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/NCT05963659</url>
    </required_header>
    <id_info>
      <org_study_id>20230630</org_study_id>
      <nct_id>NCT05963659</nct_id>
    </id_info>
    <brief_title>Nitrate Modulates Cognitive Impairment Via Oral Microbiota.</brief_title>
    <official_title>The Effect of Nitrate on Cognitive Function in Alcohol Dependence Patients and the Potential Microbiota Mechanism.</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Peking University Sixth Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Peking University Sixth Hospital</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>
        Alcohol use is increasingly prevalent in modern society and is known to cause cognitive&#xD;
        impairment and dysregulation of inflammatory responses. In the present study, the&#xD;
        investigators want to perform a randomised controlled trials to test whether nitrate could&#xD;
        change the oral microbiota and benefit the cognitive impairment in alcohol dependence&#xD;
        patients. The investigators survey the oral bacterial communities in saliva samples of 70&#xD;
        alcohol dependent patients following 14 days of dietary inorganic nitrate (nitrate-rich&#xD;
        beetroot juice, ~750 mg NO3- /d) and placebo (nitrate-depleted beetroot juice, ~1 mg NO3- /d)&#xD;
        supplementation.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 7, 2023</start_date>
    <completion_date type="Anticipated">August 7, 2026</completion_date>
    <primary_completion_date type="Anticipated">December 30, 2023</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>Other</primary_purpose>
      <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Changes of cognitive function from baseline to post-intervention</measure>
      <time_frame>baseline and post-intervention(two weeks after baseline test)</time_frame>
      <description>Test by Cambridge Neuropsychological Test Automatic Battery，CANTAB</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Changes of oral microbiota from baseline to post-intervention</measure>
      <time_frame>baseline and post-intervention(two weeks after baseline test)</time_frame>
      <description>Saliva samples were used to test the composition of microbiota by 16S RNA sequencing.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Changes of gut microbiota from baseline to post-intervention</measure>
      <time_frame>baseline and post-intervention(two weeks after baseline test)</time_frame>
      <description>Feces samples were used to test the composition of microbiota by 16S RNA sequencing.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Changes of nitrate and nitrite levels in serum from baseline to post-intervention</measure>
      <time_frame>baseline and post-intervention(two weeks after baseline test)</time_frame>
      <description>The collected serum samples were used to test the levels of nitrate and nitrite by High Performance Liquid Chromatography \ HPLC</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Cytokine Interleukin-1b in serum</measure>
      <time_frame>baseline and post-intervention(two weeks after baseline test)</time_frame>
      <description>The collected serum samples were used to test the levels of IL-1b by Enzyme-Linked Immunosorbent Assay</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cytokine Interleukin-6 in serum</measure>
      <time_frame>baseline and post-intervention (two weeks after baseline test)</time_frame>
      <description>The collected serum samples were used to test the levels of IL-6 by Enzyme-Linked Immunosorbent Assay</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cytokine Interleukin-10 in serum</measure>
      <time_frame>baseline and post-intervention (two weeks after baseline test)</time_frame>
      <description>The collected serum samples were used to test the levels of IL-10 by Enzyme-Linked Immunosorbent Assay</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cytokine Tumor Necrosis Factor-a in serum</measure>
      <time_frame>baseline and post-intervention(two weeks after baseline test)</time_frame>
      <description>The collected serum samples were used to test the levels of TNF-a by Enzyme-Linked Immunosorbent Assay</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The blood biochemical related parameters includes liver enzymes (alanine aminotransferase and aspartate aminotransferase)</measure>
      <time_frame>baseline and post-intervention (two weeks after baseline test)</time_frame>
      <description>The collected venous blood were sent to the department of clinical laboratory and the investigators recorded the laboratory report.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The blood biochemical related parameters blood fat (cholesterol, triglycerides, low density lipoprotein and high density lipoprotein</measure>
      <time_frame>baseline and post-intervention (two weeks after baseline test)</time_frame>
      <description>The collected venous blood were sent to the department of clinical laboratory and the investigators recorded the laboratory report.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Alcohol craving by Visual Analogue Scale（VAS）</measure>
      <time_frame>baseline and post-intervention (two weeks after baseline test)</time_frame>
      <description>Tested by Visual Analogue Scale（VAS）</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Alcohol craving</measure>
      <time_frame>baseline and post-intervention (two weeks after baseline test)</time_frame>
      <description>Tested by Tested by Penn Alcohol Craving Scale（PACS)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Alcohol withdrawal assessment</measure>
      <time_frame>baseline and post-intervention (two weeks after baseline test)</time_frame>
      <description>Tested by Clinical Institute Withdrawal Assessment of Alcohol, revised（CIWA-AR）</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Alcohol craving by Alcohol Urge Questionnaire</measure>
      <time_frame>baseline and post-intervention (two weeks after baseline test)</time_frame>
