Alcohol Use Disorder, Cigarette Smoking
Conditions
Brief summary
This is an early-Phase II human laboratory trial using a randomized, placebo-controlled, dose-ranging design to investigate the effects of semaglutide, a GLP-1 receptor agonist, on alcohol-related outcomes in adults with alcohol use disorder (AUD).
Detailed description
This is an early-Phase II human laboratory trial using a randomized, placebo-controlled, dose-ranging design to investigate the effects of semaglutide, a GLP-1 receptor agonist, on laboratory alcohol responses and consumption, naturalistic alcohol consumption, and weight loss in participants with alcohol use disorder (AUD). Participants will attend weekly visits while semaglutide dosage is increased to 1.0mg over a period of approximately 9-10 weeks. Participants will attend weekly visits for medication or placebo administration. At scheduled intervals, participants will complete 4 laboratory sessions involving alcohol self-administration and alcohol challenge to characterize medication effects on alcohol-related outcomes.
Interventions
DRUGSemaglutide
Semaglutide (subcutaneous)
DRUGSham/placebo
Sham subcutaneous injection
Sponsors
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
University of North Carolina, Chapel Hill
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
Randomized parallel group design.
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Age 21-65 * Meeting DSM-5 criteria for current (past year) alcohol use disorder (with 2-7 symptoms endorsed) and National Institute on Alcohol Abuse and Alcoholism (NIAAA) criteria for current at-risk drinking (i.e., \>7/14 drinks in one week for women/men, with at least two episodes of 4+/5+ drinks in the past 30 days) * Willingness/availability to take study medication and complete study procedures, including attending weekly visits for medication administration, side effect assessments, and glucose monitoring * Willingness to complete laboratory sessions involving alcohol administration * Ability to communicate and read in English
Exclusion criteria
* Reporting past 30-day use of illicit drugs other than cannabis at baseline, or having a positive toxicology screen for illicit drugs other than cannabis at baseline * Meeting past-year criteria for a substance use disorder (with the exception of alcohol, tobacco or mild cannabis use disorder) * Current engagement in alcohol treatments, or currently engaged in intentional efforts to quit alcohol use * Past 30-day use of: Sincalide, Sulfonylureas, insulin and insulin products or other medications that may interact with semaglutide;, or weight control medications * Prior use of semaglutide or other GLP-1 agonists * Known or suspected hypersensitivity to study medication or related products * Lifetime diagnosis of severe mental illness (including schizophrenia and bipolar disorder) * History of suicide attempt, or recent (past 30 day) suicidal ideation, or psychiatric hospitalization in the last 6 months * Current significant medical or neurological illness (based on self-report or medical record) including severe hepatic impairment or cirrhosis, impaired renal function (eGFR \<50ml/min), acute or chronic pancreatitis, gastroparesis, gallbladder disease or cholelithiasis, other severe gastrointestinal disease, heart failure, coronary artery disease, stroke, seizure disorder, or other medical condition that poses a risk for the medication or alcohol administration components of the study (as determined by the MD) * A personal or family history of medullary thyroid cancer or multiple endocrine neoplasia 2A or 2B * Calcitonin greater than or equal to 50 ng/L * Uncontrolled thyroid disease at screening * History of major surgical procedures involving the stomach potentially affecting absorption of trial product (e.g., subtotal and total gastrectomy, sleeve gastrectomy, gastric bypass surgery) * History of Type 1 or Type 2 diabetes, or HbA1c \>6.5% measured at screening * History of diabetic retinopathy, proliferative retinopathy, or maculopathy * History of diabetic ketoacidosis * History or presence of malignant neoplasms within the last 5 years (except basal and squamous cell skin cancer and carcinoma in situ) * Currently nursing, pregnant, anticipating pregnancy in the next 6 months, or not using a highly effective contraceptive method as judged by the MD, and defined as: 1. combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal) 2. progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) 3. intrauterine device 4. intrauterine hormone-releasing system 5. bilateral tubal occlusion 6. vasectomized partner 7. sexual abstinence * Elevation of serum lipase, amylase, direct (conjugated) bilirubin, or alkaline phosphatase (ALP), ALT, or AST) more than 3X the upper limit of normal on baseline bloodwork * Baseline body mass index (BMI) \<23kg/m\^2 * Uncontrolled hypertension or systolic BP \>180 mmHg and/or diastolic BP \>105 mmHg, averaged from three measurements * Plans for travel outside of the local area in the upcoming 12 weeks that would interfere with lab visits during the study period (or other logistic factors that would make it difficult to commit to entire duration of study)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Breath Alcohol Concentration | Baseline (Week 0) to post-medication (Week 8) | Peak breath alcohol concentration following an alcohol self-administration procedure. |
