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/NCT06005298</url>
    </required_header>
    <id_info>
      <org_study_id>22.0606</org_study_id>
      <secondary_id>1R01AA030485-01</secondary_id>
      <nct_id>NCT06005298</nct_id>
    </id_info>
    <brief_title>Alcohol Misuse, Gut Microbial Dysbiosis and PrEP Care Continuum: Application and Efficacy of SBIRT Intervention</brief_title>
    <acronym>SEAL</acronym>
    <official_title>Alcohol Misuse, Gut Microbial Dysbiosis and PrEP Care Continuum: Application and Efficacy of SBIRT Intervention (SEAL)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Shirish S Barve</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>National Institute on Alcohol Abuse and Alcoholism (NIAAA)</agency>
        <agency_class>NIH</agency_class>
      </collaborator>
    </sponsors>
    <source>University of Louisville</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This randomized control trial study among Pre-exposure prophylactic users (PrEP) aims to&#xD;
        learn and determine the efficacy of Screening, brief intervention, and referral to treatment&#xD;
        (SBRIT) in reducing the risk of alcohol use. The main questions it aims to answer are:&#xD;
  &#xD;
          1. How alcohol use impacts the PrEP continuum and to understand how early intervention and&#xD;
             treatment approach affects alcohol use and PrEP adherence.&#xD;
  &#xD;
          2. Investigate the effectiveness of the SBIRT intervention in preventing hazardous alcohol&#xD;
             use and its impact on gut dysbiosis in PrEP users.&#xD;
  &#xD;
          3. To determine alterations in the gut microbiome (dysbiosis), intestinal homeostasis,&#xD;
             systemic inflammation, and markers of liver disease associated with hazardous alcohol&#xD;
             use among PrEP users.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The study pursues a randomized control trial (RCT) with persons who use pre-exposure&#xD;
        prophylaxis (PrEP) to determine the efficacy of SBIRT (Screening, Brief Intervention, &amp;&#xD;
        Referral to Treatment) in reducing the risk of alcohol drinking and associated pathogenic&#xD;
        changes in the gut liver axis.&#xD;
  &#xD;
        Participants in this study will attend visits at 3 months, 6 months,s and 12 months for about&#xD;
        60 to 90 minutes. These visits may include filling out a survey, participating in an&#xD;
        interview, meeting with an SBIRT interventionist, and providing the aforementioned samples:&#xD;
        Blood, urine, stool, saliva, oral and vaginal, if applicable.&#xD;
  &#xD;
        This study will use a syndemic approach to expand the HIV/AIDS prevention toolkit among&#xD;
        populations impacted by alcohol with a range of patterns of episodic and long-term use and&#xD;
        associated behavioral and biological risks for HIV acquisition.&#xD;
  &#xD;
        Specifically, the team will execute a randomized control trial among Pre-Exposure Prophylaxis&#xD;
        (PrEP) users demonstrating heightened alcohol use to test the effectiveness of the Screening,&#xD;
        Brief Intervention, &amp; Referral to Treatment (SBIRT) intervention to reduce alcohol use and&#xD;
        examine the subsequent impact on the gut microbiome compared to individuals receiving&#xD;
        treatment as usual and PrEP users not demonstrating elevated alcohol use. Finally, we will&#xD;
        employ qualitative methods (in-depth interviews) and analysis to understand decision-making&#xD;
        factors influencing PrEP adherence and alcohol use over time.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">September 1, 2027</completion_date>
    <primary_completion_date type="Anticipated">September 1, 2024</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>Prevention</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Number of Patients with Hazardous Alcohol use</measure>
      <time_frame>baseline, 3 months, 6 months, 12 months</time_frame>
      <description>Hazardous alcohol use will decrease in the experimental group (SBIRT) compared to the control group (treatment as usual). This will be measured by the Alcohol Use Disorders Identification Test (AUDIT), which is an alcohol screening instrument, the TLFB / Timeline Followback, which involves asking participants to retrospectively estimate their alcohol use 7 days to 2 years prior to the interview date, and the TAPS Tool / The Tobacco, Alcohol, Prescription medications, and other Substance Tool, which is a screening and assessment tool for alcohol use in the past year.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of Patients with Gut Microbial alpha diversity measured by the Shannon index</measure>
