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/NCT06024096</url>
    </required_header>
    <id_info>
      <org_study_id>STUDY00006239</org_study_id>
      <nct_id>NCT06024096</nct_id>
    </id_info>
    <brief_title>Systems Biological Assessment of Statin Effect on Vaccine Responses</brief_title>
    <official_title>Systems Biological Assessment of Statin Effect on Vaccine Responses</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Emory University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Emory University</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>Yes</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        This study is being done to answer the question: Does the use of statin lipid-lowering&#xD;
        medication change the effect of influenza vaccine? The research team will use the knowledge&#xD;
        gained from answering this question to understand how this medication affects long-lasting&#xD;
        immune responses to vaccines. The researchers will study the immune response to the influenza&#xD;
        vaccine in the blood (where antibodies are). The team will also look at how statin therapy&#xD;
        affects the bacteria that live in the gut by collecting stool samples. To be in this&#xD;
        research, participants must be adults willing to receive vaccines.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Statins are widely used for their lipid-lowering and cardiovascular protective effects.&#xD;
        Additional research has shown that statins can be anti-inflammatory and play a part in&#xD;
        modulating the immune system. These effects are called into action in events such as&#xD;
        pneumonia, influenza infection, and sepsis. This study will include a screening visit, a&#xD;
        statin therapy initiation visit (if the participant is in the statin therapy group), a&#xD;
        vaccination visit, and a series of follow-up visits. The statin medication will be dispensed&#xD;
        by the study staff with clear instructions on how to take the medication for two months (one&#xD;
        month prior to vaccination, and one month after vaccination). Other study procedures include&#xD;
        a collection of medical history and medications taken, a urine pregnancy test for&#xD;
        participants who are biologically able to become pregnant, a recording of vital signs, and a&#xD;
        collection of any adverse events that the participant experiences during their participation&#xD;
        in the study. The stool will be collected in one screening visit, at the vaccination visit,&#xD;
        and one follow-up visit. Safety tests to evaluate muscle health and liver function will be&#xD;
        obtained as well at screening and for participants selected to receive the statin therapy, at&#xD;
        two follow-up visits. Memory Aid will be completed by the participant after vaccination.&#xD;
  &#xD;
        The blood and stool samples collected during this study will be stored and tested to evaluate&#xD;
        how the immune system responds to statin therapy and vaccination over time. The remaining&#xD;
        unused samples will be stored for use in future research.&#xD;
  &#xD;
        This research will help advance the knowledge that researchers have on how the immune system&#xD;
        reacts to a vaccine if previously exposed to a statin therapy regimen. This will, in turn,&#xD;
        enable us to identify the factors that help predict the extent of durability of protection&#xD;
        gained from a specific vaccine. This may impact the way future vaccines are developed to&#xD;
        provide long-lasting immunity against infections.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 11, 2023</start_date>
    <completion_date type="Anticipated">March 31, 2026</completion_date>
    <primary_completion_date type="Anticipated">March 31, 2026</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>
      <primary_purpose>Basic Science</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Magnitude of the antibody (Ab) response to QIV in statin recipients and non-recipients.</measure>
      <time_frame>Up to 29 days after vaccine administration</time_frame>
      <description>Magnitude of neutralizing antibody responses against influenza vaccine strains at 29 days after vaccination among participants.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Frequency of adverse events (AEs)</measure>
      <time_frame>Until day 29 after vaccine administration</time_frame>
      <description>Adverse events of grade 2 or higher (AE, defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of the vaccine, without any judgment about causality) will be identified during questioning or examination of participants during study visits or receiving a safety contact from a participant.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Severity of adverse events (AEs)</measure>
      <time_frame>Until day 29 after vaccine administration</time_frame>
      <description>Adverse events (AE) will be graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 5.0</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Frequency of serious adverse events (SAEs)</measure>
      <time_frame>Up to 181 days after vaccine administration</time_frame>
