<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/NCT04428359</url>
  </required_header>
  <id_info>
    <org_study_id>IRC/1607/019</org_study_id>
    <secondary_id>858 - 2019</secondary_id>
    <nct_id>NCT04428359</nct_id>
  </id_info>
  <brief_title>A Comparative Study to Assess Efficacy of Intralesional MMR Vaccine and Intralesional Vitamin D3 in Treatment of Warts</brief_title>
  <acronym>MMR</acronym>
  <official_title>A Comparative Study to Assess Efficacy of Intralesional MMR (Measles, Mumps, Rubella) Vaccine and Intralesional Vitamin D3 in Treatment of Warts</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>B.P. Koirala Institute of Health Sciences</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Nepal Health Research Council</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>B.P. Koirala Institute of Health Sciences</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>
      Common warts are papulonodular epidermal lesions caused by human papillomavirus (HPV) usually&#xD;
      by the strains 1, 2, 4, 27 or 57. Cutaneous warts occur in 7% to 10% of the general&#xD;
      population, with a maximum incidence between 12 and 16 years. There are multiple destructive&#xD;
      treatment modalities of wart but they have many adverse effects. Hence immunotherapy is&#xD;
      becoming popular in treatment of warts. It is believed that the injection to the HPV-infected&#xD;
      tissue induces a strong nonspecific pro-inflammatory signal and attracts the&#xD;
      antigen-presenting cells. Which then promotes a Th1 cytokine response and leads to&#xD;
      delayed-type hypersensitivity reaction leading to the eradication of the HPV-infected cells.&#xD;
&#xD;
      We are undertaking a study to evaluate and compare the safety and efficacy of 2 such&#xD;
      immunotherapeutic agents namely, IL measles, mumps and rubella (MMR) vaccine versus IL&#xD;
      vitamin D3 for the treatment of warts.&#xD;
&#xD;
      RESEARCH HYPOTHESIS Null Hypotheses: IL MMR vaccine is not better than IL Vitamin D in the&#xD;
      treatment of wart Alternative hypothesis: IL MMR vaccine is better than IL Vitamin D in the&#xD;
      treatment of wart&#xD;
&#xD;
      Method: A total of 60 patients will be included in the study, 30 in each group. Group A and&#xD;
      Group B patients will be injected with 0.5 ml of IL MMR and 0.5 ml of IL vitamin D3&#xD;
      respectively into a single or a maximum of 5 warts at a time in case of multiple warts. The&#xD;
      IL injection will be given every 3 weeks for a maximum of 5 doses. Clinical assessment will&#xD;
      be done by taking photographs and measurements at baseline, before each treatment session,&#xD;
      and 3 months after the completion of treatment. The response will be evaluated by a decrease&#xD;
      in the size and number of the wart(s) and photographic comparison. The response will be&#xD;
      considered complete if there is a complete clearance of the wart(s), good if the wart(s) will&#xD;
      regress in size by 75-99%, moderate if they regress by 50-74% and no or mild if there will be&#xD;
      a 0-49% decrease in wart(s). Immediate and late side effects of MMR and Vitamin D will be&#xD;
      evaluated after each session. Follow up will be made monthly for 3 months to detect any&#xD;
      recurrence. Quality of life (QoL) will be measured in wart patients, using the Nepali version&#xD;
      of the dermatology life quality index (DLQI) questionnaire before initiation of treatment and&#xD;
      at the end of follow up.&#xD;
&#xD;
      Statistical analysis will be done using Statistical Package for the Social Sciences 10.5&#xD;
      version.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      INTRODUCTION Warts are common skin conditions resulting from infection of keratinocytes by&#xD;
      human papillomavirus (HPV). After infection of the basal layer, there is clonal proliferation&#xD;
      leading to epidermal thickening and hyperkeratinization and eventually results in a visible&#xD;
      wart. HPVs are ubiquitous, epitheliotropic non-enveloped small double-stranded DNA viruses.&#xD;
      Over 150 types of HPVs have been identified. Among them verruca vulgaris are usually caused&#xD;
      by HPV types 1, 2, 4, 27 or 57, and plane warts by HPV types 3 or 10.&#xD;
&#xD;
      Cutaneous warts occur in 7% to 10% of the general population, with a maximum incidence&#xD;
      between the ages of 12 and 16 years. In children, clearance can occur after only a few&#xD;
      months, with 50% at 1 year and about 65%-78% by 2 years. The rate of clearance is influenced&#xD;
      by factors like virus strain, host immune status, extent and duration of warts. The&#xD;
      transmission of warts occurs from direct contact or indirectly via fomites.&#xD;
&#xD;
      There are multiple destructive, antiproliferative and antiviral agents in treatment of warts.&#xD;
      Other modalities include hypnotherapy, acupuncture, local hyperthermia, therapeutic&#xD;
      vaccination and combinations of the previous agents. Destructive therapies usually come with&#xD;
      many adverse effects hence immunotherapy is becoming more popular, especially in the&#xD;
      treatment of refractory cutaneous and genital warts. These include various topical,&#xD;
      intralesional (IL) and systemic agents. IL Measles, Mumps, rubella (MMR) and IL vitamin D3&#xD;
      are examples of immunotherapeutic agents.&#xD;
&#xD;
      Immunotherapy is defined as a type of biological therapy that uses substances to stimulate or&#xD;
      suppress the immune system to help the body fight cancer, infection, and other diseases.&#xD;
      Immunotherapy can affect the immune system in general or can be cell-specific.&#xD;
&#xD;
      Immunotherapy is believed to induce a strong nonspecific pro-inflammatory signal and attract&#xD;
      the antigen-presenting cells. This is associated with the release of cytokines such as IL-2,&#xD;
      IL-8, IL-12, IL-I8, tumor necrosis factor-α, and interferon-γ. This then promotes a Th1&#xD;
      cytokine response which leads to the activation of delayed-type hypersensitivity reaction&#xD;
      leading to the eradication of the HPV-infected cells. Furthermore, the trauma of the&#xD;
      injection may also cause a resolution in previously sensitized individuals. Vitamin D3 is&#xD;
      also claimed to regulate epidermal cell differentiation and proliferation and may modulate&#xD;
      cytokine production through its action upon vitamin D receptors (VDRs). Since IL antigen&#xD;
      immunotherapy enhances recognition of the virus by the immune system it causes clearance of&#xD;
      both treated and untreated lesions and helps to prevent future clinical infection through&#xD;
      induction of long-term acquired immunity to HPV.&#xD;
&#xD;
      MMR vaccine is included in immunization schedule of Nepal so pre-sensitization skin test is&#xD;
      not needed as all patients are expected to be immune. The presence of 3 different antigens in&#xD;
      MMR increases the sensitivity to the injected antigen and decreases the likelihood of anergy.&#xD;
      Side effects of MMR include pain during injection, flu-like symptoms, pruritus and burning&#xD;
      sensation.&#xD;
&#xD;
      IL vitamin D is a novel addition to therapies in warts as it is a simple, effective,&#xD;
      well-tolerable, and inexpensive method with negligible local and systemic side effects. Side&#xD;
      effects of Vitamin D3 include transient mild to moderate pain, edema at the site of injection&#xD;
      and mild erythema. Additionally, it would be safer to monitor serum vitamin D and calcium&#xD;
      levels before and after intralesional vitamin D treatment to prevent possible&#xD;
      hypervitaminosis D.&#xD;
&#xD;
      RATIONALE Intralesional Immunotherapy is an emerging method of treatment of wart in which&#xD;
      injection in a single wart causes the resolution of distant warts as well. Compared to other&#xD;
      destructive modalities, it is more effective and comfortable for the patient as it obviates&#xD;
      the need for individual treatment of each wart. In addition it has a lower rate of&#xD;
      recurrence, avoids adverse effects such as scarring, is more cost-effective in multiple warts&#xD;
      and decreases the time a physician has to spend on each patient. Further both injection MMR&#xD;
      and Vitamin D3 are readily available as compared to other immunotherapeutic agents like&#xD;
      purified protein derivative and candida antigen.&#xD;
&#xD;
      IL MMR vaccine has been used for a longer time than IL vitamin D and there are more&#xD;
      comparative studies showing efficacy of MMR vaccine with rates of clearance ranging from&#xD;
      70.4% to 82.4%. The clearance rates for IL vitamin D ranges from 40% to 90%.&#xD;
&#xD;
      The advantages of vitamin D over MMR vaccine are cost-effectiveness, non-requirement of&#xD;
      maintenance of cold chain, easy availability, and feasibility of use in immunosuppressed&#xD;
      patients.&#xD;
&#xD;
      As per Institute of Medicine (IOM), the tolerable upper intake of vitamin D is 4000 IU/day&#xD;
      for anyone older than 9 years such that annual maximum dose will be 1,460,000 IU. The total&#xD;
      amount of vitamin D that we will be administering will be 1,500,000 IU. Furthermore, since we&#xD;
      are giving it intralesionally systemic absorption is likely to be low although data on exact&#xD;
      amount of IL vitamin D that gets absorbed systemically is not available. In other studies,&#xD;
      patients have been evaluated clinically for signs and symptoms of hypervitaminosis D however,&#xD;
      no signs of toxicity were observed.&#xD;
&#xD;
      As per our literature search,&#xD;
&#xD;
        1. No previous studies on immunotherapy in wart have been conducted in our country&#xD;
&#xD;
        2. No comparative studies have been done to compare IL MMR and IL vitamin D3 in treatment&#xD;
           of wart hence we aim to establish efficacy of each and compare the two.&#xD;
&#xD;
      OBJECTIVES&#xD;
&#xD;
      Primary Objectives:&#xD;
&#xD;
        1. To determine the efficacy of IL MMR vaccine in the treatment of Wart&#xD;
&#xD;
        2. To determine the efficacy of IL vitamin D in the treatment of wart&#xD;
&#xD;
        3. To compare the efficacy of IL MMR vaccine and IL Vitamin D&#xD;
&#xD;
      Secondary Objective:&#xD;
&#xD;
        1. To determine the clinical and demographic profile of patients with different types of&#xD;
           warts visiting Dermatology outpatient department(OPD) of BP Koirala Institute of Health&#xD;
           Sciences (BPKIHS)&#xD;
&#xD;
        2. To determine the side effects of IL MMR vaccine and IL Vitamin D in treatment of wart&#xD;
&#xD;
        3. To determine Dermatology life quality index (DLQI) in wart patients.&#xD;
&#xD;
      Operational definition Wart - clinical diagnosis made by a dermatologist Complete response&#xD;
      (100%)- Complete disappearance of warts including distant ones and skin texture at the site&#xD;