      <time_frame>baseline, 3 months, 6 months, 12 months</time_frame>
      <description>Another significant primary outcomes for this aim is gut microbial alpha diversity measured by the Shannon index.&#xD;
  Among all PrEP users, the comparison will be done between those who drink alcohol with those who do not drink alcohol in terms of the Shannon index. This will be analyzed using stool samples.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of Patients with Gut Microbial alpha diversity measured by abundance of bacteria</measure>
      <time_frame>baseline, 3 months, 6 months, 12 months</time_frame>
      <description>The primary outcome for this aim- Gut microbial alpha diversity measurement using the abundance of bacteria family Lachnospiraceae.&#xD;
  This involves transforming the relative abundance (RA) of Lachnospiraceae during logit transformation to expand the RA. This will be analyzed using stool samples.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of Patients reaching PrEP adherence</measure>
      <time_frame>baseline, 3 months, 6 months, 12 months</time_frame>
      <description>PrEP adherence will increase in the experimental group (SBIRT) compared to the control group (treatment as usual). This will be measured using a single-item measure using self-report (Blumenthal et al, 2019), a medication diary via an app (Round Health), and/or by recording medication on a calendar provided by the research team (90 days), and/or pill counts (Hannaford, Arens &amp; Koenig, 2021).</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of Patients Engaged in the PrEP care continuum</measure>
      <time_frame>baseline, 3 months, 6 months, 12 months</time_frame>
      <description>Hazardous alcohol use decreases movement through the PrEP care continuum. This will be measured by a) AUDIT, and b) categorical data on phase in which patient disengaged from the PrEP care continuum (uptake, adherence, retention).</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Number of Patients reporting self-efficacy related to PrEP or confidence in one's ability to carry out behaviors important to PrEP adherence</measure>
      <time_frame>baseline, 3 months, 6 months, 12 months</time_frame>
      <description>Self-efficacy related to PrEP or confidence in one's ability to carry out behaviors important to PrEP adherence will increase in the experimental group (SBIRT) compared to the control group (treatment as usual). This will be measured by the PrEP self-efficacy scale.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of Patients reporting PrEP stigma</measure>
      <time_frame>baseline, 3 months, 6 months, 12 months</time_frame>
      <description>PrEP stigma will decrease in the experimental group (SBIRT) compared to the control group (treatment as usual). This will be measured by the PrEP Stigma Likert Scale.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of Patients reporting self-efficacy related to abstaining from alcohol</measure>
      <time_frame>baseline, 3 months, 6 months, 12 months</time_frame>
      <description>Self-efficacy related to abstaining from alcohol will increase in the experimental group (SBIRT) compared to the control group (treatment as usual). This will be measured by the AASE / Alcohol Abstinence Self-Efficacy Scale.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of Patients reporting use of other illicit drugs</measure>
      <time_frame>baseline, 3 months, 6 months, 12 months</time_frame>
      <description>Use of other illicit drugs will decrease in the experimental group (SBIRT) compared to the control group (treatment as usual). This will be measured by the ASSIST (version 2.0) / Alcohol, Smoking and Substance Involvement Screening Test which is a screening instrument for Cannabis, Cocaine, Prescription Stimulants, Methamphetamine, Inhalants, Sedatives, Hallucinogens, Street Opioids, Prescription Opioids, other drugs, the TLFB / Timeline Followback, which involves asking participants to retrospectively estimate their illicit drug use 7 days to 2 years prior to the interview date, and the TAPS Tool / The Tobacco, Alcohol, Prescription medications, and other Substance Tool, which is a screening and assessment tool for tobacco use, alcohol use, prescription medication misuse, and illicit substance use in the past year.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of Patients reporting Sense of hope as evidenced by improved sense of goal directed energy and/or planning to accomplish goals m</measure>
