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/NCT06015893</url>
    </required_header>
    <id_info>
      <org_study_id>10001603</org_study_id>
      <secondary_id>001603-DA</secondary_id>
      <nct_id>NCT06015893</nct_id>
    </id_info>
    <brief_title>Semaglutide Therapy for Alcohol Reduction (STAR)</brief_title>
    <official_title>Semaglutide Therapy for Alcohol Reduction (STAR): A Proof-of-Concept Phase II Clinical Trial</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>National Institute on Drug Abuse (NIDA)</agency>
        <agency_class>NIH</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>National Institutes of Health Clinical Center (CC)</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>
        Background:&#xD;
  &#xD;
        Alcohol use disorder (AUD) is a problematic pattern of alcohol use accompanied by clinically&#xD;
        significant medical consequences. Medications can help most people reduce their drinking, but&#xD;
        the number is limited, and additional treatment options are needed.&#xD;
  &#xD;
        Objective:&#xD;
  &#xD;
        To test if a medication named Semaglutide is safe and may reduce alcohol drinking in people&#xD;
        with AUD.&#xD;
  &#xD;
        Who can participate?&#xD;
  &#xD;
        All Adults aged 18 or older with AUD might be eligible to participate in the study.&#xD;
  &#xD;
        What will happen during the study?&#xD;
  &#xD;
        Participants will visit the National Institute on Drug Abuse (NIDA) in Baltimore once a week&#xD;
        for about 20 weeks (5 months). Each visit will last between 2 and 6 hours depending on the&#xD;
        tasks scheduled for that visit.&#xD;
  &#xD;
        Participants will be assigned by chance (like flipping a coin) to receive either Semaglutide&#xD;
        or placebo. A placebo looks just like a real drug but contains no medicine.&#xD;
  &#xD;
        The study medication is given as a shot under the skin each week.&#xD;
  &#xD;
        Participants will undergo different tests throughout the study:&#xD;
  &#xD;
        They will give blood, urine, and saliva samples.&#xD;
  &#xD;
        They will engage in self-paced behavioral therapy on a computer.&#xD;
  &#xD;
        They will answer questions about their mood, diet, alcohol drinking and craving, tobacco use,&#xD;
        etc.&#xD;
  &#xD;
        They will taste several sweet liquids and tell their preferences.&#xD;
  &#xD;
        They will sit in a bar-like room and be exposed to cues that might make them feel the urge to&#xD;
        eat food or drink alcohol.&#xD;
  &#xD;
        They will wear a virtual reality headset that creates a cafeteria setting. They will walk the&#xD;
        virtual cafeteria and choose food and drinks from a buffet.&#xD;
  &#xD;
        They will have a functional magnetic resonance imaging (fMRI) scan to take pictures of their&#xD;
        brain. During the scans, participants will be shown pictures of alcohol-containing drinks,&#xD;
        food, and other items.They will perform tasks on a computer screen.&#xD;
  &#xD;
        Participants will have a follow-up visit about 7 weeks after their last shot.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Study Description:&#xD;
  &#xD;
        This study will test the safety/tolerability and early efficacy of subcutaneous (s.c.)&#xD;
        semaglutide at the dose of 2.4 mg/week or maximum tolerated dose (MTD) as a potential new&#xD;
        treatment for alcohol use disorder (AUD).&#xD;
  &#xD;
        Objectives:&#xD;
  &#xD;
        We propose to test safety/tolerability and early efficacy of semaglutide, a glucagon-like&#xD;
        peptide-1 (GLP-1) analogue, as a novel pharmacotherapy to reduce alcohol use and related&#xD;
        measures. This will be a Phase 2a, pilot, proof-of-concept, outpatient study combined with&#xD;
        experimental medicine human laboratory procedures.&#xD;
  &#xD;
        Endpoints:&#xD;
  &#xD;
        The co-primary aims will be to determine whether A) semaglutide is safe and tolerable in&#xD;
        individuals with AUD, as measured by the frequency/severity of adverse events and the&#xD;
        proportion of participants who reach maximum dose, and B) semaglutide reduces alcohol&#xD;
        drinking from baseline to endpoint, as measured by total number of standard&#xD;