      is restored to normal Excellent response (75-99%)-Reduction in size and number including&#xD;
      distant ones and few residual warts still visible Good response (50-74%)-Some reduction in&#xD;
      size only including that of distant ones but no decrease in number of warts Poor or no&#xD;
      response (0-49%)-No significant change in size and number of warts Recurrence- Recurrence&#xD;
      during the study period&#xD;
&#xD;
      MATERIALS AND METHODOLOGY Materials: Study population will be all patients clinically&#xD;
      diagnosed with warts visiting the Dermatology OPD of BPKIHS, Dharan.&#xD;
&#xD;
      Study design: Prospective comparative longitudinal study Study Period: Probable duration of&#xD;
      the study will be 1 year after approval from the Institutional Review Committee (IRC) and&#xD;
      Nepal Health Research Council (NHRC) Ethical Clearance: Taken from IRC, BPKIHS and NHRC&#xD;
      Conflict of interest: None Sampling Technique: Census method with all consecutive patients&#xD;
      meeting inclusion criteria for initial 6 months Sample size The study considers a 95%&#xD;
      confidence interval, 80% power to estimate sample size. According to the literature review,&#xD;
      it was found that there was 84.6% and 40% improvement in MMR and Vitamin D respectively.&#xD;
&#xD;
      Now using the sample size estimation formula for 2 proportion {(Zα√2p(1-p)+ Z1-β√((p1(1-p1)&#xD;
      p2(1-p2)}2))/(p1-p2)2 Where n= sample size for each group p1 = 0.846 p2 = 0.40 p= (p1 +p2)/2&#xD;
      Zα=1.96 Z1-β = 1.28 Using above formula, n= 12.3 The formula for actual sample size is&#xD;
      n/4{1+√(1+4/n|p1-p2|)}2 na = 16.48 Adding 10% in calculated value to reduce bias sampling&#xD;
      technique, the minimum sample size in each group is 18.13 =19 Considering loss of follow up,&#xD;
      sample size in each group= 30 Total sample size= 60&#xD;
&#xD;
      Methodology Based on the computer generated random number table, patients satisfying&#xD;
      inclusion criteria will be assigned to either Group A or Group B once they come to OPD.&#xD;
      Informed consent will be taken and detailed information including personal data, past&#xD;
      history, medical history, drug history, clinical data like site, size, number and&#xD;
      distribution of lesions will be recorded in preset pro forma. Photographs of the lesions will&#xD;
      be taken before the first treatment session, in every treatment session and 3 months after&#xD;
      last session.&#xD;
&#xD;
      Group A Freeze-dried MMR vaccine single-use vials stored at 2°C-8°C will be reconstituted&#xD;
      with 0.5 mL of distilled water immediately before IL use. If reconstituted vaccine is not&#xD;
      used within 8 hours it must be discarded. All Group A patients will receive IL injection of&#xD;
      upto 0.5 mL of reconstituted MMR vaccine into a single or a maximum of 5 warts at a time in&#xD;
      case of multiple warts with 31 G insulin syringe with beveled edge facing upward. Amount of&#xD;
      injection on each wart will depend on the size of each wart. The injection will be given&#xD;
      every three weeks for a maximum of 5 doses.&#xD;
&#xD;
      Group B All Group B patients will receive a maximum of 0.5 mL Inj. Vitamin D3 (600,000 IU;&#xD;
      15mg/ml) in each session after injection of IL lignocaine with 31 G insulin syringe. In cases&#xD;
      of multiple warts, a maximum of 5 warts will be injected at a time. Amount of injection on&#xD;
      each wart will depend on the size of each wart. The session will be done at 3 weekly&#xD;
      intervals for a maximum of 5 sessions or until complete resolution of warts, whichever is&#xD;
      earlier. In patients of group B serum vitamin D level will be measured after 20 days of 3rd&#xD;
      dose and 1 month after the last dose to ensure safe monitoring.&#xD;
&#xD;
      Patient and physician global assessment using 'Visual Analog Scale score' and photographic&#xD;
      comparison will be used to assess the response to treatment as mentioned in operational&#xD;
      definition. Immediate and late adverse effects in both groups will be evaluated after each&#xD;
      treatment session. Necessary investigations and intervention will be done if needed. Follow&#xD;
      up will be made monthly for 3 months to detect any recurrence.&#xD;
&#xD;
      Quality of Life(QoL) QoL will be measured in wart patients, using the Nepali version of the&#xD;
      dermatology life quality index (DLQI) questionnaire before initiation of treatment and at the&#xD;
      end of follow up. DLQI contains 10 questions that involves 6 sections: symptoms and feelings,&#xD;
      daily activities, leisure, work and school, personal relationships and treatment. Questions 1&#xD;
      and 2 assess symptoms and feelings; 3 and 4, daily activities; 5 and 6, leisure; 7, work and&#xD;
      school; 8 and 9, personal relationships and 10, treatment. The clinically meaningful change&#xD;
      or reduction in the DLQI score is measured as the change in score from one band to the other.&#xD;
&#xD;
      Statistical analysis&#xD;
&#xD;
        1. Data handling: Data will be entered in Microsoft Excel 2010 and statistical analysis&#xD;
           will be done using Statistical Package for the Social Sciences 10.5 version&#xD;
&#xD;
        2. Coding: Alpha numerical code will be used&#xD;
&#xD;
        3. Monitoring: Data will be entered after every day of work and supervised by guide.&#xD;
&#xD;
        4. Statistical Analysis:&#xD;
&#xD;
             1. Chi square test to compare the categorical data between the groups.&#xD;
&#xD;
             2. Paired t test for comparing normally distributed continuous variables at different&#xD;
                time point within the group&#xD;
&#xD;
             3. Independent 't' test for comparing normally distributed continuous variables at&#xD;
                different time point between the groups&#xD;
&#xD;
             4. Wilcoxon signed rank test to compare the not normally distributed variables,&#xD;
                ordinal data&#xD;
&#xD;
             5. Mann- Whitney U test to compare the not normally distributed variables, ordinal&#xD;
                data.&#xD;
&#xD;
             6. Kaplan-Meier curves to compare the response rate on each follow up visit between&#xD;
                the groups.&#xD;
&#xD;
      Test of significance will be considered when value of p ≤ 0.05.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 1, 2020</start_date>
  <completion_date type="Actual">January 30, 2021</completion_date>
  <primary_completion_date type="Actual">January 15, 2021</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>
    <intervention_model_description>Group A - will receive IL MMR Group B- will receive IL Vitamin D3</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
    <masking_description>Only patients will be blinded to the randomization and intervention.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Efficacy of IL MMR and IL Vitamin D3 in Treatment of Warts</measure>
    <time_frame>Starting of treatment to end of three months follow-up after completing treatment</time_frame>
    <description>Percentage of patients showing complete response to IL MMR and IL Vitamin D3&#xD;
Complete response -Complete disappearance of warts including distant ones and skin texture at the site is restored to normal (100%) Excellent response- Reduction in size and number including distant ones and few residual warts still visible (75-99%) Good response- Some reduction in size only including that of distant ones but no decrease in number of warts (50-74%) Poor or no response- No significant change in size and number of warts (0-49%)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants in Each Education Level Group</measure>
    <time_frame>At the time of enrollment</time_frame>
    <description>Distribution of wart patients into different education level like professional degree, graduate, intermediate, high school, middle school, primary school or illiterate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants in Each Occupation Group</measure>
    <time_frame>At the time of enrollment</time_frame>
    <description>Number of participants with different occupations like professional, semiprofessional, clerical/shop/farm, skilled worker, semiskilled worker, unskilled worker, unemployed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration</measure>
    <time_frame>At the time of enrollment</time_frame>
    <description>Duration of warts</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of the Warts on Patient's Life as Assessed by Dermatological Life Quality Index</measure>
    <time_frame>At the time of enrollment and at the end of three months follow- up after completion of treatment</time_frame>
    <description>Quality of life (QoL) will be measured in wart patients, using the Nepali version of the dermatology life quality index (DLQI) questionnaire before initiation of treatment and at the end of follow up. DLQI contains 10 questions that involves 6 sections: symptoms and feelings, daily activities, leisure, work and school, personal relationships and treatment. Questions 1 and 2 assess symptoms and feelings; 3 and 4, daily activities; 5 and 6, leisure; 7, work and school; 8 and 9, personal relationships and 10, treatment.&#xD;
The DLQI consists of 10 questions. Each question is given 4 options from not at all effect (score 0) to very much effect (score 3). The minimum and maximum possible score, thus, is 0 and 30 respectively.&#xD;
Meaning of DLQI Scores 0-1 = no effect at all on patient's life 2-5 = small effect on patient's life 6-10 = moderate effect on patient's life 11-20 = very large effect on patient's life 21-30 = extremely large effect on patient's life&#xD;
.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Number of Warts</measure>
    <time_frame>At the time of enrollment</time_frame>
    <description>Number of warts in patients</description>
  </other_outcome>
  <other_outcome>
    <measure>Size</measure>
    <time_frame>At the time of enrollment</time_frame>
    <description>Size range of warts</description>
  </other_outcome>
  <other_outcome>
    <measure>Number of Participants With Each Progression Type</measure>
    <time_frame>At the time of enrollment</time_frame>
    <description>Number of participants with different progressions of warts like Gradual or rapid or stable or regressing lesions</description>
  </other_outcome>
  <other_outcome>
    <measure>Number of Participants Who Had Taken Past Treatment</measure>
    <time_frame>At the time of enrollment</time_frame>
    <description>Frequency of different types of past treatment taken- either traditional or medical treatments</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">66</enrollment>
  <condition>Verruca Viral</condition>
  <arm_group>
