<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/NCT04476420</url>
  </required_header>
  <id_info>
    <org_study_id>2130520HBOM</org_study_id>
    <nct_id>NCT04476420</nct_id>
  </id_info>
  <brief_title>Comparative Effect of Nigella Sativa and Conventional Management for OSMF</brief_title>
  <official_title>Comparison of Nigella Sativa Oil With Conventional Management on Clinical Outcomes in Oral Submucous Fibrosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ziauddin University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ziauddin University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Oral submucous fibrosis (OSMF) is a potentially malignant condition mainly characterized by&#xD;
      inflammation and fibrosis of the submucosal tissues leading to marked rigidity and reduced&#xD;
      opening of the jaws. OSMF has a multifactorial etiology but areca nut consumption is&#xD;
      considered to be the most consistent factor in its pathogenesis. There is no definitive&#xD;
      treatment available for treating OSMF. Conventional management involves physiotherapy&#xD;
      exercises and treating the disease with certain medications such as steroids and homeopathic&#xD;
      medications.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      OSMF is a chronic insidious disorder of the oral cavity which has a great potential to turn&#xD;
      malignant. The clinical manifestations of OSMF comprise of white, marble-like appearance of&#xD;
      the oral mucosa with loss of flexibility and formation of palpable fibrous bands extending&#xD;
      from the anterior to the posterior region of the oral cavity.Other features include burning&#xD;
      sensation on taking spicy food, loss of papillae of the tongue, loss of natural pigmentation&#xD;
      of the lips and restricted mouth opening.&#xD;
&#xD;
      There is no definitive treatment available for OSMF due to its complex etiology. The most&#xD;
      essential component in the management of OSMF is the discontinuation of the habit of areca&#xD;
      nut chewing by the patient followed by conservative or surgical treatment. Currently,&#xD;
      steroids are the most commonly used drug group in managing OSMF because of their ability to&#xD;
      reduce the inflammatory process and increasing the apoptosis of inflammatory cells thereby&#xD;
      decreasing fibrosis. However, they are not very useful in reversing the pathology and&#xD;
      restoring mucosal elasticity and can cause mucosal thinning with long term use ultimately&#xD;
      resulting in worsening of the symptoms of the disease.&#xD;
&#xD;
      Many in- vitro and in- vivo studies have been conducted to establish the anti neoplastic,&#xD;
      anti inflammatory, immunomodulatory, antihypertensive, antimicrobial, anti-parasitic,&#xD;
      antioxidant and hypoglycemic properties of N.sativa oil. Among all the constituents of&#xD;
      Nigella sativa, Thymoquinone (Tq) is the most pharmacologically active constituent&#xD;
      responsible for most of its properties. Nigella sativa has been used widely in different food&#xD;
      preparations in the form of a flavoring agent or a spice. It is also recognized as 'safe' in&#xD;
      the inventory of United States Food and Drug administration.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 11, 2021</start_date>
  <completion_date type="Actual">September 30, 2021</completion_date>
  <primary_completion_date type="Actual">September 30, 2021</primary_completion_date>
  <phase>Phase 3</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pain assessed using visual analogue scale (VAS)</measure>
    <time_frame>6 months</time_frame>
    <description>Pain will be measured using VAS. This scale usually present as a 100-mm horizontal line on which the pain intensity experienced by the patient will be represented by a point between the extremes of &quot;no pain at all&quot; and &quot;worst pain imaginable.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Inter-incisal mouth opening (IMO) assessed using vernier caliper</measure>
    <time_frame>6 months</time_frame>
    <description>Interincisal mouth opening will be calculated by measuring the distance between the mesioincisal angles of the maxillary central incisor and the mandibular central incisor with the help of a vernier calliper.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cheek Flexibility assessed following the method of Mathur and Jha (1993)</measure>
    <time_frame>6 months</time_frame>
    <description>A line will be drawn from the tragus of the ear to the angle of the mouth and then two reference points will be marked on both the cheeks at 1/3rd the distance from the angle of the mouth on the line drawn previously. After marking these reference points, the patient will be asked to blow his cheek and the distance will be measured between the two points. Then the patient will be instructed to relax his cheeks and the distance will be measured again. The difference between the two values will give the value for cheek flexibility.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tongue protrusion</measure>
    <time_frame>6 months</time_frame>
    <description>Tongue protrusion will be recorded by measuring the distance between the tip of the tongue and the mesioincisal angle of the upper central incisor using steel ruler.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">39</enrollment>