        alcohol-containing drinks consumed per week (drinks per week, DPW).&#xD;
  &#xD;
        The following secondary aims will also be examined:&#xD;
  &#xD;
          -  Whether semaglutide reduces other self-reported alcohol-related outcomes (e.g., heavy&#xD;
             drinking days, drinks per drinking days, World Health Organization (WHO) drinking&#xD;
             levels)&#xD;
  &#xD;
          -  Whether semaglutide reduces blood Phosphatidylethanol (PEth) levels as a biomarker of&#xD;
             alcohol use&#xD;
  &#xD;
          -  Whether semaglutide reduces alcohol and/or food cue-elicited craving assessed in a&#xD;
             bar-like laboratory&#xD;
  &#xD;
          -  Whether semaglutide reduces and/or changes food choices in a virtual reality buffet-like&#xD;
             laboratory&#xD;
  &#xD;
          -  Whether semaglutide reduces brain activation during a functional magnetic resonance&#xD;
             imaging (fMRI) scan&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2030</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2030</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Triple (Participant, Care Provider, Investigator)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Determine whether semaglutide, compared to placebo, reduces alcohol drinking.</measure>
      <time_frame>Difference in number of standard alcohol-containing drinks consumed / week (Drinks Per Week, DPW) from baseline to end of the study.</time_frame>
      <description>Recording the difference of alcohol consumption between baseline and end of the study is crucial to understand whether drinking amount/patterns change throughout the study, potentially due to the use of semaglutide.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Determine the safety and tolerability of semaglutide in individuals with AUD.</measure>
      <time_frame>Number and severity of adverse events during the study; number of people who reach the target dose.</time_frame>
      <description>High numbers of severe adverse events negatively reflect a drug s safety and tolerability in a specific patient population.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Determine whether semaglutide, compared to placebo, reduces other self-reported alcohol-related outcomes.</measure>
      <time_frame>Difference in other alcohol-related outcomes (e.g., heavy drinking days, drinks per drinking days, WHO drinking levels) from baseline to end of the study.</time_frame>
      <description>Recording the difference of alcohol consumption between baseline and end of the study is crucial to understand whether drinking amount/patterns change throughout the study, potentially due to the use of semaglutide.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Determine whether semaglutide reduces blood Phosphatidylethanol (PEth) levels as a biomarker of alcohol use.</measure>
      <time_frame>Difference in blood PEth levels from baseline to end of the study.</time_frame>
      <description>Recording the difference of blood PEth levels between baseline and end of the study will provide an objective biomarker of change in alcohol use throughout the study, potentially due to the use of semaglutide.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Determine whether semaglutide reduces alcohol/food cue-elicited craving assessed in a bar-like laboratory.</measure>
      <time_frame>Difference in alcohol/food craving scores post exposure between the two groups.</time_frame>
      <description>Differences in craving scores will demonstrate whether the drug changes cue-reactivity in a population with AUD.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Determine whether semaglutide reduces and/or changes food choices in a virtual reality buffet-like laboratory.</measure>
      <time_frame>Difference in food selection in the virtual buffet between the two groups.</time_frame>
      <description>Differences in food choices selected will demonstrate whether the drug changes food-seeking behaviors in a population with AUD.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Determine whether semaglutide reduces brain activity in resting-state and/or task-based fMRI scans.</measure>
      <time_frame>Difference in relevant fMRI measures between the two groups.</time_frame>
