<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/NCT03237533</url>
  </required_header>
  <id_info>
    <org_study_id>123456789</org_study_id>
    <nct_id>NCT03237533</nct_id>
  </id_info>
  <brief_title>Treatment Modalities of Oral Lichen Planus</brief_title>
  <acronym>OLP</acronym>
  <official_title>Comparative Efficacy of Dexamethasone, Doxycycline, Nystatin and Promethazine With Triamcinolone in Orabase as Symptomatic Treatment of Oral Lichen Planus, A Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Faisalabad</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Faisalabad</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>
      Background: Oral lichen planus (OLP) is a chronic inflammatory mucocutaneous autoimmune&#xD;
      disease mainly affecting stratum basal of the epithelium. It is very painful and hamper the&#xD;
      daily routine of patients e.g. (talking, drinking, eating, maintaining normal relationships).&#xD;
      Different topical treatments have been tried for the symptomatic relief of OLP which include&#xD;
      topical corticosteroids (TCSs), topical calcineurin inhibitors (TCIs) retinoids,&#xD;
      photochemotherapy; amitryptaline; thalidomide; amlexanox and traditional medicines such as&#xD;
      curcumin, selenium-ACE combined with itraconazole, glycyrrhiza glabra and aloe vera. But the&#xD;
      exact treatment is still unknown.&#xD;
&#xD;
      Objective: To compare the efficacy of Dexamethasone, Doxycycline, Nystatin and Promethazine&#xD;
      cocktail with Triamcinolone as topical treatment of OLP Subjects and Methods: 40 patients of&#xD;
      symptomatic OLP will be randomly divided in to study and control group. Study group will be&#xD;
      given a cocktail containing dexamethasone, doxycycline, nystatin and promethazine and will be&#xD;
      advised to rinse with 1 and half teaspoon of this cocktail 3 times a day for 2 minutes for&#xD;
      the period of 8 weeks. Study group is also advised to apply an orabase containing 0.1%&#xD;
      triamcinolone on lesions 3 times a day for the period of 8 weeks. The control group will be&#xD;
      advised to apply only triamcinolone orabase 3 times a day for 8 weeks.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Introduction Oral lichen planus (OLP) is a chronic inflammatory mucocutaneous autoimmune&#xD;
      disease mainly affecting stratum basal of the epithelium. It is T-cell mediated immunological&#xD;
      disease that mostly occurs bilaterally on buccal mucosa while tongue and gingiva are other&#xD;
      commonly involved sites while palatal mucosa and floor of the mouth are rarely affected&#xD;
      (Roopashree MR, 2010, Torrente-Castells et al., 2010, Alves et al, 2010). The prevalence of&#xD;
      OLP in general population is 0.1-4% (Sugerman et al., 2002) mainly affecting the middle-aged&#xD;
      and elderly people (Ingafou et al., 2006) and female: male ratio 2:1 (Shen et al., 2012).&#xD;
&#xD;
      It has six clinical forms: keratotic, reticular, papular, plaquelike white patches, erosive,&#xD;
      atrophic, and bullous (Shen et al., 2012). Reticular and erosive form are most common (Alves&#xD;
      et al, 2010). Keratotic reticular, papular, plaque like white patches often present with no&#xD;
      complaints (Oczko et al, 2011), while erosive, atrophic, and ulcerative lesions are a painful&#xD;
      or present with a burning sensation, and thus make eating, speaking, and swallowing difficult&#xD;
      (Thongprasom et al., 2007). Histologically, a subepithelial infiltration in the form of dense&#xD;
      band of lymphocytes, increased numbers of intraepithelial lymphocytes and the liquefaction&#xD;
      degeneration of basal keratinocytes is seen in OLP (Payeras et al., 2013).&#xD;
&#xD;
      Several predisposing factors have been identified which may cause or progress OLP which&#xD;
      include immunity, infection, genetics, stress and endocrine. Recent researches showed an&#xD;
      increased activity of prolidase and oxidative stress in OLP patients, causing disturbance in&#xD;
      the antioxidant defense system (Batu et al, 2016, Ergun et al, 2011). Although the exact&#xD;
      cause is still not clear, facts show that an immunological process is involved in OLP which&#xD;
      is activated by an unknown antigen that change the basal keratinocytes of the oral mucosa and&#xD;
      these alterations cause the cell immune response to attack the keratinocytes. (Ismail et al.,&#xD;
      2007, Payeras et al., 2013). This antigen may be intrinsic or extrinsic, or both. Evidence&#xD;
      shows that bacteria can be one of the etiologic factors of OLP. An association has already&#xD;
      been found between OLP and infection, such as Ebstein Barr virus, Hepatitis C virus,&#xD;
      Helicobacter pylori and Candida Albicans. A study also pointed out the allergy to various&#xD;
      antigens coming in direct contact with oral cavity to contribute to the etiology of OLP. (D.&#xD;
      Wray, 2000) As the etiology is not known therefore there is no definitive treatment for OLP&#xD;
      and the mainstay of therapy for improving the life of these patients is symptomatic topical&#xD;
      treatment. Topical treatments which have been tried for the symptomatic OLP include topical&#xD;
      corticosteroids (TCSs), including betamethasone, clobetasol, dexamethasone and triamcinolone;&#xD;
      topical calcineurin inhibitors (TCIs) such as pimecrolimus, tacrolimus or ciclosporin;&#xD;
      retinoids such as tretinoin; photochemotherapy; amitryptaline; thalidomide; amlexanox and&#xD;
      traditional medicines such as curcumin, selenium-ACE combined with itraconazole, glycyrrhiza&#xD;
      glabra and aloe vera.&#xD;
&#xD;
      In a study both tacrolimus 0.1% ointment and pimecrolimus 1% cream were found equally&#xD;
      effective for the treatment of OLP (Vohra et al., 2016). Similarly another study showed that&#xD;
      Clobetasol propionate (0.05%) was found more effective than triamcinolone acetonate (0.1%)&#xD;
      and tacrolimus orabase (0.03%) for the management of OLP. This study also found that&#xD;
      triamcinolone 0.1% is superior to tacrolimus 0.03% in terms of effectiveness for the&#xD;
      treatment of OLP.(Sivaraman et al., 2016) According to another study both triamcinolone and&#xD;
      curcumin paste were found almost equally effective in reducing the pain and improving the&#xD;
      appearance of OLP lesions (Kia et al., 2015). In another study it was concluded that&#xD;
      combination of Selenium-ACE, corticosteroid and antifungal is a better treatment regimen for&#xD;
      the treatment of erosive ulcerative OLP than a capsule of 100 mg Itraconazole plus&#xD;
      dexamethsone mouthwash or dexamethasone alone (Belal, 2015). In another similar study&#xD;
      cocktail of clobetasol, ketoconazole and amitryptiline was found more efficacious than&#xD;
      diluted dexamethasone, nystatin and Diphenhydramine elixir (Javadzadeh et al, 2008). In a&#xD;
      comparative study tacrolimus 0.1% cream was found more effective than 0.05% clobetasol&#xD;
      propionate cream in reducing pain and healing of OLP lesions (Hettiarachchi et al., 2016).&#xD;
      Both thalidomide and dexamethasone were found almost equally effective in another trail (Wu&#xD;