      <time_frame>baseline, 3 months, 6 months, 12 months</time_frame>
      <description>Sense of hope will increase in the experimental group (SBIRT) compared to the control group (treatment as usual). This will be measured by the Adult Hope Scale (AHS).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of Patients reporting Symptoms of depression</measure>
      <time_frame>baseline, 3 months, 6 months, 12 months</time_frame>
      <description>Symptoms of depression will decrease in the experimental group (SBIRT) compared to the control group (treatment as usual). This will be measured by the CES-D / Center for Epidemiologic Studies Depression Scale.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of Patients reporting Symptoms of anxiety</measure>
      <time_frame>baseline, 3 months, 6 months, 12 months</time_frame>
      <description>Symptoms of anxiety will decrease in the experimental group (SBIRT) compared to the control group (treatment as usual). This will be measured by the CESA / Center for Epidemiologic Studies Anxiety Scale.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of Patients with Gut microbiome/bacterial composition at the genera level, and functional characteristics of genes for bacterial populations</measure>
      <time_frame>baseline, 3 months, 6 months, 12 months</time_frame>
      <description>Secondary outcomes from gut microbiome evaluation will be bacterial composition at the genera level, and functional characteristics of genes for bacterial populations. This will be analyzed using stool samples.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of Patients with Immune Activation, Inflammation and liver injury related outcomes</measure>
      <time_frame>baseline, 3 months, 6 months, 12 months</time_frame>
      <description>Secondary outcomes from plasma/blood samples will be i) Intestinal fatty acid binding protein (IFABP) and lipopolysaccharide (LPS) for gut permeability and microbial translocation; ii) sCD14 and inflammatory cytokines including TNFα, IL-1β, MCP-1, IL-8, IL-6 for immune activation and inflammation and iii)AST, ALT and CK18 for liver injury.</description>
    </secondary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">120</enrollment>
    <condition>Alcohol Use Disorder</condition>
    <condition>Risk Behavior, Health</condition>
    <condition>Dysbiosis</condition>
    <condition>HIV Infections</condition>
    <arm_group>
      <arm_group_label>AUDIT &lt;8</arm_group_label>
      <arm_group_type>No Intervention</arm_group_type>
      <description>Participants whose audit score is less than eight are assigned to this arm. AUDIT is a 10-item screening tool developed by the World Health Organization (WHO) to assess alcohol consumption, dependence, and experience of alcohol-related harm. AUDIT &lt;8 is non-hazardous.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>AUDIT &gt;8 + SBIRT</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>This is an experimental arm, and AUDIT &gt;8 is hazardous. The goal is to make connections on the impact of the SBIRT intervention on PrEP engagement and alcohol use among the participants to create a full picture of the impact of the intervention on groups exhibiting different types of alcohol use.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>AUDIT &gt; 8 NO SBIRT</arm_group_label>
      <arm_group_type>No Intervention</arm_group_type>
      <description>This is NOT an experimental arm, despite an AUDIT score &gt; 8.</description>
    </arm_group>
    <intervention>
      <intervention_type>Behavioral</intervention_type>
      <intervention_name>Screening, Brief Intervention, Referral to Treatment (SBIRT)</intervention_name>
      <description>SBIRT has been defined by SAMHSA as a comprehensive, integrated, public health approach to the delivery of early intervention for individuals with risky alcohol and drug use and the timely referral to more intensive substance abuse treatment for those who have substance abuse disorders. There is consensus that a comprehensive SBIRT model includes screening, brief intervention/brief treatment, and referral to treatment. In addition there are following characteristics:&#xD;
  It is brief (e.g., typically about 5-10 minutes for brief interventions; about 5 to 12 sessions for brief treatments)&#xD;
  The screening is universal.&#xD;
  One or more specific behaviors related to risky alcohol and drug use are targeted.&#xD;
