AddictionPhase 2NCT06015893
Semaglutide Therapy for Alcohol Reduction (STAR)
A Phase 2 study testing Semaglutide in people with Addiction and Alcohol Use Disorder, run by National Institute on Drug Abuse (NIDA) at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 110 years
- Conditions the study is for
- Addiction, Alcohol Use Disorder
- What is being tested?
- Semaglutide
- Type of treatment
- Injection or infusion, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 63 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Oct 2023to 31 Mar 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 110 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- This study will enroll adult individuals with a current diagnosis of AUD. Participants will be recruited without any preference to sex, race, religion, or other social variables, but sociodemographic data will be collected for sample characterization and potential use in the analyses. Since self-reported psychological measures that have been validated in English constitute major part of the study assessments, participants need to be able to speak, read, write, and understand English to be in the study.
- The information needed to assess eligibility will be collected under an IRB-approved NIDA IRP
- screening protocol, led by the Office of the Clinical Director (OCD) at the NIDA IRP to assess
- potential research participants' eligibility for entering clinical protocols. Additional details can be found in the NIDA screening protocol documents. Furthermore, NIH medical records (from other NIH clinical protocols) and outside medical records may also be used, if available, to determine whether participants fulfill the eligibility criteria.
- To be eligible for this study, an individual must meet all of the following criteria:
- At least 18 years old
Show all 11Show fewer
- Alcohol Use Disorder (minimum 2 symptoms on a validated diagnostic tool, e.g., the Mini-International Neuropsychiatric Interview (MINI) or the Structured Clinical Interview for DSM Disorders (SCID))
- Self-reported drinking, according to alcohol Timeline Follow-Back (TLFB), of > 7 drinks per week for females or > 14 drinks per week for males during the 28-day period prior to screening plus at least four days with > 3 drinks for females or > 4 drinks for males during the 28-day period prior to screening
- Most recent Clinical Institute Withdrawal Assessment for Alcohol - revised (CIWA-Ar) score < 10
- Able to speak, read, write, and understand English as demonstrated by ability to understand and sign the NIDA screening protocol consent
- Normal or corrected-to-normal (e.g., wearing glasses or contacts) vision and normal or corrected-to-normal (e.g., with the use of a hearing aid) hearing
Who cannot join
- An individual who meets any of the following criteria will be excluded from enrolling in this study:
- BMI < 23 kg/m^2 or BMI >= 50 kg/m^2
- Evidence of malnutrition as determined by the Nutrition Risk Screening 2002 (NRS-2002)
- Most recent blood tests: creatinine >= 2 mg/dL, eGFR <45 mL/min/1.73 m^2, triglycerides > 500 mg/dl, ALP > 4x the upper limit of normal, clinically abnormal lipase levels per study clinician
- Present diagnosis of diabetes mellitus or blood hemoglobin A1c (HbA1c) >= 6.5 %
- Current (within the past 30 days) use of the following medications with glucose lowering properties: GLP-1 analogues, sulfonylurea, insulin, metformin, thiazolidinediones, dipeptidyl peptidase-4 (DPP-IV) inhibitors, sodium-glucose cotransporter-2 (SGLT-2) inhibitors
Show all 22Show fewer
- Current or prior use of semaglutide or tirzepatide
- Current (within the past 30 days) use of weight-lowering medications
- Current (within the past 30 days) use of FDA-approved pharmacotherapy for AUD (oral or intramuscular naltrexone, acamprosate, disulfiram)
- Current (within the past 30 days) use of medications with known interaction with semaglutide
- Personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
- Known ongoing history of alcohol ketoacidosis, gastroparesis, pancreatitis (either acute or chronic), pancreatic carcinoma, gallbladder disease, jaundice, Mallory-Weiss syndrome (esophageal tears secondary to vomiting), esophageal varices, cirrhosis
- Known history of gastric bypass surgery
- Known history of prior hypersensitivity reaction to semaglutide, any of the product components, or any other GLP-1 analogue
- Known history of suicidal attempts (within the past 24 months) or active suicidal ideation
- Known history of clinically significant vestibular disorders or motion sickness
- Known history of clinically significant noise-induced hearing loss or tinnitus
- Contraindication(s) for brain fMRI
- Unstable cardiovascular conditions (e.g., arrhythmias, clinically significant ECG abnormalities)
- Physical and/or mental health conditions that are clinically unstable, as determined by the study clinicians, including (but not limited to) major depressive disorder or generalized anxiety disorder unstable during the past three months or other psychiatric conditions (e.g., schizophrenia, bipolar disorder) unstable during the past twelve months prior to screening.
