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/NCT05987384</url>
    </required_header>
    <id_info>
      <org_study_id>20220081</org_study_id>
      <nct_id>NCT05987384</nct_id>
    </id_info>
    <brief_title>The Role of Fatty Acids in Vaccine Efficacy</brief_title>
    <official_title>The Role of Fatty Acids in Vaccine Efficacy: A Randomized Controlled Clinical Trial</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Tsinghua University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Tsinghua University</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This study intends to use a randomized controlled trial design to vaccinate all participants&#xD;
        against rabies and perform ARA interventions during vaccination to test the efficacy, safety,&#xD;
        and intestinal flora of each group after immunization.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Rabies is an acute zoonotic infectious disease caused by central nervous system invasion by&#xD;
        rabies virus. At present, there is still a lack of effective treatment, and once clinical&#xD;
        symptoms appear, it is almost 100% fatal. Rabies vaccination within 24 hours of exposure may&#xD;
        reduce the incidence of rabies. Pre-exposure prophylaxis is also effective, and the current&#xD;
        recommended pre-exposure vaccination program in China is 0 days, 7th day, 21st days.&#xD;
  &#xD;
        The health of the human body is inseparable from various nutrients. There are studies&#xD;
        suggesting that arachidonic acid(ARA) has an immunomodulatory effect, but there is limited&#xD;
        evidence for its effect on vaccines. Therefore, this study will explore the effects of&#xD;
        nutritional supplements on the effectiveness of rabies vaccination.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Completed</overall_status>
    <start_date type="Actual">May 3, 2023</start_date>
    <completion_date type="Actual">July 30, 2023</completion_date>
    <primary_completion_date type="Actual">July 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>Basic Science</primary_purpose>
      <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Changes of rabies virus antibody titers</measure>
      <time_frame>Day 6, 13, 16, 19, 26 of the study</time_frame>
      <description>specific antibody titers</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Changes of neutralizing antibody titers</measure>
      <time_frame>Day 6, 13, 16, 19, 26 of the study</time_frame>
      <description>To test the ability of binding to rabies virus</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>serum blood fatty acid profiles</measure>
      <time_frame>Day 6, 13, 16，19 of the study</time_frame>
      <description>to test the change of fatty acid profiles after intervention</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>C-reactive protein</measure>
      <time_frame>Day 6, 13, 16 and 19 of the study</time_frame>
      <description>to test the potential C-reactive protein changes triggered by ARA supplementation</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Routine analysis of intestinal flora: alpha diversity</measure>
      <time_frame>Day 3 and day 19 of the study</time_frame>
      <description>The alpha diversity of microbiota in feces samples will be examined to explore the potential gut-immune response caused by intervention.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Routine analysis of intestinal flora: beta diversity</measure>
      <time_frame>Day 3 and day 19 of the study</time_frame>
      <description>The beta diversity of microbiota in feces samples will be examined to explore the potential gut-immune response caused by the intervention.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Routine analysis of intestinal flora: species abundance histogram</measure>
      <time_frame>Day 3 and day 19 of the study</time_frame>
      <description>The species abundance histogram of microbiota in feces samples will be examined to explore the potential gut-immune response caused by the intervention.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Routine analysis of intestinal flora: Lefse</measure>
      <time_frame>Day 3 and day 19 of the study</time_frame>
      <description>The Lefse of microbiota in feces samples will be conducted to explore the potential gut-immune response caused by the intervention.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Routine analysis of intestinal flora: PLS-DA</measure>
      <time_frame>Day 3 and day 19 of the study</time_frame>
      <description>The PLS-DA of microbiota in feces samples will be conducted to explore the potential gut-immune response caused by the intervention.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Routine analysis of intestinal flora: KEGG pathway</measure>
      <time_frame>Day 3 and day 19 of the study</time_frame>
      <description>The KEGG pathway microbiota in feces samples will be analyzed to explore the potential gut-immune response caused by the intervention.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Routine analysis of intestinal flora: differential KO expression</measure>
      <time_frame>Day 3 and day 19 of the study</time_frame>
      <description>The differential KO expression microbiota in feces samples will be analyzed to explore the potential gut-immune response caused by the intervention.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Macrogenomic sequencing difference of intestinal flora</measure>
      <time_frame>Day 3 and day 19 of the study</time_frame>