  The services occur in a public health non-substance abuse treatment setting.&#xD;
  It is comprehensive (comprised of screening, brief intervention/treatment, and referral to treatment).&#xD;
  Strong research or experiential evidence supports the model's effectiveness.</description>
      <arm_group_label>AUDIT &gt;8 + SBIRT</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Age: 18-85 years&#xD;
  &#xD;
            -  Confirmation of seronegative HIV, Hep B, and Hep C status&#xD;
  &#xD;
            -  PrEP users&#xD;
  &#xD;
            -  English-speaking or Spanish speaking&#xD;
  &#xD;
            -  Cognitively competent to provide consent&#xD;
  &#xD;
            -  Attend a participating healthcare facility&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Inability to consent&#xD;
  &#xD;
            -  Existing diagnosis of major psychiatric illness&#xD;
  &#xD;
            -  Unstable medical conditions (e.g., cancer)&#xD;
  &#xD;
            -  Taking immunosuppressants or Chemotherapy&#xD;
  &#xD;
            -  Taking daily antibiotics or probiotics&#xD;
  &#xD;
            -  Severe gastrointestinal/liver disease&#xD;
  &#xD;
            -  Autoimmune disease&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>85 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Shirish Barve, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>University of Louisville</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Andrea Reyes Vega, MD, MSc</last_name>
      <phone>502852884</phone>
      <email>a0reye02@louisville.edu</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Vania Remenik, MD</last_name>
      <phone>5028528884</phone>
      <email>vania.remenik@louisville.edu</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>University of Louisville</name>
        <address>
          <city>Louisville</city>
          <state>Kentucky</state>
          <zip>40202</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Andrea M Reyes Vega, MD,MSc</last_name>
        <phone>502-852-8884</phone>
        <email>a0reye02@louisville.edu</email>
      </contact>
      <contact_backup>
        <last_name>Vania Remenik, MD</last_name>
        <email>vania.remenik@louisville.edu</email>
      </contact_backup>
      <investigator>
        <last_name>Shirish Barve, PhD</last_name>
        <role>Principal Investigator</role>
      </investigator>
      <investigator>
        <last_name>Smita Ghare, PhD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Jelani Kerr, PhD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Lesley Harris, PhD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Andrea Reyes Vega, MD, MSc</last_name>
        <role>Sub-Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <results_reference>
      <citation>Higgins-Biddle JC, Babor TF. A review of the Alcohol Use Disorders Identification Test (AUDIT), AUDIT-C, and USAUDIT for screening in the United States: Past issues and future directions. Am J Drug Alcohol Abuse. 2018;44(6):578-586. doi: 10.1080/00952990.2018.1456545. Epub 2018 May 3.</citation>
      <PMID>29723083</PMID>
    </results_reference>
    <results_reference>
      <citation>Conigrave KM, Hall WD, Saunders JB. The AUDIT questionnaire: choosing a cut-off score. Alcohol Use Disorder Identification Test. Addiction. 1995 Oct;90(10):1349-56. doi: 10.1046/j.1360-0443.1995.901013496.x.</citation>
      <PMID>8616463</PMID>
    </results_reference>
    <results_reference>
      <citation>Saunders JB, Aasland OG, Babor TF, de la Fuente JR, Grant M. Development of the Alcohol Use Disorders Identification Test (AUDIT): WHO Collaborative Project on Early Detection of Persons with Harmful Alcohol Consumption--II. Addiction. 1993 Jun;88(6):791-804. doi: 10.1111/j.1360-0443.1993.tb02093.x.</citation>
      <PMID>8329970</PMID>
    </results_reference>
    <results_reference>
      <citation>Humeniuk R, Henry-Edwards S, Ali R, Poznyak V, Monteiro MGea. The Alcohol, Smoking and Substance involvement Screening Test (ASSIST): manual for use in primary care. Geneva, Swizterland World Health Organization;2010.</citation>
    </results_reference>
    <results_reference>
      <citation>Zhang W, O'Brien N, Forrest JI, Salters KA, Patterson TL, Montaner JS, Hogg RS, Lima VD. Validating a shortened depression scale (10 item CES-D) among HIV-positive people in British Columbia, Canada. PLoS One. 2012;7(7):e40793. doi: 10.1371/journal.pone.0040793. Epub 2012 Jul 19.</citation>
      <PMID>22829885</PMID>
    </results_reference>