      <description>Serious adverse events (SAE, defined as an AE that in the view of the investigator results in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect) will be identified during questioning or examination of participants during study visits or receiving a safety contact from a participant any time during the study.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Severity of serious adverse events</measure>
      <time_frame>Up to 181 days after vaccine administration</time_frame>
      <description>SAE will be graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 5.0.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">60</enrollment>
    <condition>Vaccine Response</condition>
    <arm_group>
      <arm_group_label>seasonal quadrivalent influenza vaccine (QIV)</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Participants will receive the seasonal QIV</description>
    </arm_group>
    <arm_group>
      <arm_group_label>statin therapy and a seasonal quadrivalent influenza vaccine (QIV)</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Participants randomized to the Statin + QIV arm will be asked to come back for an extra visit one month prior to the date of vaccination to start statin therapy.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Atorvastatin</intervention_name>
      <description>Atorvastatin is a lipid-lowering agent of the statin family that functions by blocking a rate-limiting enzyme, Hydroxymethylglutaryl-CoA (HMG-CoA) reductase, in lipid metabolism. This agent is commonly used for primary and secondary prevention of dyslipidemia. Participants will be asked to take Atorvastatin 80 mg daily at night, for 4 weeks prior to the vaccination, and continue the statin therapy for 4 weeks after vaccination.&#xD;
  The 80mg dose of atorvastatin allows for evaluation of the immunologic effects of statin medication with a short duration of therapy prior to vaccination.</description>
      <arm_group_label>statin therapy and a seasonal quadrivalent influenza vaccine (QIV)</arm_group_label>
      <other_name>Statin Therapy</other_name>
    </intervention>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>Quadrivalent seasonal influenza vaccine</intervention_name>
      <description>The FDA-approved quadrivalent seasonal influenza vaccine contains four distinct strains: two influenza A viruses and two influenza B viruses. The approved seasonal QIV will be purchased from the manufacturer to be given for each season of influenza.</description>
      <arm_group_label>seasonal quadrivalent influenza vaccine (QIV)</arm_group_label>
      <arm_group_label>statin therapy and a seasonal quadrivalent influenza vaccine (QIV)</arm_group_label>
      <other_name>Flu vaccine</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Able to understand and give informed consent.&#xD;
  &#xD;
            -  Age 18-50 years.&#xD;
  &#xD;
            -  Women of childbearing potential must agree to use effective birth control for the&#xD;
               first 3 months of the study. A negative urine pregnancy test must be documented prior&#xD;
               to vaccination.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  History of allergy or serious adverse reaction, including Guillain-Barré syndrome, to&#xD;
               a vaccine or vaccine products.&#xD;
  &#xD;
            -  History of a medical condition resulting in impaired immunity such as active solid&#xD;
               tumors, leukemia, lymphoma, use of immunosuppressive drugs, chemotherapy, or radiation&#xD;
               therapy. Persons with previous skin cancers or cured non-lymphatic tumors are not&#xD;
               excluded from the study.&#xD;
  &#xD;
            -  History of HIV, Hepatitis B, or Hepatitis C infection.&#xD;
  &#xD;
            -  Chronic clinically significant medical problems that could be considered active or&#xD;
               unstable (i.e. diagnosed within the past 3 months or requiring a change in medication&#xD;
               within the past 3 months). This includes (but is not limited to):&#xD;
  &#xD;
                 1. Insulin-dependent diabetes&#xD;
  &#xD;
                 2. Severe heart disease (including arrhythmias)&#xD;
  &#xD;
                 3. Severe lung disease&#xD;
  &#xD;
                 4. Severe liver disease&#xD;
  &#xD;
                 5. Severe kidney disease&#xD;
  &#xD;
                 6. Severe hypertension: defined as life-threatening consequences (e.g., malignant&#xD;
                    hypertension, transient or permanent neurologic deficit).&#xD;
  &#xD;
            -  BMI &gt; 30&#xD;
  &#xD;
            -  Current or previous use of statins or any other lipid-lowering drug.&#xD;
  &#xD;
            -  Pregnancy or breastfeeding or plans to become pregnant in the first 3 months of study&#xD;
               participation.&#xD;
  &#xD;
            -  History of influenza infection within the same influenza season.&#xD;
  &#xD;
            -  Receipt of blood products or immune globulin products within the prior 3 months.&#xD;
  &#xD;
            -  History of excessive alcohol consumption, drug use, psychiatric conditions, social&#xD;
               conditions, or occupational conditions that in the opinion of the investigator would&#xD;
               preclude compliance with the trial.&#xD;
  &#xD;
            -  Receipt of any live vaccines 30 days before or plans to receive any live vaccines 30&#xD;
               days after vaccination.&#xD;
  &#xD;
            -  Receipt of any inactivated vaccines 14 days before or plans to receive any inactivated&#xD;
               vaccines 14 days after vaccination.&#xD;