      <description>The macrogenomic sequencing analysis of microbiota in feces samples will be conducted to explore the potential gut-immune response caused by the intervention.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Fecal fatty acid content</measure>
      <time_frame>Day 3 and day 19 of the study</time_frame>
      <description>The fatty acid content in feces samples will be examined to explore the change of fatty acid intake caused by the intervention.</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Adverse events by ARA</measure>
      <time_frame>Day 3 to day 30 of the trial.</time_frame>
      <description>To examine the safety of using ARA, including allergy, gastrointestinal discomfort and others.</description>
    </other_outcome>
    <other_outcome>
      <measure>Serum triglyceride levels</measure>
      <time_frame>Days 3 and day 19 of the study.</time_frame>
      <description>To examine the changes of blood lipids in blood after intervention and evaluate the intervention safety. The spacific measurements include: Triglycerides (TG), high-density lipoprotein cholesterol (HDL-CHO), low-density lipoprotein cholesterol (LDL-C), and total cholesterol (TC).</description>
    </other_outcome>
    <other_outcome>
      <measure>Blood count: red blood cells</measure>
      <time_frame>tested on day 3 and day 19 of the trial.</time_frame>
      <description>To evaluate the intervention safety.</description>
    </other_outcome>
    <other_outcome>
      <measure>Blood count: white blood cells</measure>
      <time_frame>tested on day 3 and day 19 of the trial.</time_frame>
      <description>To evaluate the intervention safety.</description>
    </other_outcome>
    <other_outcome>
      <measure>Blood count: hemoglobin</measure>
      <time_frame>tested on day 3 and day 19 of the trial.</time_frame>
      <description>To evaluate the intervention safety.</description>
    </other_outcome>
    <other_outcome>
      <measure>Blood count: hematocrit</measure>
      <time_frame>tested on day 3 and day 19 of the trial.</time_frame>
      <description>To evaluate the intervention safety.</description>
    </other_outcome>
    <other_outcome>
      <measure>Blood count: platelets</measure>
      <time_frame>tested on day 3 and day 19 of the trial.</time_frame>
      <description>To evaluate the intervention safety.</description>
    </other_outcome>
    <other_outcome>
      <measure>Anxiety</measure>
      <time_frame>tested on day 13 of the trial.</time_frame>
      <description>Evaluated with General Anxiety Disorder-7 items. The scores are between 0 to 21, higher scores mean a worse outcome.</description>
    </other_outcome>
    <other_outcome>
      <measure>Depression</measure>
      <time_frame>tested on day 13 of the trial.</time_frame>
      <description>Evaluated with Patient Health Questionaire-9 items. The scores are between 0 to 27, higher scores mean a worse outcome.</description>
    </other_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Actual">45</enrollment>
    <condition>Rabies Vaccination Reaction</condition>
    <arm_group>
      <arm_group_label>Placebo group</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Sunflower oil capsules</description>
    </arm_group>
    <arm_group>
      <arm_group_label>D3 ARA group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>ARA capsules</description>
    </arm_group>
    <arm_group>
      <arm_group_label>D6 ARA group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Sunflower oil capsules and ARA capsules</description>
    </arm_group>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>Arachidonic acid</intervention_name>
      <description>D3 ARA group will receive ARA capsules from the third day of the study. D6 ARA group will receive ARA capsules from the sixth day of the study</description>
      <arm_group_label>D3 ARA group</arm_group_label>
      <arm_group_label>D6 ARA group</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>Sunflower oil</intervention_name>
      <description>The placebo group and D6 ARA group will receive sunflower oil capsules from the third day of the study. D6 ARA group will stop receiving sunflower oil capsules from the fifth day of the study.</description>
      <arm_group_label>D6 ARA group</arm_group_label>
      <arm_group_label>Placebo group</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>Rabies Vaccine (Vero Cell) for Human Use</intervention_name>
      <description>Every participant will receive three doses of rabies vaccination.</description>
      <arm_group_label>D3 ARA group</arm_group_label>
      <arm_group_label>D6 ARA group</arm_group_label>
      <arm_group_label>Placebo group</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  1）18-45 years old;&#xD;
  &#xD;
            -  2）BMI 18.5-24.9 kg/m2;&#xD;
  &#xD;
            -  3）Have not received rabies vaccination.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  1) Those who have severe disorders of abnormal lipid metabolism;&#xD;
  &#xD;
            -  2) Those who have used lipid-lowering drugs, weight loss drugs, and insulin drugs in&#xD;
               the past three months;&#xD;
  &#xD;
            -  3) Those who have received other vaccines in the past three months;&#xD;
  &#xD;
            -  4) Those who have used probiotics or prebiotics in the past three months;&#xD;
  &#xD;
            -  5) Those who have used steroids and immunosuppressants, other hormonal drugs in the&#xD;
               past year;&#xD;
  &#xD;
            -  6) Those with immunodeficiency diseases;&#xD;
  &#xD;
            -  7) Those with a history of severe vaccine allergies;&#xD;
