xml: <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/NCT06036472</url>
    </required_header>
    <id_info>
      <org_study_id>URI 107-260623</org_study_id>
      <nct_id>NCT06036472</nct_id>
    </id_info>
    <brief_title>Impact of Periodontal Therapy on Mental Health Parameters</brief_title>
    <acronym>LeakBrainRCT</acronym>
    <official_title>Impact of Periodontal Therapy on Mental Health Parameters in Patients With Major Depression and Periodontitis: a Pilot Randomized Controlled Clinical Trial.</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Universidad Complutense de Madrid</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Ministerio de Economía y Competitividad, Spain</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Universidad Complutense de Madrid</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>
        Objectives: Primary: To determine the efficacy of periodontal treatment on mental health&#xD;
        outcomes in patients with major depression and periodontitis. Secondary: To identify the&#xD;
        effect of periodontal treatment on oral, periodontal, and fecal metagenomic microbiomes, and&#xD;
        on systemic levels of inflammation (bacterial, viral, and fungal) and their impact on mental&#xD;
        health outcomes.&#xD;
  &#xD;
        Material and method:&#xD;
  &#xD;
        A 6-month pilot randomized controlled clinical trial is designed. The study will be conducted&#xD;
        in patients with moderate or severe DM (Patient Health Questionnaire-9 [PHQ-9] index of 9 or&#xD;
        higher) and stage III-IV periodontitis who will be assigned to two different interventions:&#xD;
  &#xD;
          -  Test group: standard periodontal treatment consisting of two sessions of supragingival&#xD;
             and subgingival debridement (steps 1 and 2) under local anesthesia.&#xD;
  &#xD;
          -  Control group: periodontal treatment consisting of two sessions of supragingival&#xD;
             debridement (step 1) under local anesthesia.&#xD;
  &#xD;
        The study will consist of 6 visits:&#xD;
  &#xD;
          -  Screening visit (v0)&#xD;
  &#xD;
          -  Baseline visit (v1):&#xD;
  &#xD;
               -  In the mental health center: patients will receive a structured clinical interview&#xD;
                  for the DSM-IV (SCID) and the patient will fill out a series of specific scales on&#xD;
                  a study-specific electronic device [Beck Depression Inventory (BDI); UCLA&#xD;
                  Loneliness Scale, Center for Epidemiologic Studies Depression scale [CES-D];&#xD;
                  Childhood Trauma Questionnaire short form (CTQ-SF); The World Health Organization&#xD;
                  Quality of Life questionnaire (WHOQOL); Hamilton scale (HAM-D17); Global Assessment&#xD;
                  of Functioning (GAF) Scale].&#xD;
  &#xD;
               -  At the UCM School of Dentistry: patients will receive a complete periodontal&#xD;
                  examination (clinical and radiographic). A subgingival microbiological sample, a&#xD;
                  saliva sample and a blood sample will also be taken.&#xD;
  &#xD;
               -  At the participant's home: the stool samples will be deposited by the participants&#xD;
                  at home in the specific collection vial.&#xD;
  &#xD;
          -  Intervention visits (v2-3): Two periodontal treatment sessions (test or control) will be&#xD;
             carried out one week apart.&#xD;
  &#xD;
          -  Re-evaluation visit (v4): Six weeks after treatment, all periodontal clinical variables&#xD;
             will be recorded.&#xD;
  &#xD;
          -  Follow-up visits at 3 and 6 months: after periodontal treatment, all the variables&#xD;
             recorded at the baseline visit will be taken&#xD;
  &#xD;
        Statistical analysis:&#xD;
  &#xD;
        Periodontal treatment (test/control) will be considered as the independent variable and the&#xD;
        Hamilton scale (HAM-D17) will be considered the primary response variable. The rest of the&#xD;
        variables will be considered as secondary variables. A crude bivariate analysis of comparison&#xD;
        of means or proportions will be carried out depending on the nature of the variable. In&#xD;
        addition, crude and adjusted regression models will be performed.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 2023</start_date>
    <completion_date type="Anticipated">December 2025</completion_date>
    <primary_completion_date type="Anticipated">December 2025</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>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Hamilton scale (HAM-D17)</measure>
      <time_frame>Baseline</time_frame>
      <description>Range: 0 to 52. The higher the score, the more severethe depressive symptoms</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Hamilton scale (HAM-D17)</measure>
      <time_frame>3 months</time_frame>