    <arm_group_label>Measles, Mumps, Rubella vaccine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All Group A patients will receive intralesional MMR.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Vitamin D3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All Group B patients will receive intralesional Vitamin D3</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Measles-Mumps-Rubella Vaccine</intervention_name>
    <description>Group A patients will receive intralesional injection of upto 0.5 mL of reconstituted MMR vaccine into a single or a maximum of 5 warts at a time in case of multiple warts. Intralesional injection will be given every three weeks for a maximum of 5 doses or until complete resolution, whichever is earlier.</description>
    <arm_group_label>Measles, Mumps, Rubella vaccine</arm_group_label>
    <other_name>MMR</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vit D</intervention_name>
    <description>Group B patients will receive a maximum of 0.5 mL Inj. Vitamin D3 (600,000 IU; 15mg/ml) in each session after injection of IL lignocaine with 31 G insulin syringe. In cases of multiple warts, a maximum of 5 warts will be injected at a time. The session will be done at 3 weekly intervals for a maximum of 5 sessions or until complete resolution of warts, whichever is earlier</description>
    <arm_group_label>Vitamin D3</arm_group_label>
    <other_name>Vitamin D3</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        1. Clinically diagnosed patients who have more than three warts or single wart in difficult&#xD;
        to treat sites (periungual, palms and soles)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients not under any systemic or topical treatment of warts for the last four weeks&#xD;
&#xD;
          2. Patients with a past history of an allergic response to MMR or any other vaccine or&#xD;
             Vitamin D&#xD;
&#xD;
          3. Patients with current acute febrile illness or any bacterial infection&#xD;
&#xD;
          4. Immunosuppressed patients&#xD;
&#xD;
          5. Pregnant or lactating women&#xD;
&#xD;
          6. Patients having a past history of asthma, allergic skin disorders or convulsions&#xD;
&#xD;
          7. Patients with keloidal tendency&#xD;
&#xD;
          8. Patient refusal for consent&#xD;
&#xD;
          9. Treating physician's decision to give other treatment modality&#xD;
&#xD;
         10. Patients with hypervitaminosis D, muscle weakness, bone pain, altered sensorium&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bibisha Baaniya, MBBS</last_name>
    <role>Principal Investigator</role>
    <affiliation>BP Koirala Institute of Health Sciences</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>BP Koirala Institute of Health Sciences</name>
      <address>
        <city>Dharān Bāzār</city>
        <state>One</state>
        <zip>7053</zip>
        <country>Nepal</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Nepal</country>
  </location_countries>
  <reference>
    <citation>Kilkenny M, Marks R. The descriptive epidemiology of warts in the community. Australas J Dermatol. 1996 May;37(2):80-6. doi: 10.1111/j.1440-0960.1996.tb01010.x.</citation>
    <PMID>8687332</PMID>
  </reference>
  <reference>
    <citation>Sterling JC, Gibbs S, Haque Hussain SS, Mohd Mustapa MF, Handfield-Jones SE. British Association of Dermatologists' guidelines for the management of cutaneous warts 2014. Br J Dermatol. 2014 Oct;171(4):696-712. doi: 10.1111/bjd.13310. Epub 2014 Oct 1. No abstract available.</citation>
    <PMID>25273231</PMID>
  </reference>
  <reference>
    <citation>Bruggink SC, Eekhof JA, Egberts PF, van Blijswijk SC, Assendelft WJ, Gussekloo J. Natural course of cutaneous warts among primary schoolchildren: a prospective cohort study. Ann Fam Med. 2013 Sep-Oct;11(5):437-41. doi: 10.1370/afm.1508.</citation>
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    <PMID>2271835</PMID>
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  <reference>
    <citation>Lipke MM. An armamentarium of wart treatments. Clin Med Res. 2006 Dec;4(4):273-93. doi: 10.3121/cmr.4.4.273.</citation>
    <PMID>17210977</PMID>
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  <reference>
    <citation>Leung L. Recalcitrant nongenital warts. Aust Fam Physician. 2011 Jan-Feb;40(1-2):40-2.</citation>
    <PMID>21301692</PMID>
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  <reference>
    <citation>Goihman-Yahr M, Goldblum OM. Immunotherapy and warts: a point of view. Clin Dermatol. 2008 Mar-Apr;26(2):223-5. doi: 10.1016/j.clindermatol.2007.10.011. No abstract available.</citation>
    <PMID>18472063</PMID>
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  <verification_date>April 2021</verification_date>
  <study_first_submitted>June 8, 2020</study_first_submitted>
  <study_first_submitted_qc>June 10, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <results_first_submitted>February 9, 2021</results_first_submitted>
  <results_first_submitted_qc>April 7, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">April 9, 2021</results_first_posted>
  <last_update_submitted>April 7, 2021</last_update_submitted>
  <last_update_submitted_qc>April 7, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 9, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>B.P. Koirala Institute of Health Sciences</investigator_affiliation>
    <investigator_full_name>Dr. Bibisha Baaniya</investigator_full_name>
    <investigator_title>Junior Resident</investigator_title>
  </responsible_party>
  <keyword>Warts</keyword>
  <keyword>Intralesional</keyword>
  <keyword>MMR</keyword>
  <keyword>Vitamin D</keyword>
  <keyword>Immunotherapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Warts</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vitamin D</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol, Statistical Analysis Plan, and Informed Consent Form</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>May 18, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/59/NCT04428359/Prot_SAP_ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Measles, Mumps, Rubella Vaccine</title>
          <description>All Group A patients will receive intralesional MMR.&#xD;
Measles-Mumps-Rubella Vaccine: Group A patients will receive intralesional injection of upto 0.5 mL of reconstituted MMR vaccine into a single or a maximum of 5 warts at a time in case of multiple warts. Intralesional injection will be given every three weeks for a maximum of 5 doses or until complete resolution, whichever is earlier.</description>
        </group>
        <group group_id="P2">
          <title>Vitamin D3</title>
          <description>All Group B patients will receive intralesional Vitamin D3&#xD;
Vit D: Group B patients will receive a maximum of 0.5 mL Inj. Vitamin D3 (600,000 IU; 15mg/ml) in each session after injection of IL lignocaine with 31 G insulin syringe. In cases of multiple warts, a maximum of 5 warts will be injected at a time. The session will be done at 3 weekly intervals for a maximum of 5 sessions or until complete resolution of warts, whichever is earlier</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="33"/>
                <participants group_id="P2" count="33"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="31"/>
                <participants group_id="P2" count="30"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Measles, Mumps, Rubella Vaccine</title>
          <description>All Group A patients will receive intralesional MMR.&#xD;
Measles-Mumps-Rubella Vaccine: Group A patients will receive intralesional injection of upto 0.5 mL of reconstituted MMR vaccine into a single or a maximum of 5 warts at a time in case of multiple warts. Intralesional injection will be given every three weeks for a maximum of 5 doses or until complete resolution, whichever is earlier.</description>
        </group>
        <group group_id="B2">
          <title>Vitamin D3</title>
          <description>All Group B patients will receive intralesional Vitamin D3&#xD;
Vit D: Group B patients will receive a maximum of 0.5 mL Inj. Vitamin D3 (600,000 IU; 15mg/ml) in each session after injection of IL lignocaine with 31 G insulin syringe. In cases of multiple warts, a maximum of 5 warts will be injected at a time. The session will be done at 3 weekly intervals for a maximum of 5 sessions or until complete resolution of warts, whichever is earlier</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="31"/>
            <count group_id="B2" value="30"/>
            <count group_id="B3" value="61"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="22.32" spread="11.167"/>
                    <measurement group_id="B2" value="23.93" spread="8.383"/>
                    <measurement group_id="B3" value="23.11" spread="9.847"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="30"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Brahmin/ Chhetri</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Madhesi</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Janajati</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="32"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Others</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Nepal</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                    <measurement group_id="B2" value="30"/>
                    <measurement group_id="B3" value="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>ITT population</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                    <measurement group_id="B2" value="30"/>
                    <measurement group_id="B3" value="61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Efficacy of IL MMR and IL Vitamin D3 in Treatment of Warts</title>
        <description>Percentage of patients showing complete response to IL MMR and IL Vitamin D3&#xD;
Complete response -Complete disappearance of warts including distant ones and skin texture at the site is restored to normal (100%) Excellent response- Reduction in size and number including distant ones and few residual warts still visible (75-99%) Good response- Some reduction in size only including that of distant ones but no decrease in number of warts (50-74%) Poor or no response- No significant change in size and number of warts (0-49%)</description>
        <time_frame>Starting of treatment to end of three months follow-up after completing treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Measles, Mumps, Rubella Vaccine</title>
            <description>All Group A patients will receive intralesional MMR.&#xD;
Measles-Mumps-Rubella Vaccine: Group A patients will receive intralesional injection of upto 0.5 mL of reconstituted MMR vaccine into a single or a maximum of 5 warts at a time in case of multiple warts. Intralesional injection will be given every three weeks for a maximum of 5 doses or until complete resolution, whichever is earlier.</description>
          </group>
          <group group_id="O2">
            <title>Vitamin D3</title>
            <description>All Group B patients will receive intralesional Vitamin D3&#xD;