    <results_reference>
      <citation>Ghare S, Singhal R, Bryant V, Gautam S, Tirumala CC, Srisailam PK, Reyes-Vega A, Ghooray D, McClain CJ, Hoffman K, Petrosino J, Bryant K, Govind V, Cohen R, Cook RL, Barve S. Age-Associated Gut Dysbiosis, Marked by Loss of Butyrogenic Potential, Correlates With Altered Plasma Tryptophan Metabolites in Older People Living With HIV. J Acquir Immune Defic Syndr. 2022 Feb 1;89(Suppl 1):S56-S64. doi: 10.1097/QAI.0000000000002866.</citation>
      <PMID>35015746</PMID>
    </results_reference>
    <results_reference>
      <citation>Fulcher JA, Li F, Cook RR, Zabih S, Louie A, Okochi H, Tobin NH, Gandhi M, Shoptaw S, Gorbach PM, Aldrovandi GM. Rectal Microbiome Alterations Associated With Oral Human Immunodeficiency Virus Pre-Exposure Prophylaxis. Open Forum Infect Dis. 2019 Oct 29;6(11):ofz463. doi: 10.1093/ofid/ofz463. eCollection 2019 Nov.</citation>
      <PMID>32258202</PMID>
    </results_reference>
    <results_reference>
      <citation>Dube MP, Park SY, Ross H, Love TMT, Morris SR, Lee HY. Daily HIV pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate-emtricitabine reduced Streptococcus and increased Erysipelotrichaceae in rectal microbiota. Sci Rep. 2018 Oct 12;8(1):15212. doi: 10.1038/s41598-018-33524-6.</citation>
      <PMID>30315206</PMID>
    </results_reference>
    <results_reference>
      <citation>Perler BK, Reinhart EM, Montgomery M, Maynard M, Shapiro JM, Belenky P, Chan PA. Evaluation of the Microbiome in Men Taking Pre-exposure Prophylaxis for HIV Prevention. AIDS Behav. 2021 Jul;25(7):2005-2013. doi: 10.1007/s10461-020-03130-7. Epub 2021 Jan 4.</citation>
      <PMID>33394167</PMID>
    </results_reference>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>October 28, 2022</study_first_submitted>
    <study_first_submitted_qc>August 16, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 22, 2023</study_first_posted>
    <last_update_submitted>August 22, 2023</last_update_submitted>
    <last_update_submitted_qc>August 22, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 24, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor-Investigator</responsible_party_type>
      <investigator_affiliation>University of Louisville</investigator_affiliation>
      <investigator_full_name>Shirish S Barve</investigator_full_name>
      <investigator_title>Professor</investigator_title>
    </responsible_party>
    <keyword>PrEP</keyword>
    <keyword>Alcohol</keyword>
    <keyword>SBIRT</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Dysbiosis</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/NCT06005298
  org study id: 22.0606
  secondary id: 1R01AA030485-01
  nct id: NCT06005298
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  This randomized control trial study among Pre-exposure prophylactic users (PrEP) aims to
        learn and determine the efficacy of Screening, brief intervention, and referral to treatment
        (SBRIT) in reducing the risk of alcohol use. The main questions it aims to answer are:
  
          1. How alcohol use impacts the PrEP continuum and to understand how early intervention and
             treatment approach affects alcohol use and PrEP adherence.
  
          2. Investigate the effectiveness of the SBIRT intervention in preventing hazardous alcohol
             use and its impact on gut dysbiosis in PrEP users.
  
          3. To determine alterations in the gut microbiome (dysbiosis), intestinal homeostasis,
             systemic inflammation, and markers of liver disease associated with hazardous alcohol
             use among PrEP users.
  The study pursues a randomized control trial (RCT) with persons who use pre-exposure
        prophylaxis (PrEP) to determine the efficacy of SBIRT (Screening, Brief Intervention, &
        Referral to Treatment) in reducing the risk of alcohol drinking and associated pathogenic
        changes in the gut liver axis.
  
        Participants in this study will attend visits at 3 months, 6 months,s and 12 months for about
        60 to 90 minutes. These visits may include filling out a survey, participating in an
        interview, meeting with an SBIRT interventionist, and providing the aforementioned samples:
        Blood, urine, stool, saliva, oral and vaginal, if applicable.
  
        This study will use a syndemic approach to expand the HIV/AIDS prevention toolkit among
        populations impacted by alcohol with a range of patterns of episodic and long-term use and
        associated behavioral and biological risks for HIV acquisition.