      <description>Differences in fMRI outcomes will demonstrate whether the drug changes brain activity at rest and/or in response to tasks.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">52</enrollment>
    <condition>Addiction</condition>
    <condition>Alcohol Use Disorder</condition>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Weekly subcutaneous (s.c.) injections of placebo.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Semaglutide</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Weekly subcutaneous (s.c.) injections of semaglutide up to 2.4 mg/week or maximum tolerated dose (MTD). Consistent with current recommendations, the dose will be titrated at minimum every four weeks to maximize tolerability and minimize adverse events.</description>
    </arm_group>
    <intervention>
      <intervention_type>Behavioral</intervention_type>
      <intervention_name>Take Control</intervention_name>
      <description>A computer-delivered behavioral therapy derived from the NIAAA s self-help approach, Rethinking Drinking, developed for use in pharmacotherapy trials.</description>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_label>Semaglutide</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Semaglutide</intervention_name>
      <description>Weekly subcutaneous (s.c.) injections of semaglutide (or placebo) up to 2.4 mg/week or maximum tolerated dose (MTD).</description>
      <arm_group_label>Semaglutide</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          -  INCLUSION CRITERIA:&#xD;
  &#xD;
          This study will enroll adult individuals with a current diagnosis of AUD. Participants will&#xD;
          be recruited without any preference to gender, race, religion, or other social variables,&#xD;
          but sociodemographic data will be collected for sample characterization and potential use&#xD;
          in the analyses. Since self-reported psychological measures that have been validated in&#xD;
          English constitute major part of the study assessments, participants need to be able to&#xD;
          speak, read, write, and understand English to be in the study.&#xD;
  &#xD;
          The information needed to assess eligibility will be collected under an IRB-approved NIDA&#xD;
          IRP&#xD;
  &#xD;
          screening protocol, led by the Office of the Clinical Director (OCD) at the NIDA IRP to&#xD;
          assess&#xD;
  &#xD;
          potential research participants eligibility for entering clinical protocols. Additional&#xD;
          details can be found in the NIDA screening protocol documents. Furthermore, NIH medical&#xD;
          records (from other NIH clinical protocols) and outside medical records may also be used,&#xD;
          if available, to determine whether participants fulfill the eligibility criteria.&#xD;
  &#xD;
          To be eligible for this study, an individual must meet all of the following criteria:&#xD;
  &#xD;
            -  At least 18 years old&#xD;
  &#xD;
            -  Alcohol Use Disorder (minimum 2 symptoms on a validated diagnostic tool, e.g., the&#xD;
               Mini-International Neuropsychiatric Interview (MINI) or the Structured Clinical&#xD;
               Interview for DSM Disorders (SCID))&#xD;
  &#xD;
            -  Self-reported drinking, according to alcohol TimeLine FollowBack (TLFB), of &gt; 7 drinks&#xD;
               per week for females or &gt; 14 drinks per week for males during the 28-day period prior&#xD;
               to screening + at least four days with &gt; 3 drinks for females or &gt; 4 drinks for males&#xD;
               during the 28-day period prior to screening&#xD;
  &#xD;
            -  Most recent Clinical Institute Withdrawal Assessment for Alcohol revised (CIWA-Ar)&#xD;
               score &lt; 10&#xD;
  &#xD;
            -  Able to speak, read, write, and understand English as demonstrated by ability to&#xD;
               understand and sign the NIDA screening protocol consent&#xD;
  &#xD;
            -  Normal or corrected-to-normal (e.g., wearing glasses or contacts) vision and normal or&#xD;
               corrected-to-normal (e.g., with the use of a hearing aid) hearing&#xD;
  &#xD;
          EXCLUSION CRITERIA:&#xD;
  &#xD;
          An individual who meets any of the following criteria will be excluded from enrolling in&#xD;
          this study:&#xD;
  &#xD;