Vit D: Group B patients will receive a maximum of 0.5 mL Inj. Vitamin D3 (600,000 IU; 15mg/ml) in each session after injection of IL lignocaine with 31 G insulin syringe. In cases of multiple warts, a maximum of 5 warts will be injected at a time. The session will be done at 3 weekly intervals for a maximum of 5 sessions or until complete resolution of warts, whichever is earlier</description>
          </group>
        </group_list>
        <measure>
          <title>Efficacy of IL MMR and IL Vitamin D3 in Treatment of Warts</title>
          <description>Percentage of patients showing complete response to IL MMR and IL Vitamin D3&#xD;
Complete response -Complete disappearance of warts including distant ones and skin texture at the site is restored to normal (100%) Excellent response- Reduction in size and number including distant ones and few residual warts still visible (75-99%) Good response- Some reduction in size only including that of distant ones but no decrease in number of warts (50-74%) Poor or no response- No significant change in size and number of warts (0-49%)</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="31"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Complete response</title>
                  <measurement_list>
                    <measurement group_id="O1" value="25"/>
                    <measurement group_id="O2" value="22"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Excellent response</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Good response</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Poor or no response</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants in Each Education Level Group</title>
        <description>Distribution of wart patients into different education level like professional degree, graduate, intermediate, high school, middle school, primary school or illiterate</description>
        <time_frame>At the time of enrollment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Measles, Mumps, Rubella Vaccine</title>
            <description>All Group A patients will receive intralesional MMR.&#xD;
Measles-Mumps-Rubella Vaccine: Group A patients will receive intralesional injection of upto 0.5 mL of reconstituted MMR vaccine into a single or a maximum of 5 warts at a time in case of multiple warts. Intralesional injection will be given every three weeks for a maximum of 5 doses or until complete resolution, whichever is earlier.</description>
          </group>
          <group group_id="O2">
            <title>Vitamin D3</title>
            <description>All Group B patients will receive intralesional Vitamin D3&#xD;
Vit D: Group B patients will receive a maximum of 0.5 mL Inj. Vitamin D3 (600,000 IU; 15mg/ml) in each session after injection of IL lignocaine with 31 G insulin syringe. In cases of multiple warts, a maximum of 5 warts will be injected at a time. The session will be done at 3 weekly intervals for a maximum of 5 sessions or until complete resolution of warts, whichever is earlier</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants in Each Education Level Group</title>
          <description>Distribution of wart patients into different education level like professional degree, graduate, intermediate, high school, middle school, primary school or illiterate</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="31"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Graduate and higher</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Intermediate</title>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>High School</title>
                  <measurement_list>
                    <measurement group_id="O1" value="16"/>
                    <measurement group_id="O2" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Middle School</title>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Primary and informal</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants in Each Occupation Group</title>
        <description>Number of participants with different occupations like professional, semiprofessional, clerical/shop/farm, skilled worker, semiskilled worker, unskilled worker, unemployed</description>
        <time_frame>At the time of enrollment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Measles, Mumps, Rubella Vaccine</title>
            <description>All Group A patients will receive intralesional MMR.&#xD;
Measles-Mumps-Rubella Vaccine: Group A patients will receive intralesional injection of upto 0.5 mL of reconstituted MMR vaccine into a single or a maximum of 5 warts at a time in case of multiple warts. Intralesional injection will be given every three weeks for a maximum of 5 doses or until complete resolution, whichever is earlier.</description>
          </group>
          <group group_id="O2">
            <title>Vitamin D3</title>
            <description>All Group B patients will receive intralesional Vitamin D3&#xD;
Vit D: Group B patients will receive a maximum of 0.5 mL Inj. Vitamin D3 (600,000 IU; 15mg/ml) in each session after injection of IL lignocaine with 31 G insulin syringe. In cases of multiple warts, a maximum of 5 warts will be injected at a time. The session will be done at 3 weekly intervals for a maximum of 5 sessions or until complete resolution of warts, whichever is earlier</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants in Each Occupation Group</title>
          <description>Number of participants with different occupations like professional, semiprofessional, clerical/shop/farm, skilled worker, semiskilled worker, unskilled worker, unemployed</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="31"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Semiprofessional</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Clerical/shop/farmer</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Semiskilled</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unskilled</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unemployed</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Student</title>
                  <measurement_list>
                    <measurement group_id="O1" value="18"/>
                    <measurement group_id="O2" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Homemaker</title>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration</title>
        <description>Duration of warts</description>
        <time_frame>At the time of enrollment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Measles, Mumps, Rubella Vaccine</title>
            <description>All Group A patients will receive intralesional MMR.&#xD;
Measles-Mumps-Rubella Vaccine: Group A patients will receive intralesional injection of upto 0.5 mL of reconstituted MMR vaccine into a single or a maximum of 5 warts at a time in case of multiple warts. Intralesional injection will be given every three weeks for a maximum of 5 doses or until complete resolution, whichever is earlier.</description>
          </group>
          <group group_id="O2">
            <title>Vitamin D3</title>
            <description>All Group B patients will receive intralesional Vitamin D3&#xD;
Vit D: Group B patients will receive a maximum of 0.5 mL Inj. Vitamin D3 (600,000 IU; 15mg/ml) in each session after injection of IL lignocaine with 31 G insulin syringe. In cases of multiple warts, a maximum of 5 warts will be injected at a time. The session will be done at 3 weekly intervals for a maximum of 5 sessions or until complete resolution of warts, whichever is earlier</description>
          </group>
        </group_list>
        <measure>
          <title>Duration</title>
          <description>Duration of warts</description>
          <units>months</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="31"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24.2977" spread="23.99027"/>
                    <measurement group_id="O2" value="26.2417" spread="24.28020"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Effect of the Warts on Patient's Life as Assessed by Dermatological Life Quality Index</title>
        <description>Quality of life (QoL) will be measured in wart patients, using the Nepali version of the dermatology life quality index (DLQI) questionnaire before initiation of treatment and at the end of follow up. DLQI contains 10 questions that involves 6 sections: symptoms and feelings, daily activities, leisure, work and school, personal relationships and treatment. Questions 1 and 2 assess symptoms and feelings; 3 and 4, daily activities; 5 and 6, leisure; 7, work and school; 8 and 9, personal relationships and 10, treatment.&#xD;
The DLQI consists of 10 questions. Each question is given 4 options from not at all effect (score 0) to very much effect (score 3). The minimum and maximum possible score, thus, is 0 and 30 respectively.&#xD;
Meaning of DLQI Scores 0-1 = no effect at all on patient's life 2-5 = small effect on patient's life 6-10 = moderate effect on patient's life 11-20 = very large effect on patient's life 21-30 = extremely large effect on patient's life&#xD;
.</description>
        <time_frame>At the time of enrollment and at the end of three months follow- up after completion of treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Measles, Mumps, Rubella Vaccine</title>
            <description>All Group A patients will receive intralesional MMR.&#xD;
Measles-Mumps-Rubella Vaccine: Group A patients will receive intralesional injection of upto 0.5 mL of reconstituted MMR vaccine into a single or a maximum of 5 warts at a time in case of multiple warts. Intralesional injection will be given every three weeks for a maximum of 5 doses or until complete resolution, whichever is earlier.</description>
          </group>
          <group group_id="O2">
            <title>Vitamin D3</title>
            <description>All Group B patients will receive intralesional Vitamin D3&#xD;
Vit D: Group B patients will receive a maximum of 0.5 mL Inj. Vitamin D3 (600,000 IU; 15mg/ml) in each session after injection of IL lignocaine with 31 G insulin syringe. In cases of multiple warts, a maximum of 5 warts will be injected at a time. The session will be done at 3 weekly intervals for a maximum of 5 sessions or until complete resolution of warts, whichever is earlier</description>
          </group>
        </group_list>
        <measure>
          <title>Effect of the Warts on Patient's Life as Assessed by Dermatological Life Quality Index</title>
          <description>Quality of life (QoL) will be measured in wart patients, using the Nepali version of the dermatology life quality index (DLQI) questionnaire before initiation of treatment and at the end of follow up. DLQI contains 10 questions that involves 6 sections: symptoms and feelings, daily activities, leisure, work and school, personal relationships and treatment. Questions 1 and 2 assess symptoms and feelings; 3 and 4, daily activities; 5 and 6, leisure; 7, work and school; 8 and 9, personal relationships and 10, treatment.&#xD;
The DLQI consists of 10 questions. Each question is given 4 options from not at all effect (score 0) to very much effect (score 3). The minimum and maximum possible score, thus, is 0 and 30 respectively.&#xD;