- Female who is pregnant, breast-feeding, or intends to become pregnant or is of child-bearing potential and not using a highly effective contraceptive method
- Any other reason or clinical condition that the investigators judge may interfere with study participation and/or be unsafe for a participant
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute on Drug Abuse
Baltimore, Maryland, 21224
About this study
Official title: Semaglutide Therapy for Alcohol Reduction (STAR): A Proof-of-Concept Phase II Clinical Trial
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.
Read more
Objective:
To test if a medication named Semaglutide 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.
Read the detailed description
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 early efficacy and safety/tolerability 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 primary aims will be to determine whether 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). 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 is safe and tolerable, as assessed by the number and severity of adverse events and the proportion of participants who reach the target dose.
- 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
- Conditions
- Addiction, Alcohol Use Disorder
- Being tested
- Take Control, Semaglutide
- Keywords
- Alcohol, Pharmacotherapy, GLP-1, Semaglutide
- Medical subject headings
- Behavior, Addictive, Alcoholism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Take ControlBehavioural
A computer-delivered behavioral therapy derived from the NIAAA s self-help approach, Rethinking Drinking, developed for use in pharmacotherapy trials.
SemaglutideDrug
Weekly subcutaneous (s.c.) injections of semaglutide (or placebo) up to 2.4 mg/week or maximum tolerated dose (MTD).
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Weekly subcutaneous (s.c.) injections of placebo. Receives: Behavioral: Take Control |
| Semaglutide | Experimental | 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. Receives: Behavioral: Take Control; Drug: Semaglutide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine whether semaglutide, compared to placebo, reduces alcohol drinking.
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.
Measured: Difference in number of standard alcohol-containing drinks consumed / week (Drinks Per Week, DPW) from baseline to end of the study.
Secondary outcomes (6)
Determine whether semaglutide reduces brain activity in resting-state and/or task-based fMRI scans.
Differences in fMRI outcomes will demonstrate whether the drug changes brain activity at rest and/or in response to tasks.
Measured: Difference in relevant fMRI measures between the two groups.
Determine whether semaglutide reduces and/or changes food choices in a virtual reality buffet-like laboratory.
Differences in food choices selected will demonstrate whether the drug changes food-seeking behaviors in a population with AUD.
Measured: Difference in food selection in the virtual buffet between the two groups.
Determine whether semaglutide reduces alcohol/food cue-elicited craving assessed in a bar-like laboratory.
Differences in craving scores will demonstrate whether the drug changes cue-reactivity in a population with AUD.
Measured: Difference in alcohol/food craving scores post exposure between the two groups.
Determine whether semaglutide reduces blood Phosphatidylethanol (PEth) levels as a biomarker of alcohol use.
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.
Measured: Difference in blood PEth levels from baseline to end of the study.
Determine whether semaglutide, compared to placebo, reduces other self-reported alcohol-related outcomes.
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.
Measured: 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.
Determine the safety and tolerability of semaglutide in individuals with AUD.
High numbers of serious adverse events negatively reflect a drug s safety and tolerability in a specific patient population.
Measured: Number and severity of adverse events; number of people who reach the target dose.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2023
- Study start17 Oct 2023
- Primary completion31 Mar 2027 (estimated)
- Study completion31 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for AddictionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute on Drug Abuse (NIDA)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Lorenzo Leggio, M.D., Principal investigator, National Institute on Drug Abuse (NIDA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06015893
- Sponsor's protocol ID
- 10001603
- Other IDs
- 001603-DA
- Status last verified
- 31 Aug 2026
- First submitted
- 28 Aug 2023
- Last updated
- 2 Sep 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 26308095Jensen 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.
PubMed 28323117Donnelly 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.
PubMed 21950636Suchankova 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.
PubMed 26080318Marty 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.