  
        Specifically, the team will execute a randomized control trial among Pre-Exposure Prophylaxis
        (PrEP) users demonstrating heightened alcohol use to test the effectiveness of the Screening,
        Brief Intervention, & Referral to Treatment (SBIRT) intervention to reduce alcohol use and
        examine the subsequent impact on the gut microbiome compared to individuals receiving
        treatment as usual and PrEP users not demonstrating elevated alcohol use. Finally, we will
        employ qualitative methods (in-depth interviews) and analysis to understand decision-making
        factors influencing PrEP adherence and alcohol use over time.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Prevention
  masking: None (Open Label)
  measure: Number of Patients with Hazardous Alcohol use
  time frame: baseline, 3 months, 6 months, 12 months
  description: Hazardous alcohol use will decrease in the experimental group (SBIRT) compared to the control group (treatment as usual). This will be measured by the Alcohol Use Disorders Identification Test (AUDIT), which is an alcohol screening instrument, the TLFB / Timeline Followback, which involves asking participants to retrospectively estimate their alcohol use 7 days to 2 years prior to the interview date, and the TAPS Tool / The Tobacco, Alcohol, Prescription medications, and other Substance Tool, which is a screening and assessment tool for alcohol use in the past year.
  measure: Number of Patients with Gut Microbial alpha diversity measured by the Shannon index
  time frame: baseline, 3 months, 6 months, 12 months
  description: Another significant primary outcomes for this aim is gut microbial alpha diversity measured by the Shannon index.
  Among all PrEP users, the comparison will be done between those who drink alcohol with those who do not drink alcohol in terms of the Shannon index. This will be analyzed using stool samples.
  measure: Number of Patients with Gut Microbial alpha diversity measured by abundance of bacteria
  time frame: baseline, 3 months, 6 months, 12 months
  description: The primary outcome for this aim- Gut microbial alpha diversity measurement using the abundance of bacteria family Lachnospiraceae.
  This involves transforming the relative abundance (RA) of Lachnospiraceae during logit transformation to expand the RA. This will be analyzed using stool samples.
  measure: Number of Patients reaching PrEP adherence
  time frame: baseline, 3 months, 6 months, 12 months
  description: PrEP adherence will increase in the experimental group (SBIRT) compared to the control group (treatment as usual). This will be measured using a single-item measure using self-report (Blumenthal et al, 2019), a medication diary via an app (Round Health), and/or by recording medication on a calendar provided by the research team (90 days), and/or pill counts (Hannaford, Arens & Koenig, 2021).
  measure: Number of Patients Engaged in the PrEP care continuum
  time frame: baseline, 3 months, 6 months, 12 months
  description: Hazardous alcohol use decreases movement through the PrEP care continuum. This will be measured by a) AUDIT, and b) categorical data on phase in which patient disengaged from the PrEP care continuum (uptake, adherence, retention).
  measure: Number of Patients reporting self-efficacy related to PrEP or confidence in one's ability to carry out behaviors important to PrEP adherence
  time frame: baseline, 3 months, 6 months, 12 months
  description: Self-efficacy related to PrEP or confidence in one's ability to carry out behaviors important to PrEP adherence will increase in the experimental group (SBIRT) compared to the control group (treatment as usual). This will be measured by the PrEP self-efficacy scale.
  measure: Number of Patients reporting PrEP stigma
  time frame: baseline, 3 months, 6 months, 12 months
  description: PrEP stigma will decrease in the experimental group (SBIRT) compared to the control group (treatment as usual). This will be measured by the PrEP Stigma Likert Scale.
  measure: Number of Patients reporting self-efficacy related to abstaining from alcohol
  time frame: baseline, 3 months, 6 months, 12 months
  description: Self-efficacy related to abstaining from alcohol will increase in the experimental group (SBIRT) compared to the control group (treatment as usual). This will be measured by the AASE / Alcohol Abstinence Self-Efficacy Scale.