  &#xD;
          For participants randomized to the statin therapy + QIV group:&#xD;
  &#xD;
            -  The participant is currently taking any medication that has known interactions with&#xD;
               statin therapy.&#xD;
  &#xD;
            -  History of renal or hepatic impairment.&#xD;
  &#xD;
            -  Abnormal Safety lab results &gt;1.5 upper limit normal (ULN)&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>50 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Daniel S. Graciaa, MD, MPH, MSc</last_name>
      <role>Principal Investigator</role>
      <affiliation>Emory University</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Nadine Rouphael, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Emory University</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Varun Phadke, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Emory University</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Vin Tangpricha, MD, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Emory University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Daniel S. Graciaa, MD, MPH, MSc</last_name>
      <phone>404-712-9018 or 404-712-1370</phone>
      <email>dsgraci@emory.edu</email>
    </overall_contact>
    <location>
      <facility>
        <name>Hope Clinic</name>
        <address>
          <city>Atlanta</city>
          <state>Georgia</state>
          <zip>30322</zip>
          <country>United States</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 29, 2023</study_first_submitted>
    <study_first_submitted_qc>August 29, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 5, 2023</study_first_posted>
    <last_update_submitted>August 29, 2023</last_update_submitted>
    <last_update_submitted_qc>August 29, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 5, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Emory University</investigator_affiliation>
      <investigator_full_name>Daniel S. Graciaa, MD</investigator_full_name>
      <investigator_title>Assistant Professor</investigator_title>
    </responsible_party>
    <keyword>Flu Vaccine</keyword>
    <keyword>Statins</keyword>
    <keyword>Immunization Response</keyword>
    <keyword>seasonal quadrivalent influenza vaccine</keyword>
    <keyword>antibody (Ab) response</keyword>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Atorvastatin</mesh_term>
      <mesh_term>Vaccines</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>The research team will share de-identified participant data (including data dictionaries) and Transcriptomics data.</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_time_frame>The team will share the data immediately following the study publication.</ipd_time_frame>
      <ipd_access_criteria>Data will be available via NCBI GEO</ipd_access_criteria>
      <ipd_url>http://www.ncbi.nlm.nih.gov/geo/</ipd_url>
    </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/NCT06024096
  org study id: STUDY00006239
  nct id: NCT06024096
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  is us export: Yes
  This study is being done to answer the question: Does the use of statin lipid-lowering
        medication change the effect of influenza vaccine? The research team will use the knowledge
        gained from answering this question to understand how this medication affects long-lasting
        immune responses to vaccines. The researchers will study the immune response to the influenza
        vaccine in the blood (where antibodies are). The team will also look at how statin therapy
        affects the bacteria that live in the gut by collecting stool samples. To be in this
        research, participants must be adults willing to receive vaccines.
  Statins are widely used for their lipid-lowering and cardiovascular protective effects.
        Additional research has shown that statins can be anti-inflammatory and play a part in
        modulating the immune system. These effects are called into action in events such as
        pneumonia, influenza infection, and sepsis. This study will include a screening visit, a
        statin therapy initiation visit (if the participant is in the statin therapy group), a
        vaccination visit, and a series of follow-up visits. The statin medication will be dispensed
        by the study staff with clear instructions on how to take the medication for two months (one
        month prior to vaccination, and one month after vaccination). Other study procedures include
        a collection of medical history and medications taken, a urine pregnancy test for
        participants who are biologically able to become pregnant, a recording of vital signs, and a
        collection of any adverse events that the participant experiences during their participation
        in the study. The stool will be collected in one screening visit, at the vaccination visit,
        and one follow-up visit. Safety tests to evaluate muscle health and liver function will be
        obtained as well at screening and for participants selected to receive the statin therapy, at
        two follow-up visits. Memory Aid will be completed by the participant after vaccination.
  
        The blood and stool samples collected during this study will be stored and tested to evaluate
        how the immune system responds to statin therapy and vaccination over time. The remaining
        unused samples will be stored for use in future research.