            -  BMI &lt; 25 kg/m^2 or BMI &gt;= 50 kg/m^2&#xD;
  &#xD;
            -  Evidence of malnutrition as determined by the Nutrition Risk Screening 2002 (NRS-2002)&#xD;
  &#xD;
            -  Most recent blood tests: creatinine &gt;= 2 mg/dL, eGFR &lt;= 60 mL/min/1.73 m^2,&#xD;
               triglycerides &gt; 500 mg/dl, ALP &gt; 4(SqrRoot) the upper limit of normal, clinically&#xD;
               abnormal lipase levels per study clinician&#xD;
  &#xD;
            -  Present diagnosis of diabetes mellitus or blood hemoglobin A1c (HbA1c) &gt;= 6.5 %&#xD;
  &#xD;
            -  Current (within the past 30 days) use of the following medications with glucose&#xD;
               lowering properties: GLP-1 analogues, sulfonylurea, insulin, metformin,&#xD;
               thiazolidinediones, dipeptidyl peptidase-4 (DPP-IV) inhibitors, sodium-glucose&#xD;
               cotransporter-2 (SGLT-2) inhibitors&#xD;
  &#xD;
            -  Current (within the past 30 days) use of weight-lowering medications&#xD;
  &#xD;
            -  Current (within the past 30 days) use of FDA-approved pharmacotherapy for AUD (oral or&#xD;
               intramuscular naltrexone, acamprosate, disulfiram)&#xD;
  &#xD;
            -  Current (within the past 30 days) use of medications with known interaction with&#xD;
               semaglutide&#xD;
  &#xD;
            -  Personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine&#xD;
               Neoplasia syndrome type 2 (MEN 2)&#xD;
  &#xD;
            -  Known history of alcohol ketoacidosis, gastroparesis, pancreatitis (either acute or&#xD;
               chronic), pancreatic carcinoma, gallbladder disease, jaundice, Mallory-Weiss syndrome&#xD;
               (esophageal tears secondary to vomiting), esophageal varices, cirrhosis&#xD;
  &#xD;
            -  Known history of gastric bypass surgery&#xD;
  &#xD;
            -  Known history of prior hypersensitivity reaction to semaglutide, any of the product&#xD;
               components, or any other GLP-1 analogue&#xD;
  &#xD;
            -  Known history of suicidal attempts (within the past 24 months) or active suicidal&#xD;
               ideation&#xD;
  &#xD;
            -  Known history of vestibular disorders or clinically significant motion sickness&#xD;
  &#xD;
            -  Known history of noise-induced hearing loss or tinnitus&#xD;
  &#xD;
            -  Contraindication(s) for brain fMRI&#xD;
  &#xD;
            -  Unstable cardiovascular conditions (e.g., arrhythmias, clinically significant ECG&#xD;
               abnormalities)&#xD;
  &#xD;
            -  Physical and/or mental health conditions that are clinically unstable, as determined&#xD;
               by the study clinicians, including (but not limited to) major depressive disorder or&#xD;
               generalized anxiety disorder unstable during the past three months or other&#xD;
               psychiatric conditions (e.g., schizophrenia, bipolar disorder) unstable during the&#xD;
               past twelve months prior to screening.&#xD;
  &#xD;
            -  Female who is pregnant, breast-feeding, or intends to become pregnant or is of&#xD;
               child-bearing potential and not using a highly effective contraceptive method&#xD;
  &#xD;
            -  Any other reason or clinical condition that the investigators judge may interfere with&#xD;
               study participation and/or be unsafe for a participant&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>110 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Lorenzo Leggio, M.D.</last_name>
      <role>Principal Investigator</role>
      <affiliation>National Institute on Drug Abuse (NIDA)</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Lisa A Farinelli, Ph.D.</last_name>
      <phone>(443) 740-2082</phone>
      <email>farinellila@mail.nih.gov</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Lorenzo Leggio, M.D.</last_name>
      <phone>(240) 478-1503</phone>
      <email>lorenzo.leggio@nih.gov</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>National Institute on Drug Abuse</name>
        <address>
          <city>Baltimore</city>
          <state>Maryland</state>
          <zip>21224</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Lisa Farinelli</last_name>
        <phone>443-740-2082</phone>
        <email>farinellila@mail.nih.gov</email>
