<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/NCT03252418</url>
  </required_header>
  <id_info>
    <org_study_id>FDASU-RECIM10201512</org_study_id>
    <nct_id>NCT03252418</nct_id>
  </id_info>
  <brief_title>Ascorbic Acid Versus Diode Laser in the Treatment of Gingival Hyperpigmentation</brief_title>
  <official_title>Ascorbic Acid Versus Diode Laser in the Treatment of Gingival Hyperpigmentation: Histological and Clinical Randomized Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ain Shams University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ain Shams 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>
  </oversight_info>
  <brief_summary>
    <textblock>
      Vitamin C affect the melanocytes function not the number while diode laser cause melanocytes&#xD;
      destruction. Although diode laser and vitamin C have proved their effectiveness in&#xD;
      depigmentation in previous studies, there are no published studies compared the effect of&#xD;
      diode laser and vitamin C on melanocytes and melanosomes clinically and histologically.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Cosmetic dentistry is usually centered on aesthetic restorative procedures but it may also&#xD;
      involve the appearance of the gingiva, especially when it is located in the anterior labial&#xD;
      region. Oral pigmentation may be physiological or pathological in nature. Better esthetics&#xD;
      results of depigmentation were achieved with diode laser than conventional scalpel and with&#xD;
      rotary abrasion, also diode laser is effective and safe in removal of gingival&#xD;
      hyperpigmentation and repigmentation doesn't occur.When choosing a depigmenting agent, it is&#xD;
      important to differentiate between substances that are toxic to the melanocyte and substances&#xD;
      that interrupt the key steps of melanogenesis. Vit. C interacts with copper ions at the&#xD;
      tyrosinase-active site and inhibits action of the enzyme tyrosinase, thereby decreasing the&#xD;
      melanin formation.&#xD;
&#xD;
      This randomized comparative clinical study was conducted on ten patients attending the&#xD;
      outpatient clinic of the Oral Medicine and Periodontology department, Faculty of Dentistry,&#xD;
      Ain Shams University and seeking treatment for their gingival hyperpigmentation for esthetic&#xD;
      reason.&#xD;
&#xD;
      The study was conducted after receiving an ethical clearance from the Research Ethics&#xD;
      Committee of Ain Shams University, Faculty of Dentistry; that the study follows the ethical&#xD;
      guidelines of research. The patients clearly understood the purpose of this study and signed&#xD;
      an informed consent.&#xD;
&#xD;
      According to the study results, vit C treated patients showed no or little repigmentation&#xD;
      after six months post treatment. Conversely, diode laser treated patients showed significant&#xD;
      recurrence of gingival pigmentation after six months post treatment. These could be&#xD;
      attributed to the blocking effect of vitamin C on the existing melanocytes to form new&#xD;
      melanoseomes, however diode laser cause removal of the existing melanocytes that may cause&#xD;
      formation of new melanocytes (migrating from neighboring melanocytes from the adjacent area&#xD;
      of the gingiva) with the ability of forming new melanosomes and causing repigmentation.&#xD;
      Histopathological assessment revealed that both treatment modalities caused significant&#xD;
      reduction in MAF after six months post treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 7, 2015</start_date>
  <completion_date type="Actual">September 10, 2016</completion_date>
  <primary_completion_date type="Actual">September 10, 2016</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>treating of gingival hyperpigmentation by two different methods</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>when measuring the gingival brightness and MAF of melanosomes</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Dummett oral pigmentaion index (DOPI)</measure>
    <time_frame>change from baseline to 1, 3 and 6 months</time_frame>
    <description>scoring from 0 ( no pigmentation to 3 (sever pigmentation</description>
  </primary_outcome>
  <primary_outcome>
    <measure>gingival brightness (ΔL)</measure>
    <time_frame>change from baseline to 1, 3 and 6 months</time_frame>
    <description>using spectrophotometer</description>
  </primary_outcome>
  <primary_outcome>
    <measure>histological mean area fraction of melanosomes</measure>
    <time_frame>change from baseline to 6 months</time_frame>
    <description>by taking soft tissue samples and stained by fontana masson stain</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>patient satisfaction questionnaire</measure>
    <time_frame>immediate postopearive, 1 week, 1 month and 6 months</time_frame>
    <description>from scoring patients pain and cosmetic changes</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Gingival Hyperpigmentaion</condition>
  <arm_group>
    <arm_group_label>ascorbic acid</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>injection of 1 ml intamucosal ascorbic acid 3 times with 1 week interval</description>
  </arm_group>
  <arm_group>
    <arm_group_label>diode laser</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>photothermolysis by diode laser in one session</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ascorbic Acid 500 MG</intervention_name>
    <description>ascorbic acid is vitamin that can cause gingival depigmentation</description>
    <arm_group_label>ascorbic acid</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>diode laser</intervention_name>
    <description>diode laser is soft tissue laser case photothermolysis of melanoctes</description>
    <arm_group_label>diode laser</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male and female patients with age ranging from 18 years old to 40 years old.&#xD;
&#xD;
          -  Bilaterally symmetric gingival hyperpigmentation on the maxillary and mandibular&#xD;
             labial keratinized gingiva between canines.&#xD;
&#xD;
          -  Patients free from any systemic diseases as evidenced by the health questionnaire,&#xD;
             using modified Cornell medical index (Pendleton et al., 2004).&#xD;
&#xD;
          -  Patients with thick gingival biotype ≥ 3 mm.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Presence of local condition that may cause gingival hyperpigmentation (traumatized&#xD;
             epithelium caused by defective fixed prosthesis or restoration).&#xD;
&#xD;
          -  Smokers.&#xD;
&#xD;
          -  Pregnant or lactating females.&#xD;
&#xD;
          -  Patients with poor oral hygiene, incompliance to treatment and persistence gingival&#xD;
             inflammation after phase I periodontal therapy.&#xD;
&#xD;
          -  Clinically diagnosed periodontitis (attachment and bone loss, presence of periodontal&#xD;
             pockets, gingival recession and tooth mobility).&#xD;
&#xD;
          -  Previous treatment to pigmentation.&#xD;
&#xD;
          -  Patients taking supplementary vitamin C for any reason.&#xD;
&#xD;
          -  Known sensitivity to ascorbic acid or any of its derivatives.&#xD;
&#xD;
          -  Patients taking any drug that may cause gingival pigmentation.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nevine H kheir ElDien, Professor</last_name>
    <role>Study Director</role>
    <affiliation>faculty of Dentistry- Ain Shams univesity</affiliation>
  </overall_official>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>August 15, 2017</study_first_submitted>
  <study_first_submitted_qc>August 15, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 17, 2017</study_first_posted>
  <last_update_submitted>August 18, 2017</last_update_submitted>
  <last_update_submitted_qc>August 18, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 22, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Ain Shams University</investigator_affiliation>
    <investigator_full_name>Dalia Yosri</investigator_full_name>
    <investigator_title>Assistant lecturer of oral medicine and periodontology</investigator_title>
  </responsible_party>
  <keyword>ascorbic acid</keyword>
  <keyword>diode laser</keyword>
  <keyword>gingival hyperpigmentation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hyperpigmentation</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ascorbic Acid</mesh_term>
  </intervention_browse>
  <!-- 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/NCT03252418
org study id: FDASU-RECIM10201512
nct id: NCT03252418
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Vitamin C affect the melanocytes function not the number while diode laser cause melanocytes
      destruction. Although diode laser and vitamin C have proved their effectiveness in
      depigmentation in previous studies, there are no published studies compared the effect of
      diode laser and vitamin C on melanocytes and melanosomes clinically and histologically.
Cosmetic dentistry is usually centered on aesthetic restorative procedures but it may also
      involve the appearance of the gingiva, especially when it is located in the anterior labial
      region. Oral pigmentation may be physiological or pathological in nature. Better esthetics
      results of depigmentation were achieved with diode laser than conventional scalpel and with
      rotary abrasion, also diode laser is effective and safe in removal of gingival
      hyperpigmentation and repigmentation doesn't occur.When choosing a depigmenting agent, it is
      important to differentiate between substances that are toxic to the melanocyte and substances
      that interrupt the key steps of melanogenesis. Vit. C interacts with copper ions at the
      tyrosinase-active site and inhibits action of the enzyme tyrosinase, thereby decreasing the
      melanin formation.