Meaning of DLQI Scores 0-1 = no effect at all on patient's life 2-5 = small effect on patient's life 6-10 = moderate effect on patient's life 11-20 = very large effect on patient's life 21-30 = extremely large effect on patient's life&#xD;
.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="31"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>no effect at all on patient's life</title>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>small effect on patient's life</title>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                    <measurement group_id="O2" value="17"/>
                  </measurement_list>
                </category>
                <category>
                  <title>moderate effect on patient's life</title>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>very large effect on patient's life</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>extremely large effect on patient's life</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Number of Warts</title>
        <description>Number of warts in patients</description>
        <time_frame>At the time of enrollment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Measles, Mumps, Rubella Vaccine</title>
            <description>All Group A patients will receive intralesional MMR.&#xD;
Measles-Mumps-Rubella Vaccine: Group A patients will receive intralesional injection of upto 0.5 mL of reconstituted MMR vaccine into a single or a maximum of 5 warts at a time in case of multiple warts. Intralesional injection will be given every three weeks for a maximum of 5 doses or until complete resolution, whichever is earlier.</description>
          </group>
          <group group_id="O2">
            <title>Vitamin D3</title>
            <description>All Group B patients will receive intralesional Vitamin D3&#xD;
Vit D: Group B patients will receive a maximum of 0.5 mL Inj. Vitamin D3 (600,000 IU; 15mg/ml) in each session after injection of IL lignocaine with 31 G insulin syringe. In cases of multiple warts, a maximum of 5 warts will be injected at a time. The session will be done at 3 weekly intervals for a maximum of 5 sessions or until complete resolution of warts, whichever is earlier</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Warts</title>
          <description>Number of warts in patients</description>
          <units>Warts</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="31"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21.58" spread="22.344"/>
                    <measurement group_id="O2" value="21" spread="31.107"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Size</title>
        <description>Size range of warts</description>
        <time_frame>At the time of enrollment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Measles, Mumps, Rubella Vaccine</title>
            <description>All Group A patients will receive intralesional MMR.&#xD;
Measles-Mumps-Rubella Vaccine: Group A patients will receive intralesional injection of upto 0.5 mL of reconstituted MMR vaccine into a single or a maximum of 5 warts at a time in case of multiple warts. Intralesional injection will be given every three weeks for a maximum of 5 doses or until complete resolution, whichever is earlier.</description>
          </group>
          <group group_id="O2">
            <title>Vitamin D3</title>
            <description>All Group B patients will receive intralesional Vitamin D3&#xD;
Vit D: Group B patients will receive a maximum of 0.5 mL Inj. Vitamin D3 (600,000 IU; 15mg/ml) in each session after injection of IL lignocaine with 31 G insulin syringe. In cases of multiple warts, a maximum of 5 warts will be injected at a time. The session will be done at 3 weekly intervals for a maximum of 5 sessions or until complete resolution of warts, whichever is earlier</description>
          </group>
        </group_list>
        <measure>
          <title>Size</title>
          <description>Size range of warts</description>
          <units>cm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="31"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.242" spread="0.9359"/>
                    <measurement group_id="O2" value="0.937" spread="0.5404"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Number of Participants With Each Progression Type</title>
        <description>Number of participants with different progressions of warts like Gradual or rapid or stable or regressing lesions</description>
        <time_frame>At the time of enrollment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Measles, Mumps, Rubella Vaccine</title>
            <description>All Group A patients will receive intralesional MMR.&#xD;
Measles-Mumps-Rubella Vaccine: Group A patients will receive intralesional injection of upto 0.5 mL of reconstituted MMR vaccine into a single or a maximum of 5 warts at a time in case of multiple warts. Intralesional injection will be given every three weeks for a maximum of 5 doses or until complete resolution, whichever is earlier.</description>
          </group>
          <group group_id="O2">
            <title>Vitamin D3</title>
            <description>All Group B patients will receive intralesional Vitamin D3&#xD;
Vit D: Group B patients will receive a maximum of 0.5 mL Inj. Vitamin D3 (600,000 IU; 15mg/ml) in each session after injection of IL lignocaine with 31 G insulin syringe. In cases of multiple warts, a maximum of 5 warts will be injected at a time. The session will be done at 3 weekly intervals for a maximum of 5 sessions or until complete resolution of warts, whichever is earlier</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Each Progression Type</title>
          <description>Number of participants with different progressions of warts like Gradual or rapid or stable or regressing lesions</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="31"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Gradual</title>
                  <measurement_list>
                    <measurement group_id="O1" value="23"/>
                    <measurement group_id="O2" value="27"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Rapid</title>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Number of Participants Who Had Taken Past Treatment</title>
        <description>Frequency of different types of past treatment taken- either traditional or medical treatments</description>
        <time_frame>At the time of enrollment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Measles, Mumps, Rubella Vaccine</title>
            <description>All Group A patients will receive intralesional MMR.&#xD;
Measles-Mumps-Rubella Vaccine: Group A patients will receive intralesional injection of upto 0.5 mL of reconstituted MMR vaccine into a single or a maximum of 5 warts at a time in case of multiple warts. Intralesional injection will be given every three weeks for a maximum of 5 doses or until complete resolution, whichever is earlier.</description>
          </group>
          <group group_id="O2">
            <title>Vitamin D3</title>
            <description>All Group B patients will receive intralesional Vitamin D3&#xD;
Vit D: Group B patients will receive a maximum of 0.5 mL Inj. Vitamin D3 (600,000 IU; 15mg/ml) in each session after injection of IL lignocaine with 31 G insulin syringe. In cases of multiple warts, a maximum of 5 warts will be injected at a time. The session will be done at 3 weekly intervals for a maximum of 5 sessions or until complete resolution of warts, whichever is earlier</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Had Taken Past Treatment</title>
          <description>Frequency of different types of past treatment taken- either traditional or medical treatments</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="31"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>None</title>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                    <measurement group_id="O2" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Traditional</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Medical</title>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>6 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Measles, Mumps, Rubella Vaccine</title>
          <description>All Group A patients will receive intralesional MMR.&#xD;
Measles-Mumps-Rubella Vaccine: Group A patients will receive intralesional injection of upto 0.5 mL of reconstituted MMR vaccine into a single or a maximum of 5 warts at a time in case of multiple warts. Intralesional injection will be given every three weeks for a maximum of 5 doses or until complete resolution, whichever is earlier.</description>
        </group>
        <group group_id="E2">
          <title>Vitamin D3</title>
          <description>All Group B patients will receive intralesional Vitamin D3&#xD;
Vit D: Group B patients will receive a maximum of 0.5 mL Inj. Vitamin D3 (600,000 IU; 15mg/ml) in each session after injection of IL lignocaine with 31 G insulin syringe. In cases of multiple warts, a maximum of 5 warts will be injected at a time. The session will be done at 3 weekly intervals for a maximum of 5 sessions or until complete resolution of warts, whichever is earlier</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Hypervitaminosis D</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="31" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="30" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="31" subjects_affected="31" subjects_at_risk="31"/>
                <counts group_id="E2" events="30" subjects_affected="30" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Swelling</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" events="18" subjects_affected="18" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hyperpigmentation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="31"/>
                <counts group_id="E2" events="9" subjects_affected="9" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypopigmentation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Bibisha Baaniya</name_or_title>
      <organization>BP Koirala Institute of Health Sciences</organization>
      <phone>9841744777 ext +977</phone>
      <email>cul.bibisha@gmail.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT04428359
org study id: IRC/1607/019
secondary id: 858 - 2019
nct id: NCT04428359
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Common warts are papulonodular epidermal lesions caused by human papillomavirus (HPV) usually
      by the strains 1, 2, 4, 27 or 57. Cutaneous warts occur in 7% to 10% of the general
      population, with a maximum incidence between 12 and 16 years. There are multiple destructive
      treatment modalities of wart but they have many adverse effects. Hence immunotherapy is
      becoming popular in treatment of warts. It is believed that the injection to the HPV-infected
      tissue induces a strong nonspecific pro-inflammatory signal and attracts the
      antigen-presenting cells. Which then promotes a Th1 cytokine response and leads to
      delayed-type hypersensitivity reaction leading to the eradication of the HPV-infected cells.