      </contact>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <reference>
      <citation>Lau J, Bloch P, Schaffer L, Pettersson I, Spetzler J, Kofoed J, Madsen K, Knudsen LB, McGuire J, Steensgaard DB, Strauss HM, Gram DX, Knudsen SM, Nielsen FS, Thygesen P, Reedtz-Runge S, Kruse T. Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide. J Med Chem. 2015 Sep 24;58(18):7370-80. doi: 10.1021/acs.jmedchem.5b00726. Epub 2015 Sep 11.</citation>
      <PMID>26308095</PMID>
    </reference>
    <reference>
      <citation>Jensen L, Helleberg H, Roffel A, van Lier JJ, Bjornsdottir I, Pedersen PJ, Rowe E, Derving Karsbol J, Pedersen ML. Absorption, metabolism and excretion of the GLP-1 analogue semaglutide in humans and nonclinical species. Eur J Pharm Sci. 2017 Jun 15;104:31-41. doi: 10.1016/j.ejps.2017.03.020. Epub 2017 Mar 16.</citation>
      <PMID>28323117</PMID>
    </reference>
    <reference>
      <citation>Donnelly D. The structure and function of the glucagon-like peptide-1 receptor and its ligands. Br J Pharmacol. 2012 May;166(1):27-41. doi: 10.1111/j.1476-5381.2011.01687.x.</citation>
      <PMID>21950636</PMID>
    </reference>
    <reference>
      <citation>Suchankova P, Yan J, Schwandt ML, Stangl BL, Caparelli EC, Momenan R, Jerlhag E, Engel JA, Hodgkinson CA, Egli M, Lopez MF, Becker HC, Goldman D, Heilig M, Ramchandani VA, Leggio L. The glucagon-like peptide-1 receptor as a potential treatment target in alcohol use disorder: evidence from human genetic association studies and a mouse model of alcohol dependence. Transl Psychiatry. 2015 Jun 16;5(6):e583. doi: 10.1038/tp.2015.68.</citation>
      <PMID>26080318</PMID>
    </reference>
    <reference>
      <citation>Marty VN, Farokhnia M, Munier JJ, Mulpuri Y, Leggio L, Spigelman I. Long-Acting Glucagon-Like Peptide-1 Receptor Agonists Suppress Voluntary Alcohol Intake in Male Wistar Rats. Front Neurosci. 2020 Dec 23;14:599646. doi: 10.3389/fnins.2020.599646. eCollection 2020.</citation>
      <PMID>33424537</PMID>
    </reference>
    <reference>
      <citation>Chuong V, Farokhnia M, Khom S, Pince CL, Elvig SK, Vlkolinsky R, Marchette RC, Koob GF, Roberto M, Vendruscolo LF, Leggio L. The glucagon-like peptide-1 (GLP-1) analogue semaglutide reduces alcohol drinking and modulates central GABA neurotransmission. JCI Insight. 2023 Jun 22;8(12):e170671. doi: 10.1172/jci.insight.170671.</citation>
      <PMID>37192005</PMID>
    </reference>
    <reference>
      <citation>Farokhnia M, Browning BD, Crozier ME, Sun H, Akhlaghi F, Leggio L. The glucagon-like peptide-1 system is modulated by acute and chronic alcohol exposure: Findings from human laboratory experiments and a post-mortem brain study. Addict Biol. 2022 Sep;27(5):e13211. doi: 10.1111/adb.13211.</citation>
      <PMID>36001436</PMID>
    </reference>
    <reference>
      <citation>Farokhnia M, Fede SJ, Grodin EN, Browning BD, Crozier ME, Schwandt ML, Hodgkinson CA, Momenan R, Leggio L. Differential association between the GLP1R gene variants and brain functional connectivity according to the severity of alcohol use. Sci Rep. 2022 Jul 29;12(1):13027. doi: 10.1038/s41598-022-17190-3.</citation>
      <PMID>35906358</PMID>
    </reference>
    <reference>
      <citation>Klausen MK, Thomsen M, Wortwein G, Fink-Jensen A. The role of glucagon-like peptide 1 (GLP-1) in addictive disorders. Br J Pharmacol. 2022 Feb;179(4):625-641. doi: 10.1111/bph.15677.</citation>
      <PMID>34532853</PMID>
    </reference>
    <verification_date>August 18, 2023</verification_date>
    <study_first_submitted>August 28, 2023</study_first_submitted>
    <study_first_submitted_qc>August 28, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 29, 2023</study_first_posted>
    <last_update_submitted>September 2, 2023</last_update_submitted>
    <last_update_submitted_qc>September 2, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 6, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Alcohol</keyword>
    <keyword>Pharmacotherapy</keyword>
    <keyword>GLP-1</keyword>
    <keyword>Semaglutide</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Alcoholism</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT06015893
  org study id: 10001603
  secondary id: 001603-DA
  nct id: NCT06015893
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  Background:
  