      et al., 2010). In a trail of comperison between amlexanox paste and dexamethasone paste both&#xD;
      were found equally effective at the end of 7 days in terms of reduction in clinical signs&#xD;
      (erosion) and symptoms like pain and burning sensation (Fu et al., 2012). Some herbal&#xD;
      medicines have also been tried like Glycyrrhiza glabra and Aloe vera, in a trail to compare&#xD;
      the efficacy of 1% Glycyrrhiza glabra In orabase with 0.1% Triamcinolone Acetonide both were&#xD;
      found almost equally effective in reducing the pain and improving the appearance of OLP&#xD;
      lesions (Najafi et al., 2016) and in another trail both Aloe Vera Mouthwash and Triamcinolone&#xD;
      Acetonide were found almost equally effective in reducing the pain and in reducing the size&#xD;
      of OLP lesions (Mansourian et al., 2011) So steroids remained the mainstay of treatment for&#xD;
      OLP but evidence points towards the involvement of bacterial and fungal infections in the&#xD;
      pathogenesis of OLP as according to a recent study disbiosis was found in the buccal surface&#xD;
      mucosa of patients of OLP, as certain bacterial species were found in greater no in buccal&#xD;
      mucosa of OLP patients so they concluded that an association exists between bacterial&#xD;
      disbiosis of buccal mucosa and OLP (He et al., 2017). Similar studies showed that antibiotics&#xD;
      relieved symptoms of OLP effectively (Backman &amp; Jontell, 2007; Carbone et al, 1999). OLP is a&#xD;
      disease which reduces the individual's resistance and changes the candida albican's role from&#xD;
      commensalism to parasitism which is among the normal flora of oral cavity or candida may&#xD;
      secondarily infect the OLP lesions and exacerbate the signs and symptoms (santosh gowdru&#xD;
      shivanandappa, 2012). In a study 62% of OLP patients were found allergic to different&#xD;
      allergens which come in contact with mucosa in daily life so they found that association&#xD;
      exists between OLP and allergy (D. Wray, 2000). According to another study mast cell&#xD;
      hyperplasia was seen in OLP patients which suggests their role in pathogenesis of OLP (Ankle&#xD;
      R et al, 2007) The most used therapy is TCSs however its effectiveness is limited due to&#xD;
      opportunistic oral infections in patients with OLP. Adjunct antibiotic therapies have been&#xD;
      used to aid in symptomatic relief and improved response has been observed as compared to TCSs&#xD;
      alone. however none of the combined therapies have used antifungal as an additive in their&#xD;
      local applications, as candida is one of the opportunistic organisms that colonizes affected&#xD;
      sites. Role of allergy mechanisms have also been discussed.&#xD;
&#xD;
      Rationale Evidence of involvement of bacterial and fungal infections and allergy in the&#xD;
      pathogenesis of OLP suggests the need for the use of antibiotic, anti fungal and&#xD;
      antihistamine for the topical treatment of OLP and there is a gap in literature. That's why&#xD;
      current trail is being done to evaluate the efficacy of topical doxycycline, nyastatin and&#xD;
      promethazine along with dexamethasone for the symptomatic relief of OLP.&#xD;
&#xD;
      Hypothesis Dexamethasone, Doxycycline, Nystatin and Promethazine combination topical rinse&#xD;
      are more effective for the treatment of OLP than Triamcinolone alone Objective To compare the&#xD;
      efficacy of Dexamethasone, Doxycycline, Nystatin and Promethazine combination topical rinse&#xD;
      with Triamcinolone rinse as topical treatment of Oral Lichen Planus.&#xD;
&#xD;
      Operational Definitions • Oral Lichen Planus: Oral lichen planus (OLP) is a chronic&#xD;
      inflammatory mucocutaneous autoimmune disease mainly affecting stratum basal of the&#xD;
      epithelium.&#xD;
&#xD;
      Subjects and Methods Study Type Randomized control trail (Parallel arm study). Study Setting&#xD;
      Department of Oral Medicine &amp; Diagnosis and Department of Dermatology. Madina Teaching&#xD;
      Hospital Faisalabad.&#xD;
&#xD;
      Duration The study will be completed in 3 months after the approval of synopsis. Study&#xD;
      Population Patients of oral lichen planus visiting Department of Oral Medicine &amp; Diagnosis&#xD;
      and Department of Dermatology. Madina Teaching Hospital Faisalabad.&#xD;
&#xD;
      Sampling Technique Purposive Sampling, (Inclusion/exclusion criteria based)&#xD;
&#xD;
      Sample Selection Inclusion Criteria&#xD;
&#xD;
        1. Histopathologically proven patients of OLP of all age groups complaining of symptoms&#xD;
           such as pain, burning sensitivity to hot and spicy food.&#xD;
&#xD;
        2. Who have signed informed consent. Exclusion Criteria&#xD;
&#xD;
        1. Patients who have taken any medication for OLP within 4 weeks before the start of study.&#xD;
&#xD;
        2. Pregnant and lactating women.&#xD;
&#xD;
        3. History of lichenoid reactions to beta blockers, dapsone, oral hypoglycemics, NSAIDS,&#xD;
           pencillamine, phenothiazines, sulfonylureas, gold salts or amalgam fillings.&#xD;
&#xD;
           Sample Size All consecutive OLP patients will be evaluated according to&#xD;
           inclusion/exclusion criteria and at least 32 subjects will be enrolled they will be&#xD;
           randomly divided into study and control groups.&#xD;
&#xD;
           The sample size is calculated by the following formula keeping the power of study equal&#xD;
           to 90% and level of significance equal to 0.05. The sample size should be 16 in each&#xD;
           group.&#xD;
&#xD;
           [p1(1 - p1) + p2 (1 - p2)] n = × cp,power (p1 - p2)2 (Whitley and Ball, 2002) Desired&#xD;
           Level of Significance = 0.05 P1= proportion 1= 70% (0.7) P2= proportion 2= 30% (0.3) Cp,&#xD;
           power = 90% =10.5 Sample size in each group = 16 Randomization Randomization will be&#xD;
           done by allowing each patient to pick a sealed envelope from a box containing 40&#xD;
           envelopes of which 20 are of study and 20 are of control group.&#xD;
&#xD;
           Study Variables Socio-demographic/Medical parameters • Age (years), • Gender (male /&#xD;
           female), • Education (no-education / secondary / University), • Income (&lt;10000.00- /&#xD;
           10-20000.00 / &gt;20000.00),&#xD;
&#xD;
           • Smoking (never / former / current),&#xD;
&#xD;
           • Systemic conditions (CVD / DM / Hepatic / Rheumatoid Arthritis etc),&#xD;
&#xD;
           • Medications&#xD;
&#xD;
           • Oral hygiene habits (brushing, floss, dental visit)&#xD;
&#xD;
           Oral parameters&#xD;
&#xD;
             -  Dimensions of lesion will be measured by with the help of a UNC-12 probe (HDL®&#xD;
                Pakistan).&#xD;
&#xD;
             -  Color of lesion will be recorded by standardized pre and post treatment&#xD;
                photographic record.&#xD;
&#xD;
             -  Pain or burning sensation will be evaluated by visual analogue scale (VAS).&#xD;
&#xD;
             -  Clinical response (improvement of lesions and symptoms) will be assessed by&#xD;
                criteria given by (Escudier et al., 2007).&#xD;
&#xD;
           Data Collection Method and Instruments After approval from the ethical review committee,&#xD;
