl. Injections are performed with a 1.5 cm spacing. Maximum of 40 injections (200 IU).&#xD;
  100 IU of botulinum toxin is mixed with 10 ml NaCl. For administration around multiple nerves, 50-100 IU per nerve (maximum 300 IU).&#xD;
  The treatment will primarily be provided by the principal investigator, or an anesthesiologist specializing in nerve blocks.&#xD;
  The specific method will be determined on an individual basis.&#xD;
  If there is no effect after one to two treatments, the treatment will be considered ineffective and discontinued. A treatment interval of 3 months has been established in accordance with a previous larger study.</description>
      <arm_group_label>Intervention group</arm_group_label>
      <other_name>Xeomin</other_name>
    </intervention>
    <eligibility>
      <study_pop>
        <textblock>
          Patients with chronic neuropathic pain&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Condition of neuropathic pain verified by paraclinical examination or supported by&#xD;
               underlying diseases (e.g., diabetes or herpes zoster).&#xD;
  &#xD;
            -  The condition is characterized by allodynia, hyperalgesia, and/or neuralgiform&#xD;
               symptoms such as burning and stabbing pain.&#xD;
  &#xD;
            -  The affected area can be identified through objective examination with detection of&#xD;
               disturbances in touch using cotton swabs, pin-prick, and/or vibration&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Mixed etiology of pain not solely attributable to neuropathy (e.g., fibromyalgia and&#xD;
               neuropathy or nociceptive pain and neuropathy).&#xD;
  &#xD;
            -  Contraindication to BoNT treatment (allergy to the toxin).&#xD;
  &#xD;
            -  Pregnancy.&#xD;
  &#xD;
            -  Diseases where BoNT treatment is contraindicated, such as motor neuron diseases and&#xD;
               muscular dystrophy.&#xD;
  &#xD;
            -  Severe psychiatric disorder.&#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>Thomas Peter Enggaard, MD, PHD</last_name>
      <role>Study Director</role>
      <affiliation>Rigshospitalet, Denmark</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Ole Mathiesen, MD, PHD</last_name>
      <role>Study Director</role>
      <affiliation>University Hospital of Region Zealand</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Rune Frederiksen, MD</last_name>
      <phone>26802789</phone>
      <email>Rune@acamedia.org</email>
    </overall_contact>
    <location>
      <facility>
        <name>University Hospital of regions Zealand</name>
        <address>
          <city>Køge</city>
          <zip>4600</zip>
          <country>Denmark</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Rune Frederiksen</last_name>
        <phone>26802789</phone>
        <email>Rune@acamedia.org</email>
      </contact>
    </location>
    <location_countries>
      <country>Denmark</country>
    </location_countries>
    <reference>
      <citation>Monheit GD, Pickett A. AbobotulinumtoxinA: A 25-Year History. Aesthet Surg J. 2017 May 1;37(suppl_1):S4-S11. doi: 10.1093/asj/sjw284.</citation>
      <PMID>28388718</PMID>
    </reference>
    <reference>
      <citation>Egeo G, Fofi L, Barbanti P. Botulinum Neurotoxin for the Treatment of Neuropathic Pain. Front Neurol. 2020 Aug 11;11:716. doi: 10.3389/fneur.2020.00716. eCollection 2020.</citation>
      <PMID>32849195</PMID>
    </reference>
    <reference>
      <citation>Datta Gupta A, Edwards S, Smith J, Snow J, Visvanathan R, Tucker G, Wilson D. A Systematic Review and Meta-Analysis of Efficacy of Botulinum Toxin A for Neuropathic Pain. Toxins (Basel). 2022 Jan 3;14(1):36. doi: 10.3390/toxins14010036.</citation>
      <PMID>35051013</PMID>
    </reference>
    <reference>
      <citation>Meyer-Friessem CH, Eitner LB, Kaisler M, Maier C, Vollert J, Westermann A, Zahn PK, Avila Gonzalez CA. Perineural injection of botulinum toxin-A in painful peripheral nerve injury - a case series: pain relief, safety, sensory profile and sample size recommendation. Curr Med Res Opin. 2019 Oct;35(10):1793-1803. doi: 10.1080/03007995.2019.1626228. Epub 2019 Jul 9.</citation>
      <PMID>31148462</PMID>
    </reference>
    <reference>
      <citation>Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, Dworkin RH, Gilron I, Haanpaa M, Hansson P, Jensen TS, Kamerman PR, Lund K, Moore A, Raja SN, Rice AS, Rowbotham M, Sena E, Siddall P, Smith BH, Wallace M. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015 Feb;14(2):162-73. doi: 10.1016/S1474-4422(14)70251-0. Epub 2015 Jan 7.</citation>
      <PMID>25575710</PMID>
    </reference>
    <reference>
      <citation>Lippi L, de Sire A, Folli A, D'Abrosca F, Grana E, Baricich A, Carda S, Invernizzi M. Multidimensional Effectiveness of Botulinum Toxin in Neuropathic Pain: A Systematic Review of Randomized Clinical Trials. Toxins (Basel). 2022 Apr 27;14(5):308. doi: 10.3390/toxins14050308.</citation>
      <PMID>35622555</PMID>
    </reference>
    <reference>
      <citation>Attal N, de Andrade DC, Adam F, Ranoux D, Teixeira MJ, Galhardoni R, Raicher I, Uceyler N, Sommer C, Bouhassira D. Safety and efficacy of repeated injections of botulinum toxin A in peripheral neuropathic pain (BOTNEP): a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2016 May;15(6):555-65. doi: 10.1016/S1474-4422(16)00017-X. Epub 2016 Mar 2.</citation>