| Change in Alcohol Consumed | Baseline (Week 0) to post-medication (Week 8) | Estimated grams of ethanol consumed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Subjective Sedation (Biphasic Alcohol Effects Scale) | baseline (Week 0) to post-medication (Week 8) | Seven questions from the Biphasic Alcohol Effects Scale used to collect self-reported sedative effects during an alcohol challenge procedure. Possible responses are 0 not at all through 10 extremely. Scale scores range from 0 to 70. Higher scores indicate greater sedative effects. |
| Change in Alcohol Demand (Alcohol Purchase Task) | Baseline (Week 0) to post-treatment (Week 8) | The Alcohol Purchase Task is a 20-question self-report measure which asks participants about the number of drinks they would purchase and consume based at different monetary costs. Intensity scores reflect the number of drinks that would be purchased when cost is zero. |
| Change in Subjective Stimulation (Biphasic Alcohol Effects Scale) | Baseline (Week 0) to post-treatment (Week 8) | Seven questions from the Biphasic Alcohol Effects Scale used to collect self-reported feelings of stimulation during an alcohol challenge procedure. Possible responses are 0-10, 0 being not at all and 10 being extremely. Scale score ranges from 0 to 70. Higher scores indicate greater stimulation effects. |
| Change in Cigarette Demand (Cigarette Purchase Task) | Baseline (Week 0) to Post-medication (Week 8) | Self-report cigarette demand as measured by the Cigarette Purchase Task. Intensity scores reflect the number of cigarettes that would be purchased when cost is zero. |
| Change in Daily Alcohol Use | baseline (Week 0) to study endpoint (Week 10) | Self-reported drinks per day averaged across study week. |
| Change in Daily Cigarette Use | baseline (Week 0) to study endpoint (Week 10) | Self-reported cigarettes per day |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Weight | baseline (Week 0) to study endpoint (Week 10) | Change in Body weight |
| Change in HbA1c | baseline (Week 0) to study endpoint (Week 10) | Hemoglobin A1C (HbA1c) |
| Change in Alcohol Elimination | baseline (Week 0) to post-medication (Week 8) | Rate of alcohol elimination following an alcohol challenge procedure |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Semaglutide Participants will receive semaglutide via subcutaneous injections at escalating doses (0.25 mg to 1.0 mg) over 9 weeks.
Semaglutide: Semaglutide (subcutaneous) | 24 |
| Sham/Placebo Participants will receive sham subcutaneous injections over 9 weeks.
Sham/placebo: Sham subcutaneous injection | 24 |
| Total | 48 |
Baseline characteristics
| Characteristic | Semaglutide | Sham/Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants | 24 Participants | 48 Participants |
| Age, Continuous | 40.6 Years STANDARD_DEVIATION 10.5 | 39.0 Years STANDARD_DEVIATION 10.9 | 39.9 Years STANDARD_DEVIATION 10.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants | 22 Participants | 44 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 4 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 21 Participants | 18 Participants | 39 Participants |
| Region of Enrollment United States | 24 Participants | 24 Participants | 48 Participants |
| Sex: Female, Male Female | 17 Participants | 17 Participants | 34 Participants |
| Sex: Female, Male Male | 7 Participants | 7 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 24 |
| other Total, other adverse events | 22 / 24 | 18 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 |
Outcome results
Primary
Change in Alcohol Consumed
Estimated grams of ethanol consumed.
Time frame: Baseline (Week 0) to post-medication (Week 8)
Population: Participants who completed pre- and post-treatment laboratory self-administration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide | Change in Alcohol Consumed | -32.72 grams | Standard Deviation 27.98 |
| Sham/Placebo | Change in Alcohol Consumed | -6.95 grams | Standard Deviation 24.49 |
Primary
Change in Breath Alcohol Concentration
Peak breath alcohol concentration following an alcohol self-administration procedure.