           patients will be included in the study. Written informed consent will be obtained from&#xD;
           all patients prior to the study as a part of ethical practice. 40 patients of&#xD;
           symptomatic OLP will be enrolled in the study after evaluation through punch biopsy and&#xD;
           other inclusion and exclusion criteria to compensate the loss to follow up as the actual&#xD;
           size calculated from the formula was 32. They will be randomly divided in to study and&#xD;
           control group each containing 20 patients. At baseline visit after recording the&#xD;
           socio-demographic and oral parameters data the local irritant factors in the oral cavity&#xD;
           which can aggravate the OLP will be removed by doing basic oral procedures like scaling&#xD;
           and root planning restorations, rounding of sharp cusps and replacement of any ill&#xD;
           fitting appliances in both the groups.&#xD;
&#xD;
           Study group will be given a cocktail containing dexamethasone, doxycycline, nystatin and&#xD;
           promethazine and will be advised to rinse with 1 and half teaspoon of this cocktail 3&#xD;
           times a day for 2 minutes for the period of 8 weeks and do not eat or drink anything 30&#xD;
           minutes after its use. Study group will also advised to apply triamcinolone orabase&#xD;
           containing 0.1% triamcinolone on lesions 3 times a day for the period of 8 weeks. The&#xD;
           control group will be advised to apply only triamcinolone orabase 3 times a day for 8&#xD;
           weeks with the same protocol. Assessment of dimension of lesions, color, pain and&#xD;
           burning sensation and improvement of lesions and symptoms will be done at baseline and&#xD;
           after 4 and 8 weeks.&#xD;
&#xD;
           Statistical Analysis The data will be coded and entered using SPSS ver 20. All the&#xD;
           numerical variables will be presented as mean and standard deviation while the&#xD;
           categorical variables will be reported as frequencies and percentages. the comparison of&#xD;
           efficacy between two groups will be done through chi-square test.&#xD;
&#xD;
           For all analysis a p-value of &gt; 0.05 will be considered significant with a confidence&#xD;
           level of 95%&#xD;
&#xD;
           Ethical Considerations:&#xD;
&#xD;
           Patients fulfilling the inclusion criteria will be informed about the aim of study,&#xD;
           risks, benefits and a consent form will be signed by them. Study will be approved by&#xD;
           Institutional Review Board (IRB), The University of Faisalabad.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">June 1, 2017</start_date>
  <completion_date type="Anticipated">December 31, 2017</completion_date>
  <primary_completion_date type="Anticipated">December 1, 2017</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>healing of lesions</measure>
    <time_frame>6 bmonths</time_frame>
    <description>healing of oral lichen planus lesions</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">32</enrollment>
  <condition>Oral Lichen Planus</condition>
  <arm_group>
    <arm_group_label>Study Group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>in this group patients will be treated with Dexamethasone local application</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>in this group patients will be treated with dexamethasone, doxycycline and nystattin</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexamethasone</intervention_name>
    <description>Dexamethasone will be applied locally on the lesion</description>
    <arm_group_label>Control Group</arm_group_label>
    <arm_group_label>Study Group</arm_group_label>
    <other_name>Doxycycline, Nystatin, Promethazine, Triamcinolone Orabase</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        - 1. Histopathologically proven patients of OLP of all age groups complaining of symptoms&#xD;
        such as pain, burning sensitivity to hot and spicy food.&#xD;
&#xD;
        2. Who have signed informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        - 1. Patients who have taken any medication for OLP within 4 weeks before the start of&#xD;
        study.&#xD;
&#xD;
        2. Pregnant and lactating women. 3. History of lichenoid reactions to beta blockers,&#xD;
        dapsone, oral hypoglycemics, NSAIDS, pencillamine, phenothiazines, sulfonylureas, gold&#xD;
        salts or amalgam fillings.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Saima Chaudhry, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Co-coordinator</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Sadaf Rashid, BDS</last_name>
    <phone>+923237791689</phone>
    <email>durr_e_sadaf@hotmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Arsalan Wahid, M.Phil</last_name>
    <phone>+923216685228</phone>
    <email>dr.arsalanmalik@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>The university of Faisalabad</name>
      <address>
        <city>Faisalābād</city>
        <state>Punjab</state>
        <zip>38000</zip>
        <country>Pakistan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sadaf Rashid, BDS</last_name>
      <phone>+923237791689</phone>
      <email>durr_e_sadaf@hotmail.com</email>
    </contact>
    <contact_backup>
      <last_name>Arsalan Wahid, M. Phil</last_name>
      <phone>+923216685228</phone>
      <email>dr.arsalanmalik@gmail.com</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Pakistan</country>
  </location_countries>
  <verification_date>July 2017</verification_date>
  <study_first_submitted>July 29, 2017</study_first_submitted>
  <study_first_submitted_qc>July 29, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 2, 2017</study_first_posted>
  <last_update_submitted>July 29, 2017</last_update_submitted>
  <last_update_submitted_qc>July 29, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 2, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Faisalabad</investigator_affiliation>
    <investigator_full_name>Durr-e-Sadaf</investigator_full_name>
    <investigator_title>Demonstrator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lichen Planus, Oral</mesh_term>
    <mesh_term>Lichen Planus</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Promethazine</mesh_term>
    <mesh_term>Doxycycline</mesh_term>
    <mesh_term>Nystatin</mesh_term>
    <mesh_term>Dexamethasone</mesh_term>
    <mesh_term>Triamcinolone</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03237533
org study id: 123456789
nct id: NCT03237533
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Background: Oral lichen planus (OLP) is a chronic inflammatory mucocutaneous autoimmune
      disease mainly affecting stratum basal of the epithelium. It is very painful and hamper the
      daily routine of patients e.g. (talking, drinking, eating, maintaining normal relationships).
      Different topical treatments have been tried for the symptomatic relief of OLP which include
      topical corticosteroids (TCSs), topical calcineurin inhibitors (TCIs) retinoids,
      photochemotherapy; amitryptaline; thalidomide; amlexanox and traditional medicines such as
      curcumin, selenium-ACE combined with itraconazole, glycyrrhiza glabra and aloe vera. But the
      exact treatment is still unknown.