        Alcohol use disorder (AUD) is a problematic pattern of alcohol use accompanied by clinically
        significant medical consequences. Medications can help most people reduce their drinking, but
        the number is limited, and additional treatment options are needed.
  
        Objective:
  
        To test if a medication named Semaglutide is safe and may reduce alcohol drinking in people
        with AUD.
  
        Who can participate?
  
        All Adults aged 18 or older with AUD might be eligible to participate in the study.
  
        What will happen during the study?
  
        Participants will visit the National Institute on Drug Abuse (NIDA) in Baltimore once a week
        for about 20 weeks (5 months). Each visit will last between 2 and 6 hours depending on the
        tasks scheduled for that visit.
  
        Participants will be assigned by chance (like flipping a coin) to receive either Semaglutide
        or placebo. A placebo looks just like a real drug but contains no medicine.
  
        The study medication is given as a shot under the skin each week.
  
        Participants will undergo different tests throughout the study:
  
        They will give blood, urine, and saliva samples.
  
        They will engage in self-paced behavioral therapy on a computer.
  
        They will answer questions about their mood, diet, alcohol drinking and craving, tobacco use,
        etc.
  
        They will taste several sweet liquids and tell their preferences.
  
        They will sit in a bar-like room and be exposed to cues that might make them feel the urge to
        eat food or drink alcohol.
  
        They will wear a virtual reality headset that creates a cafeteria setting. They will walk the
        virtual cafeteria and choose food and drinks from a buffet.
  
        They will have a functional magnetic resonance imaging (fMRI) scan to take pictures of their
        brain. During the scans, participants will be shown pictures of alcohol-containing drinks,
        food, and other items.They will perform tasks on a computer screen.
  
        Participants will have a follow-up visit about 7 weeks after their last shot.
  Study Description:
  
        This study will test the safety/tolerability and early efficacy of subcutaneous (s.c.)
        semaglutide at the dose of 2.4 mg/week or maximum tolerated dose (MTD) as a potential new
        treatment for alcohol use disorder (AUD).
  
        Objectives:
  
        We propose to test safety/tolerability and early efficacy of semaglutide, a glucagon-like
        peptide-1 (GLP-1) analogue, as a novel pharmacotherapy to reduce alcohol use and related
        measures. This will be a Phase 2a, pilot, proof-of-concept, outpatient study combined with
        experimental medicine human laboratory procedures.
  
        Endpoints:
  
        The co-primary aims will be to determine whether A) semaglutide is safe and tolerable in
        individuals with AUD, as measured by the frequency/severity of adverse events and the
        proportion of participants who reach maximum dose, and B) semaglutide reduces alcohol
        drinking from baseline to endpoint, as measured by total number of standard
        alcohol-containing drinks consumed per week (drinks per week, DPW).
  