  <condition>Oral Submucous Fibrosis</condition>
  <arm_group>
    <arm_group_label>Steroid group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants in group 1 will be given corticosteroid lotion (Betamethasone valerate 0.1%) and will be advised to apply it topically (0.5 ml) on the buccal mucosa thrice a day along with physiotherapy using ice cream sticks three times a day for the duration of 10 minutes (3-5minutes on each side).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Nigella Sativa oil group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Group 2 will be given commercially available, cold pressed N.sativa (Black seed) oil and will be advised to apply it topically over the buccal mucosa (1 ml) thrice a day along with physiotherapy using ice cream sticks three times a day for the duration of 10 minutes (3-5minutes on each side).</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Nigella sativa oil</intervention_name>
    <description>Using N.sativa oil as an alternative to conventional management will help us to find a treatment option which is non-invasive, cost effective, inexpensive, easy available and belongs to a natural source with almost no side effects.</description>
    <arm_group_label>Nigella Sativa oil group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Betamethasone Valerate</intervention_name>
    <description>it is a conventionally used drug for treating OSMF</description>
    <arm_group_label>Steroid group</arm_group_label>
    <other_name>Corticosteroid</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with the age of 18 years and above&#xD;
&#xD;
          -  Patients clinically diagnosed with Oral submucous fibrosis&#xD;
&#xD;
          -  Patients who have not received any treatment for Oral submucous fibrosis in the last&#xD;
             three months.&#xD;
&#xD;
          -  Patients who are willing to quit the habit of eating pan, gutka and areca nut&#xD;
&#xD;
          -  Patients who are willing to attend the follow up visits&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who are less than 18 years of age&#xD;
&#xD;
          -  Patients who are already using pain medications, corticosteroids or immunosuppressive&#xD;
             drugs in any other form&#xD;
&#xD;
          -  Patients with a history of malignancy&#xD;
&#xD;
          -  Patients presenting with oral lesions other than Oral submucous fibrosis (OSMF)&#xD;
&#xD;
          -  Patients who are allergic to the drug material used in the clinical trial&#xD;
&#xD;
          -  Patients who will not give consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hira Batool, Mphil</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ziauddin University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Ziauddin University, Clifton</name>
      <address>
        <city>Karachi</city>
        <state>Sindh</state>
        <zip>75600</zip>
        <country>Pakistan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Pakistan</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>July 2, 2020</study_first_submitted>
  <study_first_submitted_qc>July 14, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 20, 2020</study_first_posted>
  <last_update_submitted>March 14, 2022</last_update_submitted>
  <last_update_submitted_qc>March 14, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 15, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Ziauddin University</investigator_affiliation>
    <investigator_full_name>Hira Batool</investigator_full_name>
    <investigator_title>Doctor</investigator_title>
  </responsible_party>
  <keyword>OSMF</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Oral Submucous Fibrosis</mesh_term>
    <mesh_term>Fibrosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Betamethasone</mesh_term>
    <mesh_term>Betamethasone Valerate</mesh_term>
    <mesh_term>Betamethasone-17,21-dipropionate</mesh_term>
    <mesh_term>Betamethasone benzoate</mesh_term>
    <mesh_term>Betamethasone sodium phosphate</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/NCT04476420
org study id: 2130520HBOM
nct id: NCT04476420
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
Oral submucous fibrosis (OSMF) is a potentially malignant condition mainly characterized by
      inflammation and fibrosis of the submucosal tissues leading to marked rigidity and reduced
      opening of the jaws. OSMF has a multifactorial etiology but areca nut consumption is
      considered to be the most consistent factor in its pathogenesis. There is no definitive
      treatment available for treating OSMF. Conventional management involves physiotherapy
      exercises and treating the disease with certain medications such as steroids and homeopathic
      medications.
OSMF is a chronic insidious disorder of the oral cavity which has a great potential to turn
      malignant. The clinical manifestations of OSMF comprise of white, marble-like appearance of
      the oral mucosa with loss of flexibility and formation of palpable fibrous bands extending
      from the anterior to the posterior region of the oral cavity.Other features include burning
      sensation on taking spicy food, loss of papillae of the tongue, loss of natural pigmentation
      of the lips and restricted mouth opening.