PubMed 33424537Chuong 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.
PubMed 37192005Farokhnia 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.
PubMed 36001436Farokhnia 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.
PubMed 35906358Klausen 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.
PubMed 34532853
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Semaglutide Therapy for Alcohol Reduction (STAR): A Proof-of-Concept Phase II Clinical Trial
- ClinicalTrials.gov ID
- NCT06015893
- Acronym / sponsor ID
- 10001603
- Conditions
- Addiction, Alcohol Use Disorder
- Keywords
- Alcohol, Pharmacotherapy, GLP-1, Semaglutide
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 63 participants (actual)
- Lead sponsor
- National Institute on Drug Abuse (NIDA)US National Institutes of Health
- Study start
- 17 Oct 2023 (actual)
- Primary completion
- 31 Mar 2027 (estimated)
- Study completion
- 31 Mar 2027 (estimated)
- First posted
- 29 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 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.
Detailed description
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 early efficacy and safety/tolerability 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 primary aims will be to determine whether 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). 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 is safe and tolerable, as assessed by the number and severity of adverse events and the proportion of participants who reach the target dose.
- 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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Behavioral: Take ControlWeekly subcutaneous (s.c.) injections of placebo. |
| Semaglutide | Experimental | Behavioral: Take Control, Drug: SemaglutideWeekly 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. |
Who may qualify
- Ages
- 18 to 110 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- This study will enroll adult individuals with a current diagnosis of AUD. Participants will be recruited without any preference to sex, race, religion, or other social variables, but sociodemographic data will be collected for sample characterization and potential use in the analyses. Since self-reported psychological measures that have been validated in English constitute major part of the study assessments, participants need to be able to speak, read, write, and understand English to be in the study.
- The information needed to assess eligibility will be collected under an IRB-approved NIDA IRP
- screening protocol, led by the Office of the Clinical Director (OCD) at the NIDA IRP to assess
- potential research participants' eligibility for entering clinical protocols. Additional details can be found in the NIDA screening protocol documents. Furthermore, NIH medical records (from other NIH clinical protocols) and outside medical records may also be used, if available, to determine whether participants fulfill the eligibility criteria.
- At least 18 years old
Key exclusion criteria (22 listed)
- An individual who meets any of the following criteria will be excluded from enrolling in this study:
- BMI < 23 kg/m^2 or BMI >= 50 kg/m^2
- Evidence of malnutrition as determined by the Nutrition Risk Screening 2002 (NRS-2002)
- Most recent blood tests: creatinine >= 2 mg/dL, eGFR <45 mL/min/1.73 m^2, triglycerides > 500 mg/dl, ALP > 4x the upper limit of normal, clinically abnormal lipase levels per study clinician
- Present diagnosis of diabetes mellitus or blood hemoglobin A1c (HbA1c) >= 6.5 %
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Take ControlA computer-delivered behavioral therapy derived from the NIAAA s self-help approach, Rethinking Drinking, developed for use in pharmacotherapy trials. | Behavioural | Placebo, Semaglutide |
| SemaglutideWeekly subcutaneous (s.c.) injections of semaglutide (or placebo) up to 2.4 mg/week or maximum tolerated dose (MTD). | Drug | Semaglutide |
Primary outcome
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.
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.
6 secondary outcomes
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.
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.
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.
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.
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.
Determine the safety and tolerability of semaglutide in individuals with AUD.
Time frame: Number and severity of adverse events; number of people who reach the target dose.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Sep 2026.
- Background: PubMed 26308095Lau 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.
- Background: PubMed 28323117Jensen 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.
- Background: PubMed 21950636Donnelly 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.
- Background: PubMed 26080318Suchankova 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.
- Background: PubMed 33424537Marty 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.
- Background: PubMed 37192005Chuong 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.
- Background: PubMed 36001436Farokhnia 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.
- Background: PubMed 35906358Farokhnia 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.
- Background: PubMed 34532853Klausen 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lorenzo Leggio, M.D. principal investigator
National Institute on Drug Abuse (NIDA)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Semaglutide in people with Addiction and Alcohol Use Disorder, run by National Institute on Drug Abuse (NIDA) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 2 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06015893, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Sep 2026.