        The following secondary aims will also be examined:
  
          -  Whether semaglutide reduces other self-reported alcohol-related outcomes (e.g., heavy
             drinking days, drinks per drinking days, World Health Organization (WHO) drinking
             levels)
  
          -  Whether semaglutide reduces blood Phosphatidylethanol (PEth) levels as a biomarker of
             alcohol use
  
          -  Whether semaglutide reduces alcohol and/or food cue-elicited craving assessed in a
             bar-like laboratory
  
          -  Whether semaglutide reduces and/or changes food choices in a virtual reality buffet-like
             laboratory
  
          -  Whether semaglutide reduces brain activation during a functional magnetic resonance
             imaging (fMRI) scan
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Triple (Participant, Care Provider, Investigator)
  measure: Determine whether semaglutide, compared to placebo, reduces alcohol drinking.
  time frame: Difference in number of standard alcohol-containing drinks consumed / week (Drinks Per Week, DPW) from baseline to end of the study.
  description: Recording the difference of alcohol consumption between baseline and end of the study is crucial to understand whether drinking amount/patterns change throughout the study, potentially due to the use of semaglutide.
  measure: Determine the safety and tolerability of semaglutide in individuals with AUD.
  time frame: Number and severity of adverse events during the study; number of people who reach the target dose.
  description: High numbers of severe adverse events negatively reflect a drug s safety and tolerability in a specific patient population.
  measure: Determine whether semaglutide, compared to placebo, reduces other self-reported alcohol-related outcomes.
  time frame: Difference in other alcohol-related outcomes (e.g., heavy drinking days, drinks per drinking days, WHO drinking levels) from baseline to end of the study.
  description: Recording the difference of alcohol consumption between baseline and end of the study is crucial to understand whether drinking amount/patterns change throughout the study, potentially due to the use of semaglutide.
  measure: Determine whether semaglutide reduces blood Phosphatidylethanol (PEth) levels as a biomarker of alcohol use.
  time frame: Difference in blood PEth levels from baseline to end of the study.
  description: Recording the difference of blood PEth levels between baseline and end of the study will provide an objective biomarker of change in alcohol use throughout the study, potentially due to the use of semaglutide.
  measure: Determine whether semaglutide reduces alcohol/food cue-elicited craving assessed in a bar-like laboratory.
  time frame: Difference in alcohol/food craving scores post exposure between the two groups.
  description: Differences in craving scores will demonstrate whether the drug changes cue-reactivity in a population with AUD.
  measure: Determine whether semaglutide reduces and/or changes food choices in a virtual reality buffet-like laboratory.
  time frame: Difference in food selection in the virtual buffet between the two groups.
  description: Differences in food choices selected will demonstrate whether the drug changes food-seeking behaviors in a population with AUD.
  measure: Determine whether semaglutide reduces brain activity in resting-state and/or task-based fMRI scans.
  time frame: Difference in relevant fMRI measures between the two groups.
  description: Differences in fMRI outcomes will demonstrate whether the drug changes brain activity at rest and/or in response to tasks.
  arm group label: Placebo
  arm group type: Placebo Comparator
  description: Weekly subcutaneous (s.c.) injections of placebo.
  arm group label: Semaglutide
  arm group type: Experimental
  description: Weekly subcutaneous (s.c.) injections of semaglutide up to 2.4 mg/week or maximum tolerated dose (MTD). Consistent with current recommendations, the dose will be titrated at minimum every four weeks to maximize tolerability and minimize adverse events.