      <description>Tested by Alcohol Urge Questionnaire</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>depression</measure>
      <time_frame>baseline and post-intervention (two weeks after baseline test)</time_frame>
      <description>Test by Hamilton Depression Rating Scale</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>anxiety</measure>
      <time_frame>baseline and post-intervention(two weeks after baseline test)</time_frame>
      <description>Test by Hamilton Anxiety Rating Scale</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Sleep Quality</measure>
      <time_frame>baseline and post-intervention (two weeks after baseline test)</time_frame>
      <description>Test by pittsburgh sleep quality index</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>blood pressure</measure>
      <time_frame>baseline and post-intervention (two weeks after baseline test)</time_frame>
      <description>Test by blood pressure monitor</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">70</enrollment>
    <condition>Microtia</condition>
    <condition>Alcohol Dependence</condition>
    <arm_group>
      <arm_group_label>Group N</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>Group P</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
    </arm_group>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>nitrate-rich beetroot juice</intervention_name>
      <description>nitrate-rich beetroot juice, ~750 mg NO3- /d</description>
      <arm_group_label>Group N</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>nitrate-depleted beetroot juice</intervention_name>
      <description>nitrate-depleted beetroot juice, ~1 mg NO3- /d</description>
      <arm_group_label>Group P</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Han nationality&#xD;
  &#xD;
            2. Montreal Cognitive Assessment(MoCA) score &gt;11&#xD;
  &#xD;
            3. Diagnosis of alcohol dependence&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Past or current infectious disease&#xD;
  &#xD;
            2. Past or current heart, brain, liver, kidney, and other severe diseases&#xD;
  &#xD;
            3. Past or current metabolic diseases that can lead to abnormalities of the immune&#xD;
               system, such as obesity (Body Mass Index &gt; 30 kg/m2), diabetes, or rheumatoid&#xD;
               arthritis&#xD;
  &#xD;
            4. Past or current neurodegenerative diseases, such as Parkinson's disease&#xD;
  &#xD;
            5. Use of steroidal and non-steroidal anti-inflammatory drugs, antibiotics, antioxidants,&#xD;
               and immunosuppressive agents within two months of enrollment&#xD;
  &#xD;
            6. Use of probiotics and probiotics every day for the first two months before enrollment&#xD;
  &#xD;
            7. Previous or current DSM-IV diagnosis of schizophrenia, depression, anxiety disorder,&#xD;
               bipolar disorder, mental retardation, dementia (excluding mild cognitive impairment,&#xD;
               MCI), or substance dependence other than alcohol and nicotine&#xD;
  &#xD;
            8. Irregular eating habits that affect the oral flora (except alcohol) in the previous&#xD;
               two months&#xD;
  &#xD;
            9. Current oral disease&#xD;
        </textblock>
      </criteria>
      <gender>Male</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>60 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Hongqiang Sun</last_name>
      <role>Principal Investigator</role>
      <affiliation>Peking University Sixth Hospital</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Liangjun Pang</last_name>
      <role>Study Chair</role>
      <affiliation>Anhui mental health central</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Xiangxue li</last_name>
      <phone>+8613719234046</phone>
      <email>2011210552@bjmu.edu.cn</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>June 30, 2023</study_first_submitted>
    <study_first_submitted_qc>July 26, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">July 27, 2023</study_first_posted>
    <last_update_submitted>August 28, 2023</last_update_submitted>
    <last_update_submitted_qc>August 28, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 30, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Peking University Sixth Hospital</investigator_affiliation>
      <investigator_full_name>Hongqiang Sun</investigator_full_name>
      <investigator_title>Clinical Professor,Director</investigator_title>
    </responsible_party>
    <keyword>nitrate</keyword>
    <keyword>oral microbiota</keyword>
    <keyword>alcohol dependence</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Congenital Microtia</mesh_term>
      <mesh_term>Alcoholism</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</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/NCT05963659
  org study id: 20230630
  nct id: NCT05963659
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Alcohol use is increasingly prevalent in modern society and is known to cause cognitive
        impairment and dysregulation of inflammatory responses. In the present study, the
        investigators want to perform a randomised controlled trials to test whether nitrate could
        change the oral microbiota and benefit the cognitive impairment in alcohol dependence
        patients. The investigators survey the oral bacterial communities in saliva samples of 70
        alcohol dependent patients following 14 days of dietary inorganic nitrate (nitrate-rich
        beetroot juice, ~750 mg NO3- /d) and placebo (nitrate-depleted beetroot juice, ~1 mg NO3- /d)
        supplementation.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Other
  masking: Triple (Participant, Investigator, Outcomes Assessor)
  measure: Changes of cognitive function from baseline to post-intervention
  time frame: baseline and post-intervention(two weeks after baseline test)
  description: Test by Cambridge Neuropsychological Test Automatic Battery，CANTAB
  measure: Changes of oral microbiota from baseline to post-intervention
  time frame: baseline and post-intervention(two weeks after baseline test)
  description: Saliva samples were used to test the composition of microbiota by 16S RNA sequencing.