  measure: Number of Patients reporting use of other illicit drugs
  time frame: baseline, 3 months, 6 months, 12 months
  description: Use of other illicit drugs will decrease in the experimental group (SBIRT) compared to the control group (treatment as usual). This will be measured by the ASSIST (version 2.0) / Alcohol, Smoking and Substance Involvement Screening Test which is a screening instrument for Cannabis, Cocaine, Prescription Stimulants, Methamphetamine, Inhalants, Sedatives, Hallucinogens, Street Opioids, Prescription Opioids, other drugs, the TLFB / Timeline Followback, which involves asking participants to retrospectively estimate their illicit drug use 7 days to 2 years prior to the interview date, and the TAPS Tool / The Tobacco, Alcohol, Prescription medications, and other Substance Tool, which is a screening and assessment tool for tobacco use, alcohol use, prescription medication misuse, and illicit substance use in the past year.
  measure: Number of Patients reporting Sense of hope as evidenced by improved sense of goal directed energy and/or planning to accomplish goals m
  time frame: baseline, 3 months, 6 months, 12 months
  description: Sense of hope will increase in the experimental group (SBIRT) compared to the control group (treatment as usual). This will be measured by the Adult Hope Scale (AHS).
  measure: Number of Patients reporting Symptoms of depression
  time frame: baseline, 3 months, 6 months, 12 months
  description: Symptoms of depression will decrease in the experimental group (SBIRT) compared to the control group (treatment as usual). This will be measured by the CES-D / Center for Epidemiologic Studies Depression Scale.
  measure: Number of Patients reporting Symptoms of anxiety
  time frame: baseline, 3 months, 6 months, 12 months
  description: Symptoms of anxiety will decrease in the experimental group (SBIRT) compared to the control group (treatment as usual). This will be measured by the CESA / Center for Epidemiologic Studies Anxiety Scale.
  measure: Number of Patients with Gut microbiome/bacterial composition at the genera level, and functional characteristics of genes for bacterial populations
  time frame: baseline, 3 months, 6 months, 12 months
  description: Secondary outcomes from gut microbiome evaluation will be bacterial composition at the genera level, and functional characteristics of genes for bacterial populations. This will be analyzed using stool samples.
  measure: Number of Patients with Immune Activation, Inflammation and liver injury related outcomes
  time frame: baseline, 3 months, 6 months, 12 months
  description: Secondary outcomes from plasma/blood samples will be i) Intestinal fatty acid binding protein (IFABP) and lipopolysaccharide (LPS) for gut permeability and microbial translocation; ii) sCD14 and inflammatory cytokines including TNFα, IL-1β, MCP-1, IL-8, IL-6 for immune activation and inflammation and iii)AST, ALT and CK18 for liver injury.
  arm group label: AUDIT <8
  arm group type: No Intervention
  description: Participants whose audit score is less than eight are assigned to this arm. AUDIT is a 10-item screening tool developed by the World Health Organization (WHO) to assess alcohol consumption, dependence, and experience of alcohol-related harm. AUDIT <8 is non-hazardous.
  arm group label: AUDIT >8 + SBIRT
  arm group type: Experimental
  description: This is an experimental arm, and AUDIT >8 is hazardous. The goal is to make connections on the impact of the SBIRT intervention on PrEP engagement and alcohol use among the participants to create a full picture of the impact of the intervention on groups exhibiting different types of alcohol use.
  arm group label: AUDIT > 8 NO SBIRT
  arm group type: No Intervention
  description: This is NOT an experimental arm, despite an AUDIT score > 8.
  intervention type: Behavioral
  intervention name: Screening, Brief Intervention, Referral to Treatment (SBIRT)
  description: SBIRT has been defined by SAMHSA as a comprehensive, integrated, public health approach to the delivery of early intervention for individuals with risky alcohol and drug use and the timely referral to more intensive substance abuse treatment for those who have substance abuse disorders. There is consensus that a comprehensive SBIRT model includes screening, brief intervention/brief treatment, and referral to treatment. In addition there are following characteristics:
  It is brief (e.g., typically about 5-10 minutes for brief interventions; about 5 to 12 sessions for brief treatments)
  The screening is universal.
  One or more specific behaviors related to risky alcohol and drug use are targeted.
  The services occur in a public health non-substance abuse treatment setting.
  It is comprehensive (comprised of screening, brief intervention/treatment, and referral to treatment).