      <description>Range: 0 to 52. The higher the score, the more severethe depressive symptoms</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Hamilton scale (HAM-D17)</measure>
      <time_frame>6 months</time_frame>
      <description>Range: 0 to 52. The higher the score, the more severethe depressive symptoms</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Childhood Trauma Questionnaire short form (CTQ-SF)</measure>
      <time_frame>Baseline</time_frame>
      <description>Range: 25 to 125. A higherscore means more (and worst) traumatic experience</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Childhood Trauma Questionnaire short form (CTQ-SF)</measure>
      <time_frame>3 months</time_frame>
      <description>Range: 25 to 125. A higherscore means more (and worst) traumatic experience</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Childhood Trauma Questionnaire short form (CTQ-SF)</measure>
      <time_frame>6 months</time_frame>
      <description>Range: 25 to 125. A higherscore means more (and worst) traumatic experience</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>UCLA Loneliness Scale (Spanish version)</measure>
      <time_frame>Baseline</time_frame>
      <description>Range: 20 to 80. Higher scores indicatehigher levels of loneliness</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>UCLA Loneliness Scale (Spanish version)</measure>
      <time_frame>3 months</time_frame>
      <description>Range: 20 to 80. Higher scores indicatehigher levels of loneliness</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>UCLA Loneliness Scale (Spanish version)</measure>
      <time_frame>6 months</time_frame>
      <description>Range: 20 to 80. Higher scores indicatehigher levels of loneliness</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The World Health Organization Quality of Life questionnaire (WHOQOL)</measure>
      <time_frame>Baseline</time_frame>
      <description>Range: o to100. A higher score means better quality of life.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The World Health Organization Quality of Life questionnaire (WHOQOL)</measure>
      <time_frame>3 months</time_frame>
      <description>Range: o to100. A higher score means better quality of life.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The World Health Organization Quality of Life questionnaire (WHOQOL)</measure>
      <time_frame>6 months</time_frame>
      <description>Range: o to100. A higher score means better quality of life.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Beck Depression Inventory (BDI)</measure>
      <time_frame>Baseline</time_frame>
      <description>Range: 0 to 63. A higher score means more severe-depressive symptomatology</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Beck Depression Inventory (BDI)</measure>
      <time_frame>3 months</time_frame>
      <description>Range: 0 to 63. A higher score means more severe-depressive symptomatology</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Beck Depression Inventory (BDI)</measure>
      <time_frame>6 months</time_frame>
      <description>Range: 0 to 63. A higher score means more severe-depressive symptomatology</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Centre for Epidemiologic Studies Depression scale [CES-D]</measure>
      <time_frame>Baseline</time_frame>
      <description>Range: 0 to 60. Higher scores indicate the presence of more severe symptomatology</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Centre for Epidemiologic Studies Depression scale [CES-D]</measure>
      <time_frame>3 months</time_frame>
      <description>Range: 0 to 60. Higher scores indicate the presence of more severe symptomatology</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Centre for Epidemiologic Studies Depression scale [CES-D]</measure>
      <time_frame>6 months</time_frame>
      <description>Range: 0 to 60. Higher scores indicate the presence of more severe symptomatology</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Global Assessment of Functioning (GAF) Scale</measure>
      <time_frame>Baseline</time_frame>
      <description>Range: 1 to 100. A higher scoremeans better functioning. A score of 0 means Inadequate information.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Global Assessment of Functioning (GAF) Scale</measure>
      <time_frame>3 months</time_frame>
      <description>Range: 1 to 100. A higher scoremeans better functioning. A score of 0 means Inadequate information.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Global Assessment of Functioning (GAF) Scale</measure>
      <time_frame>6 months</time_frame>
      <description>Range: 1 to 100. A higher scoremeans better functioning. A score of 0 means Inadequate information.</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Plaque index</measure>
      <time_frame>Baseline</time_frame>
      <description>presence/absence</description>
    </other_outcome>
    <other_outcome>
      <measure>Plaque index</measure>
      <time_frame>3 months</time_frame>
      <description>presence/absence</description>