      This randomized comparative clinical study was conducted on ten patients attending the
      outpatient clinic of the Oral Medicine and Periodontology department, Faculty of Dentistry,
      Ain Shams University and seeking treatment for their gingival hyperpigmentation for esthetic
      reason.

      The study was conducted after receiving an ethical clearance from the Research Ethics
      Committee of Ain Shams University, Faculty of Dentistry; that the study follows the ethical
      guidelines of research. The patients clearly understood the purpose of this study and signed
      an informed consent.

      According to the study results, vit C treated patients showed no or little repigmentation
      after six months post treatment. Conversely, diode laser treated patients showed significant
      recurrence of gingival pigmentation after six months post treatment. These could be
      attributed to the blocking effect of vitamin C on the existing melanocytes to form new
      melanoseomes, however diode laser cause removal of the existing melanocytes that may cause
      formation of new melanocytes (migrating from neighboring melanocytes from the adjacent area
      of the gingiva) with the ability of forming new melanosomes and causing repigmentation.
      Histopathological assessment revealed that both treatment modalities caused significant
      reduction in MAF after six months post treatment.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: treating of gingival hyperpigmentation by two different methods
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: when measuring the gingival brightness and MAF of melanosomes
measure: Dummett oral pigmentaion index (DOPI)
time frame: change from baseline to 1, 3 and 6 months
description: scoring from 0 ( no pigmentation to 3 (sever pigmentation
measure: gingival brightness (ΔL)
time frame: change from baseline to 1, 3 and 6 months
description: using spectrophotometer
measure: histological mean area fraction of melanosomes
time frame: change from baseline to 6 months
description: by taking soft tissue samples and stained by fontana masson stain
measure: patient satisfaction questionnaire
time frame: immediate postopearive, 1 week, 1 month and 6 months
description: from scoring patients pain and cosmetic changes
arm group label: ascorbic acid
arm group type: Experimental
description: injection of 1 ml intamucosal ascorbic acid 3 times with 1 week interval
arm group label: diode laser
arm group type: Experimental
description: photothermolysis by diode laser in one session
intervention type: Drug
intervention name: Ascorbic Acid 500 MG
description: ascorbic acid is vitamin that can cause gingival depigmentation
arm group label: ascorbic acid
intervention type: Device
intervention name: diode laser
description: diode laser is soft tissue laser case photothermolysis of melanoctes
arm group label: diode laser
criteria: 
gender: All
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: No
last name: Nevine H kheir ElDien, Professor
role: Study Director
affiliation: faculty of Dentistry- Ain Shams univesity
responsible party type: Principal Investigator
investigator affiliation: Ain Shams University
investigator full name: Dalia Yosri
investigator title: Assistant lecturer of oral medicine and periodontology
mesh term: Hyperpigmentation
mesh term: Ascorbic Acid