      Objective: To compare the efficacy of Dexamethasone, Doxycycline, Nystatin and Promethazine
      cocktail with Triamcinolone as topical treatment of OLP Subjects and Methods: 40 patients of
      symptomatic OLP will be randomly divided in to study and control group. Study group will be
      given a cocktail containing dexamethasone, doxycycline, nystatin and promethazine and will be
      advised to rinse with 1 and half teaspoon of this cocktail 3 times a day for 2 minutes for
      the period of 8 weeks. Study group is also advised to apply an orabase containing 0.1%
      triamcinolone on lesions 3 times a day for the period of 8 weeks. The control group will be
      advised to apply only triamcinolone orabase 3 times a day for 8 weeks.
Introduction Oral lichen planus (OLP) is a chronic inflammatory mucocutaneous autoimmune
      disease mainly affecting stratum basal of the epithelium. It is T-cell mediated immunological
      disease that mostly occurs bilaterally on buccal mucosa while tongue and gingiva are other
      commonly involved sites while palatal mucosa and floor of the mouth are rarely affected
      (Roopashree MR, 2010, Torrente-Castells et al., 2010, Alves et al, 2010). The prevalence of
      OLP in general population is 0.1-4% (Sugerman et al., 2002) mainly affecting the middle-aged
      and elderly people (Ingafou et al., 2006) and female: male ratio 2:1 (Shen et al., 2012).