      We are undertaking a study to evaluate and compare the safety and efficacy of 2 such
      immunotherapeutic agents namely, IL measles, mumps and rubella (MMR) vaccine versus IL
      vitamin D3 for the treatment of warts.

      RESEARCH HYPOTHESIS Null Hypotheses: IL MMR vaccine is not better than IL Vitamin D in the
      treatment of wart Alternative hypothesis: IL MMR vaccine is better than IL Vitamin D in the
      treatment of wart

      Method: A total of 60 patients will be included in the study, 30 in each group. Group A and
      Group B patients will be injected with 0.5 ml of IL MMR and 0.5 ml of IL vitamin D3
      respectively into a single or a maximum of 5 warts at a time in case of multiple warts. The
      IL injection will be given every 3 weeks for a maximum of 5 doses. Clinical assessment will
      be done by taking photographs and measurements at baseline, before each treatment session,
      and 3 months after the completion of treatment. The response will be evaluated by a decrease
      in the size and number of the wart(s) and photographic comparison. The response will be
      considered complete if there is a complete clearance of the wart(s), good if the wart(s) will
      regress in size by 75-99%, moderate if they regress by 50-74% and no or mild if there will be
      a 0-49% decrease in wart(s). Immediate and late side effects of MMR and Vitamin D will be
      evaluated after each session. Follow up will be made monthly for 3 months to detect any
      recurrence. Quality of life (QoL) will be measured in wart patients, using the Nepali version
      of the dermatology life quality index (DLQI) questionnaire before initiation of treatment and
      at the end of follow up.