    </other_outcome>
    <other_outcome>
      <measure>Plaque index</measure>
      <time_frame>6 months</time_frame>
      <description>presence/absence</description>
    </other_outcome>
    <other_outcome>
      <measure>Bleeding on probing</measure>
      <time_frame>Baseline</time_frame>
      <description>Assessed dichotomously within 15 seconds after probing</description>
    </other_outcome>
    <other_outcome>
      <measure>Bleeding on probing</measure>
      <time_frame>3 months</time_frame>
      <description>Assessed dichotomously within 15 seconds after probing</description>
    </other_outcome>
    <other_outcome>
      <measure>Bleeding on probing</measure>
      <time_frame>6 months</time_frame>
      <description>Assessed dichotomously within 15 seconds after probing</description>
    </other_outcome>
    <other_outcome>
      <measure>Suppuration on probing</measure>
      <time_frame>Baseline</time_frame>
      <description>Assessed dichotomously post-probing</description>
    </other_outcome>
    <other_outcome>
      <measure>Suppuration on probing</measure>
      <time_frame>3 months</time_frame>
      <description>Assessed dichotomously post-probing</description>
    </other_outcome>
    <other_outcome>
      <measure>Suppuration on probing</measure>
      <time_frame>6 months</time_frame>
      <description>Assessed dichotomously post-probing</description>
    </other_outcome>
    <other_outcome>
      <measure>Probing depth</measure>
      <time_frame>Baseline</time_frame>
      <description>Defined as the distance in mm between the bottom of the pocket and the gingival margin</description>
    </other_outcome>
    <other_outcome>
      <measure>Probing depth</measure>
      <time_frame>3 months</time_frame>
      <description>Defined as the distance in mm between the bottom of the pocket and the gingival margin</description>
    </other_outcome>
    <other_outcome>
      <measure>Probing depth</measure>
      <time_frame>6 months</time_frame>
      <description>Defined as the distance in mm between the bottom of the pocket and the gingival margin</description>
    </other_outcome>
    <other_outcome>
      <measure>Recession</measure>
      <time_frame>Baseline</time_frame>
      <description>defined as the distance in mm between the amelocemental boundary and the gingival margin.</description>
    </other_outcome>
    <other_outcome>
      <measure>Recession</measure>
      <time_frame>3 months</time_frame>
      <description>defined as the distance in mm between the amelocemental boundary and the gingival margin.</description>
    </other_outcome>
    <other_outcome>
      <measure>Recession</measure>
      <time_frame>6 months</time_frame>
      <description>defined as the distance in mm between the amelocemental boundary and the gingival margin.</description>
    </other_outcome>
    <other_outcome>
      <measure>Number of teeth lost</measure>
      <time_frame>Baseline</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>Number of teeth lost</measure>
      <time_frame>3 months</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>Number of teeth lost</measure>
      <time_frame>6 months</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>Microbiological outcomes</measure>
      <time_frame>Baseline</time_frame>
      <description>Subgingival biofilm samples will be taken from samples of gingival crevicular fluid. DNA samples will be frozen at -20°C and preserved until further analysis by quantitative polymerase chain reaction (q-PCR) and 16S rRNA sequencing, using the Illumina MiSeq platform</description>
    </other_outcome>
    <other_outcome>
      <measure>Microbiological outcomes</measure>
      <time_frame>3 months</time_frame>
      <description>Subgingival biofilm samples will be taken from samples of gingival crevicular fluid. DNA samples will be frozen at -20°C and preserved until further analysis by quantitative polymerase chain reaction (q-PCR) (Marín et al., 2019) and 16S rRNA sequencing, using the Illumina MiSeq platform</description>
    </other_outcome>
    <other_outcome>
      <measure>Microbiological outcomes</measure>
      <time_frame>6 months</time_frame>
      <description>Subgingival biofilm samples will be taken from samples of gingival crevicular fluid. DNA samples will be frozen at -20°C and preserved until further analysis by quantitative polymerase chain reaction (q-PCR) (Marín et al., 2019) and 16S rRNA sequencing, using the Illumina MiSeq platform</description>
    </other_outcome>
    <other_outcome>
      <measure>Plasma levels of inflammatory mediators</measure>
      <time_frame>Baseline</time_frame>
      <description>Interleukin-1β, Tumor Necrosis Factor-α, prostaglandin-E2, C reactive protein, D-Lactate and intestinal-type fatty acid binding protein 2 [FABP2]), lipopolysaccharide (LPS). matrix metalloproteinase (MMP)-9 levels, S-100B protein levels, quinolinic acid levels, and the ratio between kynurenic and quinolinic acid</description>
    </other_outcome>