  measure: Changes of gut microbiota from baseline to post-intervention
  time frame: baseline and post-intervention(two weeks after baseline test)
  description: Feces samples were used to test the composition of microbiota by 16S RNA sequencing.
  measure: Changes of nitrate and nitrite levels in serum from baseline to post-intervention
  time frame: baseline and post-intervention(two weeks after baseline test)
  description: The collected serum samples were used to test the levels of nitrate and nitrite by High Performance Liquid Chromatography \ HPLC
  measure: Cytokine Interleukin-1b in serum
  time frame: baseline and post-intervention(two weeks after baseline test)
  description: The collected serum samples were used to test the levels of IL-1b by Enzyme-Linked Immunosorbent Assay
  measure: Cytokine Interleukin-6 in serum
  time frame: baseline and post-intervention (two weeks after baseline test)
  description: The collected serum samples were used to test the levels of IL-6 by Enzyme-Linked Immunosorbent Assay
  measure: Cytokine Interleukin-10 in serum
  time frame: baseline and post-intervention (two weeks after baseline test)
  description: The collected serum samples were used to test the levels of IL-10 by Enzyme-Linked Immunosorbent Assay
  measure: Cytokine Tumor Necrosis Factor-a in serum
  time frame: baseline and post-intervention(two weeks after baseline test)
  description: The collected serum samples were used to test the levels of TNF-a by Enzyme-Linked Immunosorbent Assay
  measure: The blood biochemical related parameters includes liver enzymes (alanine aminotransferase and aspartate aminotransferase)
  time frame: baseline and post-intervention (two weeks after baseline test)
  description: The collected venous blood were sent to the department of clinical laboratory and the investigators recorded the laboratory report.
  measure: The blood biochemical related parameters blood fat (cholesterol, triglycerides, low density lipoprotein and high density lipoprotein
  time frame: baseline and post-intervention (two weeks after baseline test)
  description: The collected venous blood were sent to the department of clinical laboratory and the investigators recorded the laboratory report.
  measure: Alcohol craving by Visual Analogue Scale（VAS）
  time frame: baseline and post-intervention (two weeks after baseline test)
  description: Tested by Visual Analogue Scale（VAS）
  measure: Alcohol craving
  time frame: baseline and post-intervention (two weeks after baseline test)
  description: Tested by Tested by Penn Alcohol Craving Scale（PACS)
  measure: Alcohol withdrawal assessment
  time frame: baseline and post-intervention (two weeks after baseline test)
  description: Tested by Clinical Institute Withdrawal Assessment of Alcohol, revised（CIWA-AR）
  measure: Alcohol craving by Alcohol Urge Questionnaire
  time frame: baseline and post-intervention (two weeks after baseline test)
  description: Tested by Alcohol Urge Questionnaire
  measure: depression
  time frame: baseline and post-intervention (two weeks after baseline test)
  description: Test by Hamilton Depression Rating Scale
  measure: anxiety
  time frame: baseline and post-intervention(two weeks after baseline test)
  description: Test by Hamilton Anxiety Rating Scale
  measure: Sleep Quality
  time frame: baseline and post-intervention (two weeks after baseline test)
  description: Test by pittsburgh sleep quality index
  measure: blood pressure
  time frame: baseline and post-intervention (two weeks after baseline test)
  description: Test by blood pressure monitor
  arm group label: Group N
  arm group type: Experimental
  arm group label: Group P
  arm group type: Placebo Comparator
  intervention type: Dietary Supplement
  intervention name: nitrate-rich beetroot juice
  description: nitrate-rich beetroot juice, ~750 mg NO3- /d
  arm group label: Group N
  intervention type: Dietary Supplement
  intervention name: nitrate-depleted beetroot juice
  description: nitrate-depleted beetroot juice, ~1 mg NO3- /d
  arm group label: Group P
  criteria: 
  gender: Male
  minimum age: 18 Years
  maximum age: 60 Years
  healthy volunteers: No
  last name: Hongqiang Sun
  role: Principal Investigator
  affiliation: Peking University Sixth Hospital
  last name: Liangjun Pang
  role: Study Chair
  affiliation: Anhui mental health central
  last name: Xiangxue li
  phone: +8613719234046
  email: 2011210552@bjmu.edu.cn
  responsible party type: Principal Investigator
  investigator affiliation: Peking University Sixth Hospital
  investigator full name: Hongqiang Sun
  investigator title: Clinical Professor,Director
  mesh term: Congenital Microtia
  mesh term: Alcoholism
  sharing ipd: No