      Statistical analysis will be done using Statistical Package for the Social Sciences 10.5
      version.
INTRODUCTION Warts are common skin conditions resulting from infection of keratinocytes by
      human papillomavirus (HPV). After infection of the basal layer, there is clonal proliferation
      leading to epidermal thickening and hyperkeratinization and eventually results in a visible
      wart. HPVs are ubiquitous, epitheliotropic non-enveloped small double-stranded DNA viruses.
      Over 150 types of HPVs have been identified. Among them verruca vulgaris are usually caused
      by HPV types 1, 2, 4, 27 or 57, and plane warts by HPV types 3 or 10.

      Cutaneous warts occur in 7% to 10% of the general population, with a maximum incidence
      between the ages of 12 and 16 years. In children, clearance can occur after only a few
      months, with 50% at 1 year and about 65%-78% by 2 years. The rate of clearance is influenced
      by factors like virus strain, host immune status, extent and duration of warts. The
      transmission of warts occurs from direct contact or indirectly via fomites.

      There are multiple destructive, antiproliferative and antiviral agents in treatment of warts.
      Other modalities include hypnotherapy, acupuncture, local hyperthermia, therapeutic
      vaccination and combinations of the previous agents. Destructive therapies usually come with
      many adverse effects hence immunotherapy is becoming more popular, especially in the
      treatment of refractory cutaneous and genital warts. These include various topical,
      intralesional (IL) and systemic agents. IL Measles, Mumps, rubella (MMR) and IL vitamin D3
      are examples of immunotherapeutic agents.

      Immunotherapy is defined as a type of biological therapy that uses substances to stimulate or
      suppress the immune system to help the body fight cancer, infection, and other diseases.
      Immunotherapy can affect the immune system in general or can be cell-specific.

      Immunotherapy is believed to induce a strong nonspecific pro-inflammatory signal and attract
      the antigen-presenting cells. This is associated with the release of cytokines such as IL-2,
      IL-8, IL-12, IL-I8, tumor necrosis factor-α, and interferon-γ. This then promotes a Th1
      cytokine response which leads to the activation of delayed-type hypersensitivity reaction
      leading to the eradication of the HPV-infected cells. Furthermore, the trauma of the
      injection may also cause a resolution in previously sensitized individuals. Vitamin D3 is
      also claimed to regulate epidermal cell differentiation and proliferation and may modulate
      cytokine production through its action upon vitamin D receptors (VDRs). Since IL antigen
      immunotherapy enhances recognition of the virus by the immune system it causes clearance of
      both treated and untreated lesions and helps to prevent future clinical infection through
      induction of long-term acquired immunity to HPV.

      MMR vaccine is included in immunization schedule of Nepal so pre-sensitization skin test is
      not needed as all patients are expected to be immune. The presence of 3 different antigens in
      MMR increases the sensitivity to the injected antigen and decreases the likelihood of anergy.
      Side effects of MMR include pain during injection, flu-like symptoms, pruritus and burning
      sensation.

      IL vitamin D is a novel addition to therapies in warts as it is a simple, effective,
      well-tolerable, and inexpensive method with negligible local and systemic side effects. Side
      effects of Vitamin D3 include transient mild to moderate pain, edema at the site of injection
      and mild erythema. Additionally, it would be safer to monitor serum vitamin D and calcium
      levels before and after intralesional vitamin D treatment to prevent possible
      hypervitaminosis D.

      RATIONALE Intralesional Immunotherapy is an emerging method of treatment of wart in which
      injection in a single wart causes the resolution of distant warts as well. Compared to other
      destructive modalities, it is more effective and comfortable for the patient as it obviates
      the need for individual treatment of each wart. In addition it has a lower rate of
      recurrence, avoids adverse effects such as scarring, is more cost-effective in multiple warts
      and decreases the time a physician has to spend on each patient. Further both injection MMR
      and Vitamin D3 are readily available as compared to other immunotherapeutic agents like
      purified protein derivative and candida antigen.

      IL MMR vaccine has been used for a longer time than IL vitamin D and there are more
      comparative studies showing efficacy of MMR vaccine with rates of clearance ranging from
      70.4% to 82.4%. The clearance rates for IL vitamin D ranges from 40% to 90%.

      The advantages of vitamin D over MMR vaccine are cost-effectiveness, non-requirement of
      maintenance of cold chain, easy availability, and feasibility of use in immunosuppressed
      patients.

      As per Institute of Medicine (IOM), the tolerable upper intake of vitamin D is 4000 IU/day
      for anyone older than 9 years such that annual maximum dose will be 1,460,000 IU. The total
      amount of vitamin D that we will be administering will be 1,500,000 IU. Furthermore, since we
      are giving it intralesionally systemic absorption is likely to be low although data on exact
      amount of IL vitamin D that gets absorbed systemically is not available. In other studies,
      patients have been evaluated clinically for signs and symptoms of hypervitaminosis D however,
      no signs of toxicity were observed.

      As per our literature search,

        1. No previous studies on immunotherapy in wart have been conducted in our country

        2. No comparative studies have been done to compare IL MMR and IL vitamin D3 in treatment
           of wart hence we aim to establish efficacy of each and compare the two.

      OBJECTIVES

      Primary Objectives:

        1. To determine the efficacy of IL MMR vaccine in the treatment of Wart

        2. To determine the efficacy of IL vitamin D in the treatment of wart

        3. To compare the efficacy of IL MMR vaccine and IL Vitamin D

      Secondary Objective:

        1. To determine the clinical and demographic profile of patients with different types of
           warts visiting Dermatology outpatient department(OPD) of BP Koirala Institute of Health
           Sciences (BPKIHS)

        2. To determine the side effects of IL MMR vaccine and IL Vitamin D in treatment of wart

        3. To determine Dermatology life quality index (DLQI) in wart patients.

      Operational definition Wart - clinical diagnosis made by a dermatologist Complete response
      (100%)- Complete disappearance of warts including distant ones and skin texture at the site
      is restored to normal Excellent response (75-99%)-Reduction in size and number including
      distant ones and few residual warts still visible Good response (50-74%)-Some reduction in
      size only including that of distant ones but no decrease in number of warts Poor or no
      response (0-49%)-No significant change in size and number of warts Recurrence- Recurrence
      during the study period

      MATERIALS AND METHODOLOGY Materials: Study population will be all patients clinically
      diagnosed with warts visiting the Dermatology OPD of BPKIHS, Dharan.

      Study design: Prospective comparative longitudinal study Study Period: Probable duration of
      the study will be 1 year after approval from the Institutional Review Committee (IRC) and
      Nepal Health Research Council (NHRC) Ethical Clearance: Taken from IRC, BPKIHS and NHRC
      Conflict of interest: None Sampling Technique: Census method with all consecutive patients
      meeting inclusion criteria for initial 6 months Sample size The study considers a 95%
      confidence interval, 80% power to estimate sample size. According to the literature review,
      it was found that there was 84.6% and 40% improvement in MMR and Vitamin D respectively.

      Now using the sample size estimation formula for 2 proportion {(Zα√2p(1-p)+ Z1-β√((p1(1-p1)
      p2(1-p2)}2))/(p1-p2)2 Where n= sample size for each group p1 = 0.846 p2 = 0.40 p= (p1 +p2)/2
      Zα=1.96 Z1-β = 1.28 Using above formula, n= 12.3 The formula for actual sample size is
      n/4{1+√(1+4/n|p1-p2|)}2 na = 16.48 Adding 10% in calculated value to reduce bias sampling
      technique, the minimum sample size in each group is 18.13 =19 Considering loss of follow up,
      sample size in each group= 30 Total sample size= 60

      Methodology Based on the computer generated random number table, patients satisfying
      inclusion criteria will be assigned to either Group A or Group B once they come to OPD.
      Informed consent will be taken and detailed information including personal data, past
      history, medical history, drug history, clinical data like site, size, number and
      distribution of lesions will be recorded in preset pro forma. Photographs of the lesions will
      be taken before the first treatment session, in every treatment session and 3 months after
      last session.

      Group A Freeze-dried MMR vaccine single-use vials stored at 2°C-8°C will be reconstituted
      with 0.5 mL of distilled water immediately before IL use. If reconstituted vaccine is not
      used within 8 hours it must be discarded. All Group A patients will receive IL injection of
      upto 0.5 mL of reconstituted MMR vaccine into a single or a maximum of 5 warts at a time in
      case of multiple warts with 31 G insulin syringe with beveled edge facing upward. Amount of
      injection on each wart will depend on the size of each wart. The injection will be given
      every three weeks for a maximum of 5 doses.

      Group B All Group B patients will receive a maximum of 0.5 mL Inj. Vitamin D3 (600,000 IU;
      15mg/ml) in each session after injection of IL lignocaine with 31 G insulin syringe. In cases
      of multiple warts, a maximum of 5 warts will be injected at a time. Amount of injection on
      each wart will depend on the size of each wart. The session will be done at 3 weekly
      intervals for a maximum of 5 sessions or until complete resolution of warts, whichever is
      earlier. In patients of group B serum vitamin D level will be measured after 20 days of 3rd
      dose and 1 month after the last dose to ensure safe monitoring.