      It has six clinical forms: keratotic, reticular, papular, plaquelike white patches, erosive,
      atrophic, and bullous (Shen et al., 2012). Reticular and erosive form are most common (Alves
      et al, 2010). Keratotic reticular, papular, plaque like white patches often present with no
      complaints (Oczko et al, 2011), while erosive, atrophic, and ulcerative lesions are a painful
      or present with a burning sensation, and thus make eating, speaking, and swallowing difficult
      (Thongprasom et al., 2007). Histologically, a subepithelial infiltration in the form of dense
      band of lymphocytes, increased numbers of intraepithelial lymphocytes and the liquefaction
      degeneration of basal keratinocytes is seen in OLP (Payeras et al., 2013).

      Several predisposing factors have been identified which may cause or progress OLP which
      include immunity, infection, genetics, stress and endocrine. Recent researches showed an
      increased activity of prolidase and oxidative stress in OLP patients, causing disturbance in
      the antioxidant defense system (Batu et al, 2016, Ergun et al, 2011). Although the exact
      cause is still not clear, facts show that an immunological process is involved in OLP which
      is activated by an unknown antigen that change the basal keratinocytes of the oral mucosa and
      these alterations cause the cell immune response to attack the keratinocytes. (Ismail et al.,
      2007, Payeras et al., 2013). This antigen may be intrinsic or extrinsic, or both. Evidence
      shows that bacteria can be one of the etiologic factors of OLP. An association has already
      been found between OLP and infection, such as Ebstein Barr virus, Hepatitis C virus,
      Helicobacter pylori and Candida Albicans. A study also pointed out the allergy to various
      antigens coming in direct contact with oral cavity to contribute to the etiology of OLP. (D.
      Wray, 2000) As the etiology is not known therefore there is no definitive treatment for OLP
      and the mainstay of therapy for improving the life of these patients is symptomatic topical
      treatment. Topical treatments which have been tried for the symptomatic OLP include topical
      corticosteroids (TCSs), including betamethasone, clobetasol, dexamethasone and triamcinolone;
      topical calcineurin inhibitors (TCIs) such as pimecrolimus, tacrolimus or ciclosporin;
      retinoids such as tretinoin; photochemotherapy; amitryptaline; thalidomide; amlexanox and
      traditional medicines such as curcumin, selenium-ACE combined with itraconazole, glycyrrhiza
      glabra and aloe vera.