Time frame: Baseline (Week 0) to post-medication (Week 8)
Population: Participants who completed pre- and post-treatment laboratory self-administration.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide | Change in Breath Alcohol Concentration | -0.034 g/dl | Standard Deviation 0.045 |
| Sham/Placebo | Change in Breath Alcohol Concentration | -0.016 g/dl | Standard Deviation 0.047 |
Secondary
Change in Alcohol Demand (Alcohol Purchase Task)
The Alcohol Purchase Task is a 20-question self-report measure which asks participants about the number of drinks they would purchase and consume based at different monetary costs. Intensity scores reflect the number of drinks that would be purchased when cost is zero.
Time frame: Baseline (Week 0) to post-treatment (Week 8)
Population: Participants with pre- and post-treatment alcohol demand data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide | Change in Alcohol Demand (Alcohol Purchase Task) | -2.91 number of drinks | Standard Deviation 3.73 |
| Sham/Placebo | Change in Alcohol Demand (Alcohol Purchase Task) | -2.90 number of drinks | Standard Deviation 7.82 |
Secondary
Change in Cigarette Demand (Cigarette Purchase Task)
Self-report cigarette demand as measured by the Cigarette Purchase Task. Intensity scores reflect the number of cigarettes that would be purchased when cost is zero.
Time frame: Baseline (Week 0) to Post-medication (Week 8)
Population: Participants who reported cigarette use at baseline and provided pre- and post-treatment cigarette demand data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide | Change in Cigarette Demand (Cigarette Purchase Task) | -2.4 number of cigarettes | Standard Deviation 2.61 |
| Sham/Placebo | Change in Cigarette Demand (Cigarette Purchase Task) | -1.20 number of cigarettes | Standard Deviation 2.17 |
Secondary
Change in Daily Alcohol Use
Self-reported drinks per day averaged across study week.
Time frame: baseline (Week 0) to study endpoint (Week 10)
Population: Participants who have pre- and post- treatment data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide | Change in Daily Alcohol Use | -1.43 daily drinks | Standard Deviation 1.51 |
| Sham/Placebo | Change in Daily Alcohol Use | -0.81 daily drinks | Standard Deviation 2.45 |
Secondary
Change in Daily Cigarette Use
Self-reported cigarettes per day
Time frame: baseline (Week 0) to study endpoint (Week 10)
Population: Participants who reported cigarette use at baseline and have pre- and post-treatment data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide | Change in Daily Cigarette Use | -2.48 daily cigarettes | Standard Deviation 4.22 |
| Sham/Placebo | Change in Daily Cigarette Use | -1.30 daily cigarettes | Standard Deviation 2.1 |
Secondary
Change in Subjective Sedation (Biphasic Alcohol Effects Scale)
Seven questions from the Biphasic Alcohol Effects Scale used to collect self-reported sedative effects during an alcohol challenge procedure. Possible responses are 0 not at all through 10 extremely. Scale scores range from 0 to 70. Higher scores indicate greater sedative effects.
Time frame: baseline (Week 0) to post-medication (Week 8)
Population: Participants with pre- and post-treatment data from an alcohol challenge laboratory session.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide | Change in Subjective Sedation (Biphasic Alcohol Effects Scale) | 0.14 Score on a scale | Standard Deviation 10.69 |
| Sham/Placebo | Change in Subjective Sedation (Biphasic Alcohol Effects Scale) | -3.22 Score on a scale | Standard Deviation 7.89 |
Secondary
Change in Subjective Stimulation (Biphasic Alcohol Effects Scale)
Seven questions from the Biphasic Alcohol Effects Scale used to collect self-reported feelings of stimulation during an alcohol challenge procedure. Possible responses are 0-10, 0 being not at all and 10 being extremely. Scale score ranges from 0 to 70. Higher scores indicate greater stimulation effects.
Time frame: Baseline (Week 0) to post-treatment (Week 8)
Population: Participants with pre- and post-treatment data from an alcohol challenge laboratory session.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide | Change in Subjective Stimulation (Biphasic Alcohol Effects Scale) | .45 Score on a scale | Standard Deviation 12.82 |
| Sham/Placebo | Change in Subjective Stimulation (Biphasic Alcohol Effects Scale) | -1.28 Score on a scale | Standard Deviation 13.49 |
Other Pre-specified
Change in Alcohol Elimination
Rate of alcohol elimination following an alcohol challenge procedure
Time frame: baseline (Week 0) to post-medication (Week 8)
Other Pre-specified
Change in HbA1c
Hemoglobin A1C (HbA1c)
Time frame: baseline (Week 0) to study endpoint (Week 10)
Other Pre-specified
Change in Weight
Change in Body weight
Time frame: baseline (Week 0) to study endpoint (Week 10)