      <PMID>26947719</PMID>
    </reference>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 14, 2023</study_first_submitted>
    <study_first_submitted_qc>September 11, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 13, 2023</study_first_posted>
    <last_update_submitted>September 11, 2023</last_update_submitted>
    <last_update_submitted_qc>September 11, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 13, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Region Zealand</investigator_affiliation>
      <investigator_full_name>Rune Frederiksen</investigator_full_name>
      <investigator_title>Principal Investigator</investigator_title>
    </responsible_party>
    <keyword>Botulinum Toxin</keyword>
    <keyword>chronic pain</keyword>
    <keyword>neuropathic pain</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Neuralgia</mesh_term>
      <mesh_term>Chronic Pain</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Botulinum Toxins</mesh_term>
      <mesh_term>Botulinum Toxins, Type A</mesh_term>
      <mesh_term>abobotulinumtoxinA</mesh_term>
    </intervention_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06036043
  org study id: RegionSealand
  nct id: NCT06036043
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  Treatment of peripheral neuropathic pain with Botulinum Toxin (BoNT) has showed promising
        results since the first study was released in 2001. Further research, however, is needed in
        order to strengthen the treatment, and a number of questions are unanswered. This includes
        which indication is the treatment the most effective, how should the treatment be
        administered, what is the duration of the effect? This study is a prospective interventional
        open label study, designed to assess the efficacy and safety of Botolinum toxin in the
        treatment of chronic neuropathic pain.
  Background:
  
        There are eight randomized controlled trials investigating the effectiveness of BoNT for
        peripheral neuropathic pain. The indications in the studies include diabetic neuropathy,
        post-herpetic neuropathy, and peripheral nerve injury. Overall, the studies indicate a
        treatment effect that is significantly better than placebo. However, the studies are
        relatively small, their outcome measures vary, making comparison difficult, and there is
        considerable variation in the degree of pain reduction. The duration of the effect of BoNT
        treatment varies greatly and has not been systematically studied. The current evidence
        provides a promising background in the treatment of BoNT og neuropathic pain, but further
        research and documentation are needed.
  
        At the Interdisciplinary Pain Center, Zealand University Hospital, BoNT treatment is already
        used for patients with neuropathic pain, who do not respond to 1. and 2. line treatments.
        This study will evaluate the efficacy of the treatment.
  
        Method:
  
        The objective of this study is to prospectively follow a one-year cohort and subsequently
        conduct a follow-up of 7 months (three treatments) for patients initiating BoNT treatment.
        The follow-up includes monitoring the treatment's effectiveness, duration, and recording
        adverse reactions.
  observational model: Cohort
  time perspective: Prospective
  measure: Maximal pain intensity
  time frame: At 28 days, 4 months, and 7 months after initiating treatment with BoNT type A (Xeomin®).
  description: Proportion of patients with clinically relevant reduction in maximum pain (last 24 hours) compared to baseline, assessed using the Numerical Rating Scale (NRS 0-10; Zero represents 'no pain at all' and the upper limit represents 'the worst pain ever possible'). A minimal important difference (MID) of NRS 1 is considered as clinically relevant.
  measure: pain intensity at rest
  time frame: At 28 days, 4 months, and 7 months after initiating treatment with BoNT type A (Xeomin®)
  description: Proportion of patients with clinically relevant reduction in average pain at rest (last 24 hours) compared to baseline, assessed using the Numerical Rating Scale (NRS 0-10). A MID of NRS 1 is considered as clinically relevant.
  measure: Frequency of serious adverse events
  time frame: Up to 7 months after initiating treatment
  description: Frequency of serious adverse events (according to ICH-GCP definition).
  measure: Frequency of serious adverse reactions
  time frame: Up to 7 months after initiating treatment
  description: Frequency of serious adverse reactions (according to ICH-GCP definition).
  measure: EuroQol-5 Dimension (EQ-5D)
  time frame: At 28 days, 4 months, and 7 months after initiating treatment with BoNT type A (Xeomin®).
  description: Change in health-related quality of life (EQ-5D) compared to baseline. EQ-5D includes pain evaluation using the visual analogue scale (VAS 0-100; Zero represents 'no pain at all' and the upper limit represents 'the worst pain ever possible')
  measure: Neuropathic Pain Symptom Inventory (NPSI)
  time frame: At 28 days, 4 months, and 7 months after initiating treatment with BoNT type A (Xeomin®).