    <other_outcome>
      <measure>Plasma levels of inflammatory mediators</measure>
      <time_frame>3 months</time_frame>
      <description>Interleukin-1β, Tumor Necrosis Factor-α, prostaglandin-E2, C reactive protein, D-Lactate and intestinal-type fatty acid binding protein 2 [FABP2]), lipopolysaccharide (LPS). matrix metalloproteinase (MMP)-9 levels, S-100B protein levels, quinolinic acid levels, and the ratio between kynurenic and quinolinic acid</description>
    </other_outcome>
    <other_outcome>
      <measure>Plasma levels of inflammatory mediators</measure>
      <time_frame>6 months</time_frame>
      <description>Interleukin-1β, Tumor Necrosis Factor-α, prostaglandin-E2, C reactive protein, D-Lactate and intestinal-type fatty acid binding protein 2 [FABP2]), lipopolysaccharide (LPS). matrix metalloproteinase (MMP)-9 levels, S-100B protein levels, quinolinic acid levels, and the ratio between kynurenic and quinolinic acid</description>
    </other_outcome>
    <other_outcome>
      <measure>Saliva samples</measure>
      <time_frame>Baseline</time_frame>
      <description>Oral microbial DNA will be used for library preparation and metagenomic shotgun sequencing using the Illumina HiSeq 2500 System. Shotgun metagenomic sequencing can identify bacteria, fungi, and viruses, with a resolution that allows species-level identification. Sequences will be compared to phylogenetic and functional databases to obtain taxonomic and functional profiles.</description>
    </other_outcome>
    <other_outcome>
      <measure>Saliva samples</measure>
      <time_frame>3 months</time_frame>
      <description>Oral microbial DNA will be used for library preparation and metagenomic shotgun sequencing using the Illumina HiSeq 2500 System. Shotgun metagenomic sequencing can identify bacteria, fungi, and viruses, with a resolution that allows species-level identification. Sequences will be compared to phylogenetic and functional databases to obtain taxonomic and functional profiles.</description>
    </other_outcome>
    <other_outcome>
      <measure>Saliva samples</measure>
      <time_frame>6 months</time_frame>
      <description>Oral microbial DNA will be used for library preparation and metagenomic shotgun sequencing using the Illumina HiSeq 2500 System. Shotgun metagenomic sequencing can identify bacteria, fungi, and viruses, with a resolution that allows species-level identification. Sequences will be compared to phylogenetic and functional databases to obtain taxonomic and functional profiles.</description>
    </other_outcome>
    <other_outcome>
      <measure>Stool samples</measure>
      <time_frame>Baseline</time_frame>
      <description>Gut microbial DNA will be used for library preparation and metagenomic shotgun sequencing using the Illumina HiSeq 2500 System. Shotgun metagenomic sequencing can identify bacteria, fungi, and viruses, with a resolution that allows species-level identification. Sequences will be compared to phylogenetic and functional databases to obtain taxonomic and functional profiles.</description>
    </other_outcome>
    <other_outcome>
      <measure>Stool samples</measure>
      <time_frame>3 months</time_frame>
      <description>Gut microbial DNA will be used for library preparation and metagenomic shotgun sequencing using the Illumina HiSeq 2500 System. Shotgun metagenomic sequencing can identify bacteria, fungi, and viruses, with a resolution that allows species-level identification. Sequences will be compared to phylogenetic and functional databases to obtain taxonomic and functional profiles.</description>
    </other_outcome>
    <other_outcome>
      <measure>Stool samples</measure>
      <time_frame>6 months</time_frame>
      <description>Gut microbial DNA will be used for library preparation and metagenomic shotgun sequencing using the Illumina HiSeq 2500 System. Shotgun metagenomic sequencing can identify bacteria, fungi, and viruses, with a resolution that allows species-level identification. Sequences will be compared to phylogenetic and functional databases to obtain taxonomic and functional profiles.</description>
    </other_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">40</enrollment>
    <condition>Periodontitis</condition>
    <condition>Depression</condition>
    <arm_group>
      <arm_group_label>Subgingival therapy</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participant will receive standard periodontal treatment consisting of two sessions of supra- and subgingival debridement (steps 1 and 2) under local anesthesia following current guidelines for periodontal therapy in patients with periodontitis (Herrera et al., 2022; Sanz et al., 2020). The use of chlorhexidine (0.12%) and cetylpyridinium chloride (0.05%) mouthwash will be prescribed twice a day for 15 days (Perio-Aid®, Dentaid, Barcelona, Spain). If needed, hopeless teeth might be extracted during this step.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Supragingival therapy</arm_group_label>
      <arm_group_type>Other</arm_group_type>