      In a study both tacrolimus 0.1% ointment and pimecrolimus 1% cream were found equally
      effective for the treatment of OLP (Vohra et al., 2016). Similarly another study showed that
      Clobetasol propionate (0.05%) was found more effective than triamcinolone acetonate (0.1%)
      and tacrolimus orabase (0.03%) for the management of OLP. This study also found that
      triamcinolone 0.1% is superior to tacrolimus 0.03% in terms of effectiveness for the
      treatment of OLP.(Sivaraman et al., 2016) According to another study both triamcinolone and
      curcumin paste were found almost equally effective in reducing the pain and improving the
      appearance of OLP lesions (Kia et al., 2015). In another study it was concluded that
      combination of Selenium-ACE, corticosteroid and antifungal is a better treatment regimen for
      the treatment of erosive ulcerative OLP than a capsule of 100 mg Itraconazole plus
      dexamethsone mouthwash or dexamethasone alone (Belal, 2015). In another similar study
      cocktail of clobetasol, ketoconazole and amitryptiline was found more efficacious than
      diluted dexamethasone, nystatin and Diphenhydramine elixir (Javadzadeh et al, 2008). In a
      comparative study tacrolimus 0.1% cream was found more effective than 0.05% clobetasol
      propionate cream in reducing pain and healing of OLP lesions (Hettiarachchi et al., 2016).
      Both thalidomide and dexamethasone were found almost equally effective in another trail (Wu
      et al., 2010). In a trail of comperison between amlexanox paste and dexamethasone paste both
      were found equally effective at the end of 7 days in terms of reduction in clinical signs
      (erosion) and symptoms like pain and burning sensation (Fu et al., 2012). Some herbal
      medicines have also been tried like Glycyrrhiza glabra and Aloe vera, in a trail to compare
      the efficacy of 1% Glycyrrhiza glabra In orabase with 0.1% Triamcinolone Acetonide both were
      found almost equally effective in reducing the pain and improving the appearance of OLP
      lesions (Najafi et al., 2016) and in another trail both Aloe Vera Mouthwash and Triamcinolone
      Acetonide were found almost equally effective in reducing the pain and in reducing the size
      of OLP lesions (Mansourian et al., 2011) So steroids remained the mainstay of treatment for
      OLP but evidence points towards the involvement of bacterial and fungal infections in the
      pathogenesis of OLP as according to a recent study disbiosis was found in the buccal surface
      mucosa of patients of OLP, as certain bacterial species were found in greater no in buccal
      mucosa of OLP patients so they concluded that an association exists between bacterial
      disbiosis of buccal mucosa and OLP (He et al., 2017). Similar studies showed that antibiotics
      relieved symptoms of OLP effectively (Backman & Jontell, 2007; Carbone et al, 1999). OLP is a
      disease which reduces the individual's resistance and changes the candida albican's role from
      commensalism to parasitism which is among the normal flora of oral cavity or candida may
      secondarily infect the OLP lesions and exacerbate the signs and symptoms (santosh gowdru
      shivanandappa, 2012). In a study 62% of OLP patients were found allergic to different
      allergens which come in contact with mucosa in daily life so they found that association
      exists between OLP and allergy (D. Wray, 2000). According to another study mast cell
      hyperplasia was seen in OLP patients which suggests their role in pathogenesis of OLP (Ankle
      R et al, 2007) The most used therapy is TCSs however its effectiveness is limited due to
      opportunistic oral infections in patients with OLP. Adjunct antibiotic therapies have been
      used to aid in symptomatic relief and improved response has been observed as compared to TCSs
      alone. however none of the combined therapies have used antifungal as an additive in their
      local applications, as candida is one of the opportunistic organisms that colonizes affected
      sites. Role of allergy mechanisms have also been discussed.