  Strong research or experiential evidence supports the model's effectiveness.
  arm group label: AUDIT >8 + SBIRT
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 85 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Shirish Barve, PhD
  role: Principal Investigator
  affiliation: University of Louisville
  last name: Andrea Reyes Vega, MD, MSc
  phone: 502852884
  email: a0reye02@louisville.edu
  last name: Vania Remenik, MD
  phone: 5028528884
  email: vania.remenik@louisville.edu
  facility: 
  contact: 
  contact backup: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  country: United States
  citation: Higgins-Biddle JC, Babor TF. A review of the Alcohol Use Disorders Identification Test (AUDIT), AUDIT-C, and USAUDIT for screening in the United States: Past issues and future directions. Am J Drug Alcohol Abuse. 2018;44(6):578-586. doi: 10.1080/00952990.2018.1456545. Epub 2018 May 3.
  PMID: 29723083
  citation: Conigrave KM, Hall WD, Saunders JB. The AUDIT questionnaire: choosing a cut-off score. Alcohol Use Disorder Identification Test. Addiction. 1995 Oct;90(10):1349-56. doi: 10.1046/j.1360-0443.1995.901013496.x.
  PMID: 8616463
  citation: Saunders JB, Aasland OG, Babor TF, de la Fuente JR, Grant M. Development of the Alcohol Use Disorders Identification Test (AUDIT): WHO Collaborative Project on Early Detection of Persons with Harmful Alcohol Consumption--II. Addiction. 1993 Jun;88(6):791-804. doi: 10.1111/j.1360-0443.1993.tb02093.x.
  PMID: 8329970
  citation: Humeniuk R, Henry-Edwards S, Ali R, Poznyak V, Monteiro MGea. The Alcohol, Smoking and Substance involvement Screening Test (ASSIST): manual for use in primary care. Geneva, Swizterland World Health Organization;2010.
  citation: Zhang W, O'Brien N, Forrest JI, Salters KA, Patterson TL, Montaner JS, Hogg RS, Lima VD. Validating a shortened depression scale (10 item CES-D) among HIV-positive people in British Columbia, Canada. PLoS One. 2012;7(7):e40793. doi: 10.1371/journal.pone.0040793. Epub 2012 Jul 19.
  PMID: 22829885
  citation: Ghare S, Singhal R, Bryant V, Gautam S, Tirumala CC, Srisailam PK, Reyes-Vega A, Ghooray D, McClain CJ, Hoffman K, Petrosino J, Bryant K, Govind V, Cohen R, Cook RL, Barve S. Age-Associated Gut Dysbiosis, Marked by Loss of Butyrogenic Potential, Correlates With Altered Plasma Tryptophan Metabolites in Older People Living With HIV. J Acquir Immune Defic Syndr. 2022 Feb 1;89(Suppl 1):S56-S64. doi: 10.1097/QAI.0000000000002866.
  PMID: 35015746
  citation: Fulcher JA, Li F, Cook RR, Zabih S, Louie A, Okochi H, Tobin NH, Gandhi M, Shoptaw S, Gorbach PM, Aldrovandi GM. Rectal Microbiome Alterations Associated With Oral Human Immunodeficiency Virus Pre-Exposure Prophylaxis. Open Forum Infect Dis. 2019 Oct 29;6(11):ofz463. doi: 10.1093/ofid/ofz463. eCollection 2019 Nov.
  PMID: 32258202
  citation: Dube MP, Park SY, Ross H, Love TMT, Morris SR, Lee HY. Daily HIV pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate-emtricitabine reduced Streptococcus and increased Erysipelotrichaceae in rectal microbiota. Sci Rep. 2018 Oct 12;8(1):15212. doi: 10.1038/s41598-018-33524-6.
  PMID: 30315206
  citation: Perler BK, Reinhart EM, Montgomery M, Maynard M, Shapiro JM, Belenky P, Chan PA. Evaluation of the Microbiome in Men Taking Pre-exposure Prophylaxis for HIV Prevention. AIDS Behav. 2021 Jul;25(7):2005-2013. doi: 10.1007/s10461-020-03130-7. Epub 2021 Jan 4.
  PMID: 33394167
  responsible party type: Sponsor-Investigator
  investigator affiliation: University of Louisville
  investigator full name: Shirish S Barve
  investigator title: Professor
  mesh term: Dysbiosis
  mesh term: Alcoholism
  sharing ipd: No