      <description>Periodontal treatment consisting of two sessions of supragingival debridement with anesthesia (step 1) and administration of a placebo mouthwash (FluorAid®, Dentaid, Barcelona, Spain), twice a day for 15 days.</description>
    </arm_group>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Standard periodontal therapy (steps 1 &amp; 2)</intervention_name>
      <description>participant will receive standard periodontal treatment consisting of two sessions of supra- and subgingival debridement (steps 1 and 2) under local anesthesia following current guidelines for periodontal therapy in patients with periodontitis (Herrera et al., 2022; Sanz et al., 2020). The use of chlorhexidine (0.12%) and cetylpyridinium chloride (0.05%) mouthwash will be prescribed twice a day for 15 days (Perio-Aid®, Dentaid, Barcelona, Spain). If needed, hopeless teeth might be extracted during this step.</description>
      <arm_group_label>Subgingival therapy</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>supragingival debridement with anesthesia (step 1)</intervention_name>
      <description>periodontal treatment consisting of two sessions of supragingival debridement with anesthesia (step 1) and administration of a placebo mouthwash (FluorAid®, Dentaid, Barcelona, Spain), twice a day for 15 days.</description>
      <arm_group_label>Supragingival therapy</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          5.3.1. Inclusion criteria:&#xD;
  &#xD;
            -  Age greater or equal to 18 years.&#xD;
  &#xD;
            -  Patients with moderate or severe major depression, without severe suicide ideation, as&#xD;
               characterized by the Patient Health Questionnaire (PHQ)-9 index (values of 9 or&#xD;
               greater) and by the Structured Clinical Interview for DSM-5 - (SCID) will be selected.&#xD;
  &#xD;
            -  Subjects with periodontitis stages III or IV, according to the 2018 Classification on&#xD;
               periodontal and peri-implant diseases (Papapanou et al., 2018).&#xD;
  &#xD;
          5.3.2. Exclusion criteria:&#xD;
  &#xD;
            -  Pregnant or breastfeeding women.&#xD;
  &#xD;
            -  Diabetes mellitus.&#xD;
  &#xD;
            -  Chronic conditions: HIV infection, chronic intake of NSAIDs.&#xD;
  &#xD;
            -  Comorbidity with other mental disorders: eating disorders, borderline personality&#xD;
               disorders, bipolar disorders, schizophrenia and related disorders, and/or any mental&#xD;
               serious disease other than major depression.&#xD;
  &#xD;
            -  Severe suicide ideation.&#xD;
  &#xD;
            -  Smokers of 10 or more cigarettes per day.&#xD;
  &#xD;
            -  Patients who had received periodontal treatment for periodontitis in the last year.&#xD;
  &#xD;
            -  Presence of necrotizing periodontal diseases.&#xD;
  &#xD;
            -  Presence of less than 3 teeth per quadrant.&#xD;
  &#xD;
            -  Antibiotic use in the last 6 months prior to the study.&#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_contact>
      <last_name>Elena Figuero, Prof.</last_name>
      <phone>0034913942186</phone>
      <email>elfiguer@ucm.es</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Juan Carlos Leza Cerro, Prof.</last_name>
      <phone>0034913941478</phone>
      <email>jcleza@ucm.es</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Faculty of Dentistry, University Complutense of Madrid (UCM)</name>
        <address>
          <city>Madrid</city>
          <zip>28034</zip>
          <country>Spain</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Instituto de Psiquiatría y Salud Mental, Hospital Clínico San Carlos</name>
        <address>
          <city>Madrid</city>
          <zip>28040</zip>
          <country>Spain</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>Spain</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 26, 2023</study_first_submitted>
    <study_first_submitted_qc>September 6, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 14, 2023</study_first_posted>
    <last_update_submitted>September 6, 2023</last_update_submitted>
    <last_update_submitted_qc>September 6, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 14, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Periodontitis</mesh_term>
      <mesh_term>Depression</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Anesthetics</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06036472
  org study id: URI 107-260623
  nct id: NCT06036472
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Objectives: Primary: To determine the efficacy of periodontal treatment on mental health
        outcomes in patients with major depression and periodontitis. Secondary: To identify the
        effect of periodontal treatment on oral, periodontal, and fecal metagenomic microbiomes, and
        on systemic levels of inflammation (bacterial, viral, and fungal) and their impact on mental
        health outcomes.
  