      Patient and physician global assessment using 'Visual Analog Scale score' and photographic
      comparison will be used to assess the response to treatment as mentioned in operational
      definition. Immediate and late adverse effects in both groups will be evaluated after each
      treatment session. Necessary investigations and intervention will be done if needed. Follow
      up will be made monthly for 3 months to detect any recurrence.

      Quality of Life(QoL) QoL will be measured in wart patients, using the Nepali version of the
      dermatology life quality index (DLQI) questionnaire before initiation of treatment and at the
      end of follow up. DLQI contains 10 questions that involves 6 sections: symptoms and feelings,
      daily activities, leisure, work and school, personal relationships and treatment. Questions 1
      and 2 assess symptoms and feelings; 3 and 4, daily activities; 5 and 6, leisure; 7, work and
      school; 8 and 9, personal relationships and 10, treatment. The clinically meaningful change
      or reduction in the DLQI score is measured as the change in score from one band to the other.

      Statistical analysis

        1. Data handling: Data will be entered in Microsoft Excel 2010 and statistical analysis
           will be done using Statistical Package for the Social Sciences 10.5 version

        2. Coding: Alpha numerical code will be used

        3. Monitoring: Data will be entered after every day of work and supervised by guide.

        4. Statistical Analysis:

             1. Chi square test to compare the categorical data between the groups.

             2. Paired t test for comparing normally distributed continuous variables at different
                time point within the group

             3. Independent 't' test for comparing normally distributed continuous variables at
                different time point between the groups

             4. Wilcoxon signed rank test to compare the not normally distributed variables,
                ordinal data

             5. Mann- Whitney U test to compare the not normally distributed variables, ordinal
                data.

             6. Kaplan-Meier curves to compare the response rate on each follow up visit between
                the groups.

      Test of significance will be considered when value of p ≤ 0.05.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Group A - will receive IL MMR Group B- will receive IL Vitamin D3
primary purpose: Treatment
masking: Single (Participant)
masking description: Only patients will be blinded to the randomization and intervention.
measure: Efficacy of IL MMR and IL Vitamin D3 in Treatment of Warts
time frame: Starting of treatment to end of three months follow-up after completing treatment
description: Percentage of patients showing complete response to IL MMR and IL Vitamin D3
Complete response -Complete disappearance of warts including distant ones and skin texture at the site is restored to normal (100%) Excellent response- Reduction in size and number including distant ones and few residual warts still visible (75-99%) Good response- Some reduction in size only including that of distant ones but no decrease in number of warts (50-74%) Poor or no response- No significant change in size and number of warts (0-49%)
measure: Number of Participants in Each Education Level Group
time frame: At the time of enrollment
description: Distribution of wart patients into different education level like professional degree, graduate, intermediate, high school, middle school, primary school or illiterate
measure: Number of Participants in Each Occupation Group
time frame: At the time of enrollment
description: Number of participants with different occupations like professional, semiprofessional, clerical/shop/farm, skilled worker, semiskilled worker, unskilled worker, unemployed
measure: Duration
time frame: At the time of enrollment
description: Duration of warts
measure: Effect of the Warts on Patient's Life as Assessed by Dermatological Life Quality Index
time frame: At the time of enrollment and at the end of three months follow- up after completion of treatment
description: Quality of life (QoL) will be measured in wart patients, using the Nepali version of the dermatology life quality index (DLQI) questionnaire before initiation of treatment and at the end of follow up. DLQI contains 10 questions that involves 6 sections: symptoms and feelings, daily activities, leisure, work and school, personal relationships and treatment. Questions 1 and 2 assess symptoms and feelings; 3 and 4, daily activities; 5 and 6, leisure; 7, work and school; 8 and 9, personal relationships and 10, treatment.
The DLQI consists of 10 questions. Each question is given 4 options from not at all effect (score 0) to very much effect (score 3). The minimum and maximum possible score, thus, is 0 and 30 respectively.
Meaning of DLQI Scores 0-1 = no effect at all on patient's life 2-5 = small effect on patient's life 6-10 = moderate effect on patient's life 11-20 = very large effect on patient's life 21-30 = extremely large effect on patient's life
.
measure: Number of Warts
time frame: At the time of enrollment
description: Number of warts in patients
measure: Size
time frame: At the time of enrollment
description: Size range of warts
measure: Number of Participants With Each Progression Type
time frame: At the time of enrollment
description: Number of participants with different progressions of warts like Gradual or rapid or stable or regressing lesions
measure: Number of Participants Who Had Taken Past Treatment
time frame: At the time of enrollment
description: Frequency of different types of past treatment taken- either traditional or medical treatments
arm group label: Measles, Mumps, Rubella vaccine
arm group type: Experimental
description: All Group A patients will receive intralesional MMR.
arm group label: Vitamin D3
arm group type: Experimental
description: All Group B patients will receive intralesional Vitamin D3
intervention type: Drug
intervention name: Measles-Mumps-Rubella Vaccine
description: Group A patients will receive intralesional injection of upto 0.5 mL of reconstituted MMR vaccine into a single or a maximum of 5 warts at a time in case of multiple warts. Intralesional injection will be given every three weeks for a maximum of 5 doses or until complete resolution, whichever is earlier.
arm group label: Measles, Mumps, Rubella vaccine
other name: MMR
intervention type: Drug
intervention name: Vit D
description: Group B patients will receive a maximum of 0.5 mL Inj. Vitamin D3 (600,000 IU; 15mg/ml) in each session after injection of IL lignocaine with 31 G insulin syringe. In cases of multiple warts, a maximum of 5 warts will be injected at a time. The session will be done at 3 weekly intervals for a maximum of 5 sessions or until complete resolution of warts, whichever is earlier
arm group label: Vitamin D3
other name: Vitamin D3
criteria: 
gender: All
minimum age: 12 Years
maximum age: N/A
healthy volunteers: No
last name: Bibisha Baaniya, MBBS
role: Principal Investigator
affiliation: BP Koirala Institute of Health Sciences
facility: 
country: Nepal
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citation: Chauhan PS, Mahajan VK, Mehta KS, Rawat R, Sharma V. The Efficacy and Safety of Intralesional Immunotherapy with Measles, Mumps, Rubella Virus Vaccine for the Treatment of Common Warts in Adults. Indian Dermatol Online J. 2019 Jan-Feb;10(1):19-26. doi: 10.4103/idoj.IDOJ_142_18.
PMID: 30775294
citation: El-Taweel AE, Salem RM, Allam AH. Cigarette smoking reduces the efficacy of intralesional vitamin D in the treatment of warts. Dermatol Ther. 2019 Mar;32(2):e12816. doi: 10.1111/dth.12816. Epub 2019 Jan 24.
PMID: 30623542
citation: Kavya M, Shashikumar BM, Harish MR, Shweta BP. Safety and Efficacy of Intralesional Vitamin D3 in Cutaneous Warts: An Open Uncontrolled Trial. J Cutan Aesthet Surg. 2017 Apr-Jun;10(2):90-94. doi: 10.4103/JCAS.JCAS_82_16.
PMID: 28852295
citation: Naseem R, Aamir S. The efficacy of intralesional measles, mumps, rubella (MMR) antigen in treatment of common warts. Pakistan J Med Heal Sci. 2013;7(4):1130-1133.
citation: Sobhy Mohamad N, Badran F, Yakout E. Evaluation of the efficacy of a combination - measles, mumps and rubella vaccine in the treatment of plantar warts. Our Dermatology Online. 2013;4(4):463-467. doi:10.7241/ourd.20134.118
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citation: Raju J, Swamy AV, Swamy BLN RK. Intralesional Measles, Mumps and Rubella (Mmr) Vaccine - an Effective Therapeutic Tool in the Treatment of Wart. J Evid Based Med Healthc. 2016;2(50):8548-8551. doi:10.18410/jebmh/2015/1176
citation: Rohit V, Gajula N. Role of Intralesional Measles Mumps Rubella Vaccine in Cutaneous Warts : A Case Control Study. 2017;(December):57-60.
responsible party type: Principal Investigator
investigator affiliation: B.P. Koirala Institute of Health Sciences
investigator full name: Dr. Bibisha Baaniya
investigator title: Junior Resident
mesh term: Warts
mesh term: Vitamin D
sharing ipd: No
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