      There is no definitive treatment available for OSMF due to its complex etiology. The most
      essential component in the management of OSMF is the discontinuation of the habit of areca
      nut chewing by the patient followed by conservative or surgical treatment. Currently,
      steroids are the most commonly used drug group in managing OSMF because of their ability to
      reduce the inflammatory process and increasing the apoptosis of inflammatory cells thereby
      decreasing fibrosis. However, they are not very useful in reversing the pathology and
      restoring mucosal elasticity and can cause mucosal thinning with long term use ultimately
      resulting in worsening of the symptoms of the disease.

      Many in- vitro and in- vivo studies have been conducted to establish the anti neoplastic,
      anti inflammatory, immunomodulatory, antihypertensive, antimicrobial, anti-parasitic,
      antioxidant and hypoglycemic properties of N.sativa oil. Among all the constituents of
      Nigella sativa, Thymoquinone (Tq) is the most pharmacologically active constituent
      responsible for most of its properties. Nigella sativa has been used widely in different food
      preparations in the form of a flavoring agent or a spice. It is also recognized as 'safe' in
      the inventory of United States Food and Drug administration.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Pain assessed using visual analogue scale (VAS)
time frame: 6 months
description: Pain will be measured using VAS. This scale usually present as a 100-mm horizontal line on which the pain intensity experienced by the patient will be represented by a point between the extremes of "no pain at all" and "worst pain imaginable.
measure: Inter-incisal mouth opening (IMO) assessed using vernier caliper
time frame: 6 months
description: Interincisal mouth opening will be calculated by measuring the distance between the mesioincisal angles of the maxillary central incisor and the mandibular central incisor with the help of a vernier calliper.
measure: Cheek Flexibility assessed following the method of Mathur and Jha (1993)
time frame: 6 months
description: A line will be drawn from the tragus of the ear to the angle of the mouth and then two reference points will be marked on both the cheeks at 1/3rd the distance from the angle of the mouth on the line drawn previously. After marking these reference points, the patient will be asked to blow his cheek and the distance will be measured between the two points. Then the patient will be instructed to relax his cheeks and the distance will be measured again. The difference between the two values will give the value for cheek flexibility.
measure: Tongue protrusion
time frame: 6 months
description: Tongue protrusion will be recorded by measuring the distance between the tip of the tongue and the mesioincisal angle of the upper central incisor using steel ruler.
arm group label: Steroid group
arm group type: Active Comparator
description: Participants in group 1 will be given corticosteroid lotion (Betamethasone valerate 0.1%) and will be advised to apply it topically (0.5 ml) on the buccal mucosa thrice a day along with physiotherapy using ice cream sticks three times a day for the duration of 10 minutes (3-5minutes on each side).
arm group label: Nigella Sativa oil group
arm group type: Experimental
description: Group 2 will be given commercially available, cold pressed N.sativa (Black seed) oil and will be advised to apply it topically over the buccal mucosa (1 ml) thrice a day along with physiotherapy using ice cream sticks three times a day for the duration of 10 minutes (3-5minutes on each side).
intervention type: Dietary Supplement
intervention name: Nigella sativa oil
description: Using N.sativa oil as an alternative to conventional management will help us to find a treatment option which is non-invasive, cost effective, inexpensive, easy available and belongs to a natural source with almost no side effects.
arm group label: Nigella Sativa oil group
intervention type: Drug
intervention name: Betamethasone Valerate
description: it is a conventionally used drug for treating OSMF
arm group label: Steroid group
other name: Corticosteroid
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Hira Batool, Mphil
role: Principal Investigator
affiliation: Ziauddin University
facility: 
country: Pakistan
responsible party type: Principal Investigator
investigator affiliation: Ziauddin University
investigator full name: Hira Batool
investigator title: Doctor
mesh term: Oral Submucous Fibrosis
mesh term: Fibrosis
mesh term: Betamethasone
mesh term: Betamethasone Valerate
mesh term: Betamethasone-17,21-dipropionate
mesh term: Betamethasone benzoate
mesh term: Betamethasone sodium phosphate
sharing ipd: No