        Material and method:
  
        A 6-month pilot randomized controlled clinical trial is designed. The study will be conducted
        in patients with moderate or severe DM (Patient Health Questionnaire-9 [PHQ-9] index of 9 or
        higher) and stage III-IV periodontitis who will be assigned to two different interventions:
  
          -  Test group: standard periodontal treatment consisting of two sessions of supragingival
             and subgingival debridement (steps 1 and 2) under local anesthesia.
  
          -  Control group: periodontal treatment consisting of two sessions of supragingival
             debridement (step 1) under local anesthesia.
  
        The study will consist of 6 visits:
  
          -  Screening visit (v0)
  
          -  Baseline visit (v1):
  
               -  In the mental health center: patients will receive a structured clinical interview
                  for the DSM-IV (SCID) and the patient will fill out a series of specific scales on
                  a study-specific electronic device [Beck Depression Inventory (BDI); UCLA
                  Loneliness Scale, Center for Epidemiologic Studies Depression scale [CES-D];
                  Childhood Trauma Questionnaire short form (CTQ-SF); The World Health Organization
                  Quality of Life questionnaire (WHOQOL); Hamilton scale (HAM-D17); Global Assessment
                  of Functioning (GAF) Scale].
  
               -  At the UCM School of Dentistry: patients will receive a complete periodontal
                  examination (clinical and radiographic). A subgingival microbiological sample, a
                  saliva sample and a blood sample will also be taken.
  
               -  At the participant's home: the stool samples will be deposited by the participants
                  at home in the specific collection vial.
  
          -  Intervention visits (v2-3): Two periodontal treatment sessions (test or control) will be
             carried out one week apart.
  
          -  Re-evaluation visit (v4): Six weeks after treatment, all periodontal clinical variables
             will be recorded.
  
          -  Follow-up visits at 3 and 6 months: after periodontal treatment, all the variables
             recorded at the baseline visit will be taken
  
        Statistical analysis:
  