      Rationale Evidence of involvement of bacterial and fungal infections and allergy in the
      pathogenesis of OLP suggests the need for the use of antibiotic, anti fungal and
      antihistamine for the topical treatment of OLP and there is a gap in literature. That's why
      current trail is being done to evaluate the efficacy of topical doxycycline, nyastatin and
      promethazine along with dexamethasone for the symptomatic relief of OLP.

      Hypothesis Dexamethasone, Doxycycline, Nystatin and Promethazine combination topical rinse
      are more effective for the treatment of OLP than Triamcinolone alone Objective To compare the
      efficacy of Dexamethasone, Doxycycline, Nystatin and Promethazine combination topical rinse
      with Triamcinolone rinse as topical treatment of Oral Lichen Planus.

      Operational Definitions • Oral Lichen Planus: Oral lichen planus (OLP) is a chronic
      inflammatory mucocutaneous autoimmune disease mainly affecting stratum basal of the
      epithelium.

      Subjects and Methods Study Type Randomized control trail (Parallel arm study). Study Setting
      Department of Oral Medicine & Diagnosis and Department of Dermatology. Madina Teaching
      Hospital Faisalabad.

      Duration The study will be completed in 3 months after the approval of synopsis. Study
      Population Patients of oral lichen planus visiting Department of Oral Medicine & Diagnosis
      and Department of Dermatology. Madina Teaching Hospital Faisalabad.

      Sampling Technique Purposive Sampling, (Inclusion/exclusion criteria based)

      Sample Selection Inclusion Criteria

        1. Histopathologically proven patients of OLP of all age groups complaining of symptoms
           such as pain, burning sensitivity to hot and spicy food.

        2. Who have signed informed consent. Exclusion Criteria

        1. Patients who have taken any medication for OLP within 4 weeks before the start of study.

        2. Pregnant and lactating women.

        3. History of lichenoid reactions to beta blockers, dapsone, oral hypoglycemics, NSAIDS,
           pencillamine, phenothiazines, sulfonylureas, gold salts or amalgam fillings.

           Sample Size All consecutive OLP patients will be evaluated according to
           inclusion/exclusion criteria and at least 32 subjects will be enrolled they will be
           randomly divided into study and control groups.

           The sample size is calculated by the following formula keeping the power of study equal
           to 90% and level of significance equal to 0.05. The sample size should be 16 in each
           group.