  
        This research will help advance the knowledge that researchers have on how the immune system
        reacts to a vaccine if previously exposed to a statin therapy regimen. This will, in turn,
        enable us to identify the factors that help predict the extent of durability of protection
        gained from a specific vaccine. This may impact the way future vaccines are developed to
        provide long-lasting immunity against infections.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Basic Science
  masking: None (Open Label)
  measure: Magnitude of the antibody (Ab) response to QIV in statin recipients and non-recipients.
  time frame: Up to 29 days after vaccine administration
  description: Magnitude of neutralizing antibody responses against influenza vaccine strains at 29 days after vaccination among participants.
  measure: Frequency of adverse events (AEs)
  time frame: Until day 29 after vaccine administration
  description: Adverse events of grade 2 or higher (AE, defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of the vaccine, without any judgment about causality) will be identified during questioning or examination of participants during study visits or receiving a safety contact from a participant.
  measure: Severity of adverse events (AEs)
  time frame: Until day 29 after vaccine administration
  description: Adverse events (AE) will be graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 5.0
  measure: Frequency of serious adverse events (SAEs)
  time frame: Up to 181 days after vaccine administration
  description: Serious adverse events (SAE, defined as an AE that in the view of the investigator results in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect) will be identified during questioning or examination of participants during study visits or receiving a safety contact from a participant any time during the study.
  measure: Severity of serious adverse events
  time frame: Up to 181 days after vaccine administration
  description: SAE will be graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 5.0.
  arm group label: seasonal quadrivalent influenza vaccine (QIV)
  arm group type: Active Comparator
  description: Participants will receive the seasonal QIV
  arm group label: statin therapy and a seasonal quadrivalent influenza vaccine (QIV)
  arm group type: Active Comparator
  description: Participants randomized to the Statin + QIV arm will be asked to come back for an extra visit one month prior to the date of vaccination to start statin therapy.
  intervention type: Drug
  intervention name: Atorvastatin
  description: Atorvastatin is a lipid-lowering agent of the statin family that functions by blocking a rate-limiting enzyme, Hydroxymethylglutaryl-CoA (HMG-CoA) reductase, in lipid metabolism. This agent is commonly used for primary and secondary prevention of dyslipidemia. Participants will be asked to take Atorvastatin 80 mg daily at night, for 4 weeks prior to the vaccination, and continue the statin therapy for 4 weeks after vaccination.
  The 80mg dose of atorvastatin allows for evaluation of the immunologic effects of statin medication with a short duration of therapy prior to vaccination.
  arm group label: statin therapy and a seasonal quadrivalent influenza vaccine (QIV)
  other name: Statin Therapy
  intervention type: Biological
  intervention name: Quadrivalent seasonal influenza vaccine
  description: The FDA-approved quadrivalent seasonal influenza vaccine contains four distinct strains: two influenza A viruses and two influenza B viruses. The approved seasonal QIV will be purchased from the manufacturer to be given for each season of influenza.
  arm group label: seasonal quadrivalent influenza vaccine (QIV)
  arm group label: statin therapy and a seasonal quadrivalent influenza vaccine (QIV)
  other name: Flu vaccine
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 50 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Daniel S. Graciaa, MD, MPH, MSc
  role: Principal Investigator
  affiliation: Emory University
  last name: Nadine Rouphael, MD
  role: Principal Investigator
  affiliation: Emory University
  last name: Varun Phadke, MD
  role: Principal Investigator
  affiliation: Emory University
  last name: Vin Tangpricha, MD, PhD
  role: Principal Investigator
  affiliation: Emory University
  last name: Daniel S. Graciaa, MD, MPH, MSc
  phone: 404-712-9018 or 404-712-1370
  email: dsgraci@emory.edu
  facility: 
  country: United States
  responsible party type: Principal Investigator
  investigator affiliation: Emory University
  investigator full name: Daniel S. Graciaa, MD
  investigator title: Assistant Professor
  mesh term: Atorvastatin
  mesh term: Vaccines
  sharing ipd: Yes
  ipd description: The research team will share de-identified participant data (including data dictionaries) and Transcriptomics data.
  ipd info type: Study Protocol
  ipd time frame: The team will share the data immediately following the study publication.
  ipd access criteria: Data will be available via NCBI GEO
  ipd url: http://www.ncbi.nlm.nih.gov/geo/