        Periodontal treatment (test/control) will be considered as the independent variable and the
        Hamilton scale (HAM-D17) will be considered the primary response variable. The rest of the
        variables will be considered as secondary variables. A crude bivariate analysis of comparison
        of means or proportions will be carried out depending on the nature of the variable. In
        addition, crude and adjusted regression models will be performed.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Triple (Participant, Investigator, Outcomes Assessor)
  measure: Hamilton scale (HAM-D17)
  time frame: Baseline
  description: Range: 0 to 52. The higher the score, the more severethe depressive symptoms
  measure: Hamilton scale (HAM-D17)
  time frame: 3 months
  description: Range: 0 to 52. The higher the score, the more severethe depressive symptoms
  measure: Hamilton scale (HAM-D17)
  time frame: 6 months
  description: Range: 0 to 52. The higher the score, the more severethe depressive symptoms
  measure: Childhood Trauma Questionnaire short form (CTQ-SF)
  time frame: Baseline
  description: Range: 25 to 125. A higherscore means more (and worst) traumatic experience
  measure: Childhood Trauma Questionnaire short form (CTQ-SF)
  time frame: 3 months
  description: Range: 25 to 125. A higherscore means more (and worst) traumatic experience
  measure: Childhood Trauma Questionnaire short form (CTQ-SF)
  time frame: 6 months
  description: Range: 25 to 125. A higherscore means more (and worst) traumatic experience
  measure: UCLA Loneliness Scale (Spanish version)
  time frame: Baseline
  description: Range: 20 to 80. Higher scores indicatehigher levels of loneliness
  measure: UCLA Loneliness Scale (Spanish version)
  time frame: 3 months
  description: Range: 20 to 80. Higher scores indicatehigher levels of loneliness
  measure: UCLA Loneliness Scale (Spanish version)
  time frame: 6 months
  description: Range: 20 to 80. Higher scores indicatehigher levels of loneliness
  measure: The World Health Organization Quality of Life questionnaire (WHOQOL)
  time frame: Baseline
  description: Range: o to100. A higher score means better quality of life.
  measure: The World Health Organization Quality of Life questionnaire (WHOQOL)
  time frame: 3 months
  description: Range: o to100. A higher score means better quality of life.
  measure: The World Health Organization Quality of Life questionnaire (WHOQOL)
  time frame: 6 months
  description: Range: o to100. A higher score means better quality of life.
  measure: Beck Depression Inventory (BDI)
  time frame: Baseline
  description: Range: 0 to 63. A higher score means more severe-depressive symptomatology
  measure: Beck Depression Inventory (BDI)
  time frame: 3 months
  description: Range: 0 to 63. A higher score means more severe-depressive symptomatology
  measure: Beck Depression Inventory (BDI)
  time frame: 6 months
  description: Range: 0 to 63. A higher score means more severe-depressive symptomatology
  measure: Centre for Epidemiologic Studies Depression scale [CES-D]
  time frame: Baseline
  description: Range: 0 to 60. Higher scores indicate the presence of more severe symptomatology
  measure: Centre for Epidemiologic Studies Depression scale [CES-D]
  time frame: 3 months
  description: Range: 0 to 60. Higher scores indicate the presence of more severe symptomatology
  measure: Centre for Epidemiologic Studies Depression scale [CES-D]
  time frame: 6 months
  description: Range: 0 to 60. Higher scores indicate the presence of more severe symptomatology
  measure: Global Assessment of Functioning (GAF) Scale
  time frame: Baseline
  description: Range: 1 to 100. A higher scoremeans better functioning. A score of 0 means Inadequate information.
  measure: Global Assessment of Functioning (GAF) Scale
  time frame: 3 months
  description: Range: 1 to 100. A higher scoremeans better functioning. A score of 0 means Inadequate information.
  measure: Global Assessment of Functioning (GAF) Scale
  time frame: 6 months
  description: Range: 1 to 100. A higher scoremeans better functioning. A score of 0 means Inadequate information.
  measure: Plaque index
  time frame: Baseline
  description: presence/absence
  measure: Plaque index
  time frame: 3 months
  description: presence/absence
  measure: Plaque index
  time frame: 6 months
  description: presence/absence
  measure: Bleeding on probing
  time frame: Baseline
  description: Assessed dichotomously within 15 seconds after probing
  measure: Bleeding on probing
  time frame: 3 months
  description: Assessed dichotomously within 15 seconds after probing
  measure: Bleeding on probing
  time frame: 6 months
  description: Assessed dichotomously within 15 seconds after probing
  measure: Suppuration on probing
  time frame: Baseline
  description: Assessed dichotomously post-probing
  measure: Suppuration on probing
  time frame: 3 months
  description: Assessed dichotomously post-probing
  measure: Suppuration on probing
  time frame: 6 months
  description: Assessed dichotomously post-probing
  measure: Probing depth
  time frame: Baseline
  description: Defined as the distance in mm between the bottom of the pocket and the gingival margin
  measure: Probing depth
  time frame: 3 months
  description: Defined as the distance in mm between the bottom of the pocket and the gingival margin
  measure: Probing depth
  time frame: 6 months
  description: Defined as the distance in mm between the bottom of the pocket and the gingival margin
  measure: Recession
  time frame: Baseline
  description: defined as the distance in mm between the amelocemental boundary and the gingival margin.
  measure: Recession
  time frame: 3 months
  description: defined as the distance in mm between the amelocemental boundary and the gingival margin.
  measure: Recession
  time frame: 6 months
  description: defined as the distance in mm between the amelocemental boundary and the gingival margin.
  measure: Number of teeth lost
  time frame: Baseline
  measure: Number of teeth lost
  time frame: 3 months
  measure: Number of teeth lost
  time frame: 6 months
  measure: Microbiological outcomes
  time frame: Baseline
  description: Subgingival biofilm samples will be taken from samples of gingival crevicular fluid. DNA samples will be frozen at -20°C and preserved until further analysis by quantitative polymerase chain reaction (q-PCR) and 16S rRNA sequencing, using the Illumina MiSeq platform
  measure: Microbiological outcomes
  time frame: 3 months