  description: Change in neuropathic pain compared to baseline using the NPSI that evaluates 12 different symptoms according to a numerical rating scale from 0 to 10 (Zero represents 'no pain at all' and the upper limit represents 'the worst pain ever possible')
  measure: Onset and duration
  time frame: At 28 days
  description: Time from treatment before onset of effect and duration of effect
  arm group label: Intervention group
  description: Patients treated with Botulinum Toxin
  intervention type: Drug
  intervention name: Botulinum toxin type A
  description: The treatment will be administered either as a) subcutaneous infiltration with BoNT, covering the painful area, identified as allodynia during sensory examination, or b) perineural injection corresponding to the peripheral nerve(s) innervating the area where the pain is localized.
  100 IU Xeomin is mixed with 4 ml NaCl. Injections are performed with a 1.5 cm spacing. Maximum of 40 injections (200 IU).
  100 IU of botulinum toxin is mixed with 10 ml NaCl. For administration around multiple nerves, 50-100 IU per nerve (maximum 300 IU).
  The treatment will primarily be provided by the principal investigator, or an anesthesiologist specializing in nerve blocks.
  The specific method will be determined on an individual basis.
  If there is no effect after one to two treatments, the treatment will be considered ineffective and discontinued. A treatment interval of 3 months has been established in accordance with a previous larger study.
  arm group label: Intervention group
  other name: Xeomin
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Thomas Peter Enggaard, MD, PHD
  role: Study Director
  affiliation: Rigshospitalet, Denmark
  last name: Ole Mathiesen, MD, PHD
  role: Study Director
  affiliation: University Hospital of Region Zealand
  last name: Rune Frederiksen, MD
  phone: 26802789
  email: Rune@acamedia.org
  facility: 
  status: Recruiting
  contact: 
  country: Denmark
  citation: Monheit GD, Pickett A. AbobotulinumtoxinA: A 25-Year History. Aesthet Surg J. 2017 May 1;37(suppl_1):S4-S11. doi: 10.1093/asj/sjw284.
  PMID: 28388718
  citation: Egeo G, Fofi L, Barbanti P. Botulinum Neurotoxin for the Treatment of Neuropathic Pain. Front Neurol. 2020 Aug 11;11:716. doi: 10.3389/fneur.2020.00716. eCollection 2020.
  PMID: 32849195
  citation: Datta Gupta A, Edwards S, Smith J, Snow J, Visvanathan R, Tucker G, Wilson D. A Systematic Review and Meta-Analysis of Efficacy of Botulinum Toxin A for Neuropathic Pain. Toxins (Basel). 2022 Jan 3;14(1):36. doi: 10.3390/toxins14010036.
  PMID: 35051013
  citation: Meyer-Friessem CH, Eitner LB, Kaisler M, Maier C, Vollert J, Westermann A, Zahn PK, Avila Gonzalez CA. Perineural injection of botulinum toxin-A in painful peripheral nerve injury - a case series: pain relief, safety, sensory profile and sample size recommendation. Curr Med Res Opin. 2019 Oct;35(10):1793-1803. doi: 10.1080/03007995.2019.1626228. Epub 2019 Jul 9.
  PMID: 31148462
  citation: Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, Dworkin RH, Gilron I, Haanpaa M, Hansson P, Jensen TS, Kamerman PR, Lund K, Moore A, Raja SN, Rice AS, Rowbotham M, Sena E, Siddall P, Smith BH, Wallace M. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015 Feb;14(2):162-73. doi: 10.1016/S1474-4422(14)70251-0. Epub 2015 Jan 7.
  PMID: 25575710
  citation: Lippi L, de Sire A, Folli A, D'Abrosca F, Grana E, Baricich A, Carda S, Invernizzi M. Multidimensional Effectiveness of Botulinum Toxin in Neuropathic Pain: A Systematic Review of Randomized Clinical Trials. Toxins (Basel). 2022 Apr 27;14(5):308. doi: 10.3390/toxins14050308.
  PMID: 35622555
  citation: Attal N, de Andrade DC, Adam F, Ranoux D, Teixeira MJ, Galhardoni R, Raicher I, Uceyler N, Sommer C, Bouhassira D. Safety and efficacy of repeated injections of botulinum toxin A in peripheral neuropathic pain (BOTNEP): a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2016 May;15(6):555-65. doi: 10.1016/S1474-4422(16)00017-X. Epub 2016 Mar 2.
  PMID: 26947719
  responsible party type: Principal Investigator
  investigator affiliation: Region Zealand
  investigator full name: Rune Frederiksen
  investigator title: Principal Investigator
  mesh term: Neuralgia
  mesh term: Chronic Pain
  mesh term: Botulinum Toxins
  mesh term: Botulinum Toxins, Type A
  mesh term: abobotulinumtoxinA