  intervention type: Behavioral
  intervention name: Take Control
  description: A computer-delivered behavioral therapy derived from the NIAAA s self-help approach, Rethinking Drinking, developed for use in pharmacotherapy trials.
  arm group label: Placebo
  arm group label: Semaglutide
  intervention type: Drug
  intervention name: Semaglutide
  description: Weekly subcutaneous (s.c.) injections of semaglutide (or placebo) up to 2.4 mg/week or maximum tolerated dose (MTD).
  arm group label: Semaglutide
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 110 Years
  healthy volunteers: No
  last name: Lorenzo Leggio, M.D.
  role: Principal Investigator
  affiliation: National Institute on Drug Abuse (NIDA)
  last name: Lisa A Farinelli, Ph.D.
  phone: (443) 740-2082
  email: farinellila@mail.nih.gov
  last name: Lorenzo Leggio, M.D.
  phone: (240) 478-1503
  email: lorenzo.leggio@nih.gov
  facility: 
  status: Recruiting
  contact: 
  country: United States
  citation: Lau J, Bloch P, Schaffer L, Pettersson I, Spetzler J, Kofoed J, Madsen K, Knudsen LB, McGuire J, Steensgaard DB, Strauss HM, Gram DX, Knudsen SM, Nielsen FS, Thygesen P, Reedtz-Runge S, Kruse T. Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide. J Med Chem. 2015 Sep 24;58(18):7370-80. doi: 10.1021/acs.jmedchem.5b00726. Epub 2015 Sep 11.
  PMID: 26308095
  citation: Jensen L, Helleberg H, Roffel A, van Lier JJ, Bjornsdottir I, Pedersen PJ, Rowe E, Derving Karsbol J, Pedersen ML. Absorption, metabolism and excretion of the GLP-1 analogue semaglutide in humans and nonclinical species. Eur J Pharm Sci. 2017 Jun 15;104:31-41. doi: 10.1016/j.ejps.2017.03.020. Epub 2017 Mar 16.
  PMID: 28323117
  citation: Donnelly D. The structure and function of the glucagon-like peptide-1 receptor and its ligands. Br J Pharmacol. 2012 May;166(1):27-41. doi: 10.1111/j.1476-5381.2011.01687.x.
  PMID: 21950636
  citation: Suchankova P, Yan J, Schwandt ML, Stangl BL, Caparelli EC, Momenan R, Jerlhag E, Engel JA, Hodgkinson CA, Egli M, Lopez MF, Becker HC, Goldman D, Heilig M, Ramchandani VA, Leggio L. The glucagon-like peptide-1 receptor as a potential treatment target in alcohol use disorder: evidence from human genetic association studies and a mouse model of alcohol dependence. Transl Psychiatry. 2015 Jun 16;5(6):e583. doi: 10.1038/tp.2015.68.
  PMID: 26080318
  citation: Marty VN, Farokhnia M, Munier JJ, Mulpuri Y, Leggio L, Spigelman I. Long-Acting Glucagon-Like Peptide-1 Receptor Agonists Suppress Voluntary Alcohol Intake in Male Wistar Rats. Front Neurosci. 2020 Dec 23;14:599646. doi: 10.3389/fnins.2020.599646. eCollection 2020.
  PMID: 33424537
  citation: Chuong V, Farokhnia M, Khom S, Pince CL, Elvig SK, Vlkolinsky R, Marchette RC, Koob GF, Roberto M, Vendruscolo LF, Leggio L. The glucagon-like peptide-1 (GLP-1) analogue semaglutide reduces alcohol drinking and modulates central GABA neurotransmission. JCI Insight. 2023 Jun 22;8(12):e170671. doi: 10.1172/jci.insight.170671.
  PMID: 37192005
  citation: Farokhnia M, Browning BD, Crozier ME, Sun H, Akhlaghi F, Leggio L. The glucagon-like peptide-1 system is modulated by acute and chronic alcohol exposure: Findings from human laboratory experiments and a post-mortem brain study. Addict Biol. 2022 Sep;27(5):e13211. doi: 10.1111/adb.13211.
  PMID: 36001436
  citation: Farokhnia M, Fede SJ, Grodin EN, Browning BD, Crozier ME, Schwandt ML, Hodgkinson CA, Momenan R, Leggio L. Differential association between the GLP1R gene variants and brain functional connectivity according to the severity of alcohol use. Sci Rep. 2022 Jul 29;12(1):13027. doi: 10.1038/s41598-022-17190-3.
  PMID: 35906358
  citation: Klausen MK, Thomsen M, Wortwein G, Fink-Jensen A. The role of glucagon-like peptide 1 (GLP-1) in addictive disorders. Br J Pharmacol. 2022 Feb;179(4):625-641. doi: 10.1111/bph.15677.
  PMID: 34532853
  responsible party type: Sponsor
  mesh term: Alcoholism
  sharing ipd: Undecided