Alcohol Use Disorder
Conditions
Brief summary
For this protocol, the investigators plan to collect pilot data to examine the effect of endotoxin on drinking behavior in the human laboratory.
Detailed description
This pilot study is a double-blind, placebo-controlled design, which will compare endotoxin (0.4ng/kg