  &#xD;
            -  8) Those who have disorders of liver and kidney metabolism;&#xD;
  &#xD;
            -  9) Those who have had fever, cold, severe diarrhea and other diseases in the past&#xD;
               month.&#xD;
  &#xD;
            -  10) Smokers in the last year.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>45 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Ai Zhao, Doctor</last_name>
      <role>Study Chair</role>
      <affiliation>Tsinghua University</affiliation>
    </overall_official>
    <location>
      <facility>
        <name>Tsinghua University</name>
        <address>
          <city>Beijing</city>
          <state>Beijing</state>
          <zip>100084</zip>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <reference>
      <citation>Shen T, Welburn SC, Sun L, Yang GJ. Progress towards dog-mediated rabies elimination in PR China: a scoping review. Infect Dis Poverty. 2023 Apr 6;12(1):30. doi: 10.1186/s40249-023-01082-3.</citation>
      <PMID>37024944</PMID>
    </reference>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>June 8, 2023</study_first_submitted>
    <study_first_submitted_qc>August 8, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 14, 2023</study_first_posted>
    <last_update_submitted>August 8, 2023</last_update_submitted>
    <last_update_submitted_qc>August 8, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 14, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Tsinghua University</investigator_affiliation>
      <investigator_full_name>Ai Zhao</investigator_full_name>
      <investigator_title>Assistant Professor</investigator_title>
    </responsible_party>
    <keyword>Rabies Vaccination</keyword>
    <keyword>Arachidonic acid</keyword>
    <keyword>efficacy</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Rabies</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <provided_document_section>
      <provided_document>
        <document_type>Study Protocol</document_type>
        <document_has_protocol>Yes</document_has_protocol>
        <document_has_icf>No</document_has_icf>
        <document_has_sap>No</document_has_sap>
        <document_date>May 20, 2023</document_date>
        <document_url>https://ClinicalTrials.gov/ProvidedDocs/84/NCT05987384/Prot_000.pdf</document_url>
      </provided_document>
      <provided_document>
        <document_type>Informed Consent Form</document_type>
        <document_has_protocol>No</document_has_protocol>
        <document_has_icf>Yes</document_has_icf>
        <document_has_sap>No</document_has_sap>
        <document_date>May 20, 2023</document_date>
        <document_url>https://ClinicalTrials.gov/ProvidedDocs/84/NCT05987384/ICF_001.pdf</document_url>
      </provided_document>
    </provided_document_section>
    <!-- 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/NCT05987384
  org study id: 20220081
  nct id: NCT05987384
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  This study intends to use a randomized controlled trial design to vaccinate all participants
        against rabies and perform ARA interventions during vaccination to test the efficacy, safety,
        and intestinal flora of each group after immunization.
  Rabies is an acute zoonotic infectious disease caused by central nervous system invasion by
        rabies virus. At present, there is still a lack of effective treatment, and once clinical
        symptoms appear, it is almost 100% fatal. Rabies vaccination within 24 hours of exposure may
        reduce the incidence of rabies. Pre-exposure prophylaxis is also effective, and the current
        recommended pre-exposure vaccination program in China is 0 days, 7th day, 21st days.
  
        The health of the human body is inseparable from various nutrients. There are studies
        suggesting that arachidonic acid(ARA) has an immunomodulatory effect, but there is limited
        evidence for its effect on vaccines. Therefore, this study will explore the effects of
        nutritional supplements on the effectiveness of rabies vaccination.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Basic Science
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  measure: Changes of rabies virus antibody titers
  time frame: Day 6, 13, 16, 19, 26 of the study
  description: specific antibody titers
  measure: Changes of neutralizing antibody titers
  time frame: Day 6, 13, 16, 19, 26 of the study
  description: To test the ability of binding to rabies virus
  measure: serum blood fatty acid profiles
  time frame: Day 6, 13, 16，19 of the study
  description: to test the change of fatty acid profiles after intervention
  measure: C-reactive protein
  time frame: Day 6, 13, 16 and 19 of the study
  description: to test the potential C-reactive protein changes triggered by ARA supplementation
  measure: Routine analysis of intestinal flora: alpha diversity
  time frame: Day 3 and day 19 of the study
  description: The alpha diversity of microbiota in feces samples will be examined to explore the potential gut-immune response caused by intervention.
  measure: Routine analysis of intestinal flora: beta diversity
  time frame: Day 3 and day 19 of the study
  description: The beta diversity of microbiota in feces samples will be examined to explore the potential gut-immune response caused by the intervention.
  measure: Routine analysis of intestinal flora: species abundance histogram
  time frame: Day 3 and day 19 of the study
  description: The species abundance histogram of microbiota in feces samples will be examined to explore the potential gut-immune response caused by the intervention.
