<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/NCT02984072</url>
  </required_header>
  <id_info>
    <org_study_id>2015PQ01</org_study_id>
    <nct_id>NCT02984072</nct_id>
  </id_info>
  <brief_title>Menthol for PDT Pain Relief</brief_title>
  <acronym>MentholPDT</acronym>
  <official_title>A Randomised Double Blind, Placebo Controlled Study of the Efficacy of Topical Menthol for Pain Relief During Topical Photodynamic Therapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Dundee</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Dundee</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      Topical photodynamic therapy (PDT) is widely used to treat superficial non-melanoma skin&#xD;
      cancer (NMSC) and dysplasia, notably actinic keratosis and may also be effective in a range&#xD;
      of other dermatological conditions. A major limitation of PDT is pain during irradiation. A&#xD;
      lack of knowledge of the mechanism of PDT-induced pain has limited the development of&#xD;
      effective approaches for prevention or relief of this adverse effect. The investigators have&#xD;
      investigated the possible efficacy of menthol for PDT pain ex vivo and will now study this in&#xD;
      a clinical trial. This proposal describes the prospective randomised double blind, placebo&#xD;
      controlled clinical trial that will be undertaken to investigate the use of topical menthol&#xD;
      for PDT-induced pain relief in patients with actinic keratosis of the face and scalp who will&#xD;
      be attending general dermatology and PDT outpatient clinics at Ninewells Hospital, Dundee.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This proposal describes the prospective randomised double blind, placebo controlled clinical&#xD;
      trial that will be undertaken to investigate the use of topical menthol for PDT-induced pain&#xD;
      relief in patients with actinic keratosis of the face and scalp who will be attending general&#xD;
      dermatology and PDT outpatient clinics at Ninewells Hospital, Dundee.&#xD;
&#xD;
      This will be undertaken by comparison of 5% menthol in aqueous cream with aqueous cream as&#xD;
      placebo and the primary outcome measures will be pain recorded on a visual analogue scale&#xD;
      (VAS) during and up to 24 h after PDT. Secondary outcomes are phototoxicity, assessed by a&#xD;
      semi-quantitative scoring system immediately after PDT, fluorescence assessed routinely after&#xD;
      cream application and before irradiation and outcome based on clinical assessment three&#xD;
      months after PDT and patient evaluation. Patients will be involved in the study from the&#xD;
      first visit for PDT until the three-month assessment visit after PDT. Data analysis will be&#xD;
      undertaken using within-subject paired analyses as patients act as their own control.&#xD;
      Information from this study will inform investigators as to whether topical menthol should be&#xD;
      routinely incorporated into PDT treatment regimens in order to reduce pain and increase&#xD;
      tolerance of treatment. The information will also provide additional information as to the&#xD;
      mechanisms of PDT-induced pain and its possible prevention and/or relief.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 23, 2018</start_date>
  <completion_date type="Actual">October 10, 2019</completion_date>
  <primary_completion_date type="Actual">October 10, 2019</primary_completion_date>
  <phase>Phase 4</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pain immediately after PDT assessed by VAS score</measure>
    <time_frame>24h</time_frame>
    <description>pain immediately after and at 3, 6 and 24 h after PDT assessed by VAS score</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clearance: clear/partially clear/not clear - clinical assessment visually and by palpation</measure>
    <time_frame>3 months after treatment</time_frame>
    <description>Clearance (CR), partial clearance (PR) or no clearance (NR) will be recorded on each side in each participant</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Erythema (redness) (none/mild/moderate/severe)</measure>
    <time_frame>Immediately after PDT</time_frame>
    <description>Erythema grading (none/mild/moderate/severe) will be recorded on each side in each participant</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>fluorescence assessed as none/mild/moderate/strong using Wood's light examination</measure>
    <time_frame>Immediately before and after PDT</time_frame>
    <description>Fluorescence of each side in each participant will be recorded</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>patient preference - preferred right or left side or no preference</measure>
    <time_frame>24h</time_frame>
    <description>patient questionnaire completed at home and returned in SAE</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>swelling</measure>
    <time_frame>immediately after PDT</time_frame>
    <description>Swelling present or absent will be recorded on each side in each patient</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exudation</measure>
    <time_frame>immediately after PDT</time_frame>
    <description>Exudation present or absent will be recorded on each side in each patient</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>urticaria</measure>
    <time_frame>immediately after PDT</time_frame>
    <description>Urticaria present or absent will be recorded on each side in each patient</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Blinding - patient will be asked which side they think the menthol was used on or if they do not know</measure>
    <time_frame>24h</time_frame>
    <description>patient questionnaire completed at home and returned in SAE</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Actinic Keratosis</condition>
  <arm_group>
    <arm_group_label>Menthol</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>5% menthol in aqueous cream (Dermacool Forte)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Aqueous cream</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Menthol</intervention_name>
    <description>Topical menthol in aqueous cream</description>
    <arm_group_label>Menthol</arm_group_label>
    <other_name>5% menthol in aqueous cream</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aqueous Cream</intervention_name>
    <description>placebo</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>placebo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        A subject will be eligible for inclusion in this study only if all of the following&#xD;
        criteria apply:&#xD;
&#xD;
          1. Adults &gt;18 years. Target population is men or women ≥50 years (only post-menopausal&#xD;
             women)&#xD;
&#xD;
          2. Presence of actinic keratoses (AK) on the face and scalp involving both right and left&#xD;
             comparable sites.&#xD;
&#xD;
          3. Free of significant physical abnormalities (e.g. tattoos, dermatoses) in the potential&#xD;