           [p1(1 - p1) + p2 (1 - p2)] n = × cp,power (p1 - p2)2 (Whitley and Ball, 2002) Desired
           Level of Significance = 0.05 P1= proportion 1= 70% (0.7) P2= proportion 2= 30% (0.3) Cp,
           power = 90% =10.5 Sample size in each group = 16 Randomization Randomization will be
           done by allowing each patient to pick a sealed envelope from a box containing 40
           envelopes of which 20 are of study and 20 are of control group.

           Study Variables Socio-demographic/Medical parameters • Age (years), • Gender (male /
           female), • Education (no-education / secondary / University), • Income (<10000.00- /
           10-20000.00 / >20000.00),

           • Smoking (never / former / current),

           • Systemic conditions (CVD / DM / Hepatic / Rheumatoid Arthritis etc),

           • Medications

           • Oral hygiene habits (brushing, floss, dental visit)

           Oral parameters

             -  Dimensions of lesion will be measured by with the help of a UNC-12 probe (HDL®
                Pakistan).

             -  Color of lesion will be recorded by standardized pre and post treatment
                photographic record.

             -  Pain or burning sensation will be evaluated by visual analogue scale (VAS).

             -  Clinical response (improvement of lesions and symptoms) will be assessed by
                criteria given by (Escudier et al., 2007).

           Data Collection Method and Instruments After approval from the ethical review committee,
           patients will be included in the study. Written informed consent will be obtained from
           all patients prior to the study as a part of ethical practice. 40 patients of
           symptomatic OLP will be enrolled in the study after evaluation through punch biopsy and
           other inclusion and exclusion criteria to compensate the loss to follow up as the actual
           size calculated from the formula was 32. They will be randomly divided in to study and
           control group each containing 20 patients. At baseline visit after recording the
           socio-demographic and oral parameters data the local irritant factors in the oral cavity
           which can aggravate the OLP will be removed by doing basic oral procedures like scaling
           and root planning restorations, rounding of sharp cusps and replacement of any ill
           fitting appliances in both the groups.

           Study group will be given a cocktail containing dexamethasone, doxycycline, nystatin and
           promethazine and will be advised to rinse with 1 and half teaspoon of this cocktail 3
           times a day for 2 minutes for the period of 8 weeks and do not eat or drink anything 30
           minutes after its use. Study group will also advised to apply triamcinolone orabase
           containing 0.1% triamcinolone on lesions 3 times a day for the period of 8 weeks. The
           control group will be advised to apply only triamcinolone orabase 3 times a day for 8
           weeks with the same protocol. Assessment of dimension of lesions, color, pain and
           burning sensation and improvement of lesions and symptoms will be done at baseline and
           after 4 and 8 weeks.

           Statistical Analysis The data will be coded and entered using SPSS ver 20. All the
           numerical variables will be presented as mean and standard deviation while the
           categorical variables will be reported as frequencies and percentages. the comparison of
           efficacy between two groups will be done through chi-square test.

           For all analysis a p-value of > 0.05 will be considered significant with a confidence
           level of 95%

           Ethical Considerations:

           Patients fulfilling the inclusion criteria will be informed about the aim of study,
           risks, benefits and a consent form will be signed by them. Study will be approved by
           Institutional Review Board (IRB), The University of Faisalabad.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: healing of lesions
time frame: 6 bmonths
description: healing of oral lichen planus lesions
arm group label: Study Group
arm group type: Active Comparator
description: in this group patients will be treated with Dexamethasone local application
arm group label: Control Group
arm group type: Active Comparator
description: in this group patients will be treated with dexamethasone, doxycycline and nystattin
intervention type: Drug
intervention name: Dexamethasone
description: Dexamethasone will be applied locally on the lesion
arm group label: Control Group
arm group label: Study Group
other name: Doxycycline, Nystatin, Promethazine, Triamcinolone Orabase
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Saima Chaudhry, PhD
role: Study Director
affiliation: Co-coordinator
last name: Sadaf Rashid, BDS
phone: +923237791689
email: durr_e_sadaf@hotmail.com
last name: Arsalan Wahid, M.Phil
phone: +923216685228
email: dr.arsalanmalik@gmail.com
facility: 
status: Recruiting
contact: 
contact backup: 
country: Pakistan
responsible party type: Principal Investigator
investigator affiliation: University of Faisalabad
investigator full name: Durr-e-Sadaf
investigator title: Demonstrator
mesh term: Lichen Planus, Oral
mesh term: Lichen Planus
mesh term: Promethazine
mesh term: Doxycycline
mesh term: Nystatin
mesh term: Dexamethasone
mesh term: Triamcinolone
sharing ipd: No