  measure: Routine analysis of intestinal flora: Lefse
  time frame: Day 3 and day 19 of the study
  description: The Lefse of microbiota in feces samples will be conducted to explore the potential gut-immune response caused by the intervention.
  measure: Routine analysis of intestinal flora: PLS-DA
  time frame: Day 3 and day 19 of the study
  description: The PLS-DA of microbiota in feces samples will be conducted to explore the potential gut-immune response caused by the intervention.
  measure: Routine analysis of intestinal flora: KEGG pathway
  time frame: Day 3 and day 19 of the study
  description: The KEGG pathway microbiota in feces samples will be analyzed to explore the potential gut-immune response caused by the intervention.
  measure: Routine analysis of intestinal flora: differential KO expression
  time frame: Day 3 and day 19 of the study
  description: The differential KO expression microbiota in feces samples will be analyzed to explore the potential gut-immune response caused by the intervention.
  measure: Macrogenomic sequencing difference of intestinal flora
  time frame: Day 3 and day 19 of the study
  description: The macrogenomic sequencing analysis of microbiota in feces samples will be conducted to explore the potential gut-immune response caused by the intervention.
  measure: Fecal fatty acid content
  time frame: Day 3 and day 19 of the study
  description: The fatty acid content in feces samples will be examined to explore the change of fatty acid intake caused by the intervention.
  measure: Adverse events by ARA
  time frame: Day 3 to day 30 of the trial.
  description: To examine the safety of using ARA, including allergy, gastrointestinal discomfort and others.
  measure: Serum triglyceride levels
  time frame: Days 3 and day 19 of the study.
  description: To examine the changes of blood lipids in blood after intervention and evaluate the intervention safety. The spacific measurements include: Triglycerides (TG), high-density lipoprotein cholesterol (HDL-CHO), low-density lipoprotein cholesterol (LDL-C), and total cholesterol (TC).
  measure: Blood count: red blood cells
  time frame: tested on day 3 and day 19 of the trial.
  description: To evaluate the intervention safety.
  measure: Blood count: white blood cells
  time frame: tested on day 3 and day 19 of the trial.
  description: To evaluate the intervention safety.
  measure: Blood count: hemoglobin
  time frame: tested on day 3 and day 19 of the trial.
  description: To evaluate the intervention safety.
  measure: Blood count: hematocrit
  time frame: tested on day 3 and day 19 of the trial.
  description: To evaluate the intervention safety.
  measure: Blood count: platelets
  time frame: tested on day 3 and day 19 of the trial.
  description: To evaluate the intervention safety.
  measure: Anxiety
  time frame: tested on day 13 of the trial.
  description: Evaluated with General Anxiety Disorder-7 items. The scores are between 0 to 21, higher scores mean a worse outcome.
  measure: Depression
  time frame: tested on day 13 of the trial.
  description: Evaluated with Patient Health Questionaire-9 items. The scores are between 0 to 27, higher scores mean a worse outcome.
  arm group label: Placebo group
  arm group type: Placebo Comparator
  description: Sunflower oil capsules
  arm group label: D3 ARA group
  arm group type: Experimental
  description: ARA capsules
  arm group label: D6 ARA group
  arm group type: Experimental
  description: Sunflower oil capsules and ARA capsules
  intervention type: Dietary Supplement
  intervention name: Arachidonic acid
  description: D3 ARA group will receive ARA capsules from the third day of the study. D6 ARA group will receive ARA capsules from the sixth day of the study
  arm group label: D3 ARA group
  arm group label: D6 ARA group
  intervention type: Dietary Supplement
  intervention name: Sunflower oil
  description: The placebo group and D6 ARA group will receive sunflower oil capsules from the third day of the study. D6 ARA group will stop receiving sunflower oil capsules from the fifth day of the study.
  arm group label: D6 ARA group
  arm group label: Placebo group
  intervention type: Biological
  intervention name: Rabies Vaccine (Vero Cell) for Human Use
  description: Every participant will receive three doses of rabies vaccination.
  arm group label: D3 ARA group
  arm group label: D6 ARA group
  arm group label: Placebo group
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 45 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Ai Zhao, Doctor
  role: Study Chair
  affiliation: Tsinghua University
  facility: 
  country: China
  citation: Shen T, Welburn SC, Sun L, Yang GJ. Progress towards dog-mediated rabies elimination in PR China: a scoping review. Infect Dis Poverty. 2023 Apr 6;12(1):30. doi: 10.1186/s40249-023-01082-3.
  PMID: 37024944
  responsible party type: Principal Investigator
  investigator affiliation: Tsinghua University
  investigator full name: Ai Zhao
  investigator title: Assistant Professor
  mesh term: Rabies
  sharing ipd: No
  provided document: 
  provided document: 