             treatment area that may cause difficulty with examination or final evaluation.&#xD;
&#xD;
          4. Able to understand and adhere to protocol requirements.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Unable to give written informed consent.&#xD;
&#xD;
          2. Allergy to menthol, aqueous cream or excipients&#xD;
&#xD;
          3. Participation in a drug trial or other interventional study within 30 days of&#xD;
             recruitment to this study&#xD;
&#xD;
          4. Pre-menopausal women, pregnancy, breast feeding, planning to conceive&#xD;
&#xD;
          5. Chronic pain&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sally H Ibbotson, MBChB, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Dundee</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Ninewells Hospital and medical School</name>
      <address>
        <city>Dundee</city>
        <zip>DD1 9SY</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>November 3, 2016</study_first_submitted>
  <study_first_submitted_qc>December 1, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 6, 2016</study_first_posted>
  <last_update_submitted>March 3, 2021</last_update_submitted>
  <last_update_submitted_qc>March 3, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 9, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Keratosis, Actinic</mesh_term>
    <mesh_term>Keratosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Menthol</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Findings of study will be shared through peer reviewed publications and presentations, although individual participant data not disclosed</ipd_description>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>March 27, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/72/NCT02984072/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT02984072
org study id: 2015PQ01
nct id: NCT02984072
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Topical photodynamic therapy (PDT) is widely used to treat superficial non-melanoma skin
      cancer (NMSC) and dysplasia, notably actinic keratosis and may also be effective in a range
      of other dermatological conditions. A major limitation of PDT is pain during irradiation. A
      lack of knowledge of the mechanism of PDT-induced pain has limited the development of
      effective approaches for prevention or relief of this adverse effect. The investigators have
      investigated the possible efficacy of menthol for PDT pain ex vivo and will now study this in
      a clinical trial. This proposal describes the prospective randomised double blind, placebo
      controlled clinical trial that will be undertaken to investigate the use of topical menthol
      for PDT-induced pain relief in patients with actinic keratosis of the face and scalp who will
      be attending general dermatology and PDT outpatient clinics at Ninewells Hospital, Dundee.
This proposal describes the prospective randomised double blind, placebo controlled clinical
      trial that will be undertaken to investigate the use of topical menthol for PDT-induced pain
      relief in patients with actinic keratosis of the face and scalp who will be attending general
      dermatology and PDT outpatient clinics at Ninewells Hospital, Dundee.

      This will be undertaken by comparison of 5% menthol in aqueous cream with aqueous cream as
      placebo and the primary outcome measures will be pain recorded on a visual analogue scale
      (VAS) during and up to 24 h after PDT. Secondary outcomes are phototoxicity, assessed by a
      semi-quantitative scoring system immediately after PDT, fluorescence assessed routinely after
      cream application and before irradiation and outcome based on clinical assessment three
      months after PDT and patient evaluation. Patients will be involved in the study from the
      first visit for PDT until the three-month assessment visit after PDT. Data analysis will be
      undertaken using within-subject paired analyses as patients act as their own control.
      Information from this study will inform investigators as to whether topical menthol should be
      routinely incorporated into PDT treatment regimens in order to reduce pain and increase
      tolerance of treatment. The information will also provide additional information as to the
      mechanisms of PDT-induced pain and its possible prevention and/or relief.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Pain immediately after PDT assessed by VAS score
time frame: 24h
description: pain immediately after and at 3, 6 and 24 h after PDT assessed by VAS score
measure: Clearance: clear/partially clear/not clear - clinical assessment visually and by palpation
time frame: 3 months after treatment
description: Clearance (CR), partial clearance (PR) or no clearance (NR) will be recorded on each side in each participant
measure: Erythema (redness) (none/mild/moderate/severe)
time frame: Immediately after PDT
description: Erythema grading (none/mild/moderate/severe) will be recorded on each side in each participant
measure: fluorescence assessed as none/mild/moderate/strong using Wood's light examination
time frame: Immediately before and after PDT
description: Fluorescence of each side in each participant will be recorded
measure: patient preference - preferred right or left side or no preference
time frame: 24h
description: patient questionnaire completed at home and returned in SAE
measure: swelling
time frame: immediately after PDT
description: Swelling present or absent will be recorded on each side in each patient
measure: Exudation
time frame: immediately after PDT
description: Exudation present or absent will be recorded on each side in each patient
measure: urticaria
time frame: immediately after PDT
description: Urticaria present or absent will be recorded on each side in each patient
measure: Blinding - patient will be asked which side they think the menthol was used on or if they do not know
time frame: 24h
description: patient questionnaire completed at home and returned in SAE
arm group label: Menthol
arm group type: Active Comparator
description: 5% menthol in aqueous cream (Dermacool Forte)
arm group label: Placebo
arm group type: Placebo Comparator
description: Aqueous cream
intervention type: Drug
intervention name: Menthol
description: Topical menthol in aqueous cream
arm group label: Menthol
other name: 5% menthol in aqueous cream
intervention type: Drug
intervention name: Aqueous Cream
description: placebo
arm group label: Placebo
other name: placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: No
last name: Sally H Ibbotson, MBChB, MD
role: Principal Investigator
affiliation: University of Dundee
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Keratosis, Actinic
mesh term: Keratosis
mesh term: Menthol
sharing ipd: No
ipd description: Findings of study will be shared through peer reviewed publications and presentations, although individual participant data not disclosed
provided document: 