  description: Subgingival biofilm samples will be taken from samples of gingival crevicular fluid. DNA samples will be frozen at -20°C and preserved until further analysis by quantitative polymerase chain reaction (q-PCR) (Marín et al., 2019) and 16S rRNA sequencing, using the Illumina MiSeq platform
  measure: Microbiological outcomes
  time frame: 6 months
  description: Subgingival biofilm samples will be taken from samples of gingival crevicular fluid. DNA samples will be frozen at -20°C and preserved until further analysis by quantitative polymerase chain reaction (q-PCR) (Marín et al., 2019) and 16S rRNA sequencing, using the Illumina MiSeq platform
  measure: Plasma levels of inflammatory mediators
  time frame: Baseline
  description: Interleukin-1β, Tumor Necrosis Factor-α, prostaglandin-E2, C reactive protein, D-Lactate and intestinal-type fatty acid binding protein 2 [FABP2]), lipopolysaccharide (LPS). matrix metalloproteinase (MMP)-9 levels, S-100B protein levels, quinolinic acid levels, and the ratio between kynurenic and quinolinic acid
  measure: Plasma levels of inflammatory mediators
  time frame: 3 months
  description: Interleukin-1β, Tumor Necrosis Factor-α, prostaglandin-E2, C reactive protein, D-Lactate and intestinal-type fatty acid binding protein 2 [FABP2]), lipopolysaccharide (LPS). matrix metalloproteinase (MMP)-9 levels, S-100B protein levels, quinolinic acid levels, and the ratio between kynurenic and quinolinic acid
  measure: Plasma levels of inflammatory mediators
  time frame: 6 months
  description: Interleukin-1β, Tumor Necrosis Factor-α, prostaglandin-E2, C reactive protein, D-Lactate and intestinal-type fatty acid binding protein 2 [FABP2]), lipopolysaccharide (LPS). matrix metalloproteinase (MMP)-9 levels, S-100B protein levels, quinolinic acid levels, and the ratio between kynurenic and quinolinic acid
  measure: Saliva samples
  time frame: Baseline
  description: Oral microbial DNA will be used for library preparation and metagenomic shotgun sequencing using the Illumina HiSeq 2500 System. Shotgun metagenomic sequencing can identify bacteria, fungi, and viruses, with a resolution that allows species-level identification. Sequences will be compared to phylogenetic and functional databases to obtain taxonomic and functional profiles.
  measure: Saliva samples
  time frame: 3 months
  description: Oral microbial DNA will be used for library preparation and metagenomic shotgun sequencing using the Illumina HiSeq 2500 System. Shotgun metagenomic sequencing can identify bacteria, fungi, and viruses, with a resolution that allows species-level identification. Sequences will be compared to phylogenetic and functional databases to obtain taxonomic and functional profiles.
  measure: Saliva samples
  time frame: 6 months
  description: Oral microbial DNA will be used for library preparation and metagenomic shotgun sequencing using the Illumina HiSeq 2500 System. Shotgun metagenomic sequencing can identify bacteria, fungi, and viruses, with a resolution that allows species-level identification. Sequences will be compared to phylogenetic and functional databases to obtain taxonomic and functional profiles.
  measure: Stool samples
  time frame: Baseline
  description: Gut microbial DNA will be used for library preparation and metagenomic shotgun sequencing using the Illumina HiSeq 2500 System. Shotgun metagenomic sequencing can identify bacteria, fungi, and viruses, with a resolution that allows species-level identification. Sequences will be compared to phylogenetic and functional databases to obtain taxonomic and functional profiles.
  measure: Stool samples
  time frame: 3 months
  description: Gut microbial DNA will be used for library preparation and metagenomic shotgun sequencing using the Illumina HiSeq 2500 System. Shotgun metagenomic sequencing can identify bacteria, fungi, and viruses, with a resolution that allows species-level identification. Sequences will be compared to phylogenetic and functional databases to obtain taxonomic and functional profiles.
  measure: Stool samples
  time frame: 6 months
  description: Gut microbial DNA will be used for library preparation and metagenomic shotgun sequencing using the Illumina HiSeq 2500 System. Shotgun metagenomic sequencing can identify bacteria, fungi, and viruses, with a resolution that allows species-level identification. Sequences will be compared to phylogenetic and functional databases to obtain taxonomic and functional profiles.
  arm group label: Subgingival therapy
  arm group type: Experimental
  description: Participant will receive standard periodontal treatment consisting of two sessions of supra- and subgingival debridement (steps 1 and 2) under local anesthesia following current guidelines for periodontal therapy in patients with periodontitis (Herrera et al., 2022; Sanz et al., 2020). The use of chlorhexidine (0.12%) and cetylpyridinium chloride (0.05%) mouthwash will be prescribed twice a day for 15 days (Perio-Aid®, Dentaid, Barcelona, Spain). If needed, hopeless teeth might be extracted during this step.
  arm group label: Supragingival therapy
  arm group type: Other
  description: Periodontal treatment consisting of two sessions of supragingival debridement with anesthesia (step 1) and administration of a placebo mouthwash (FluorAid®, Dentaid, Barcelona, Spain), twice a day for 15 days.
  intervention type: Procedure
  intervention name: Standard periodontal therapy (steps 1 & 2)
  description: participant will receive standard periodontal treatment consisting of two sessions of supra- and subgingival debridement (steps 1 and 2) under local anesthesia following current guidelines for periodontal therapy in patients with periodontitis (Herrera et al., 2022; Sanz et al., 2020). The use of chlorhexidine (0.12%) and cetylpyridinium chloride (0.05%) mouthwash will be prescribed twice a day for 15 days (Perio-Aid®, Dentaid, Barcelona, Spain). If needed, hopeless teeth might be extracted during this step.
  arm group label: Subgingival therapy
  intervention type: Procedure
  intervention name: supragingival debridement with anesthesia (step 1)
  description: periodontal treatment consisting of two sessions of supragingival debridement with anesthesia (step 1) and administration of a placebo mouthwash (FluorAid®, Dentaid, Barcelona, Spain), twice a day for 15 days.
  arm group label: Supragingival therapy
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Elena Figuero, Prof.
  phone: 0034913942186
  email: elfiguer@ucm.es
  last name: Juan Carlos Leza Cerro, Prof.
  phone: 0034913941478
  email: jcleza@ucm.es
  facility: 
  facility: 
  country: Spain
  responsible party type: Sponsor
  mesh term: Periodontitis
  mesh term: Depression
  mesh term: Anesthetics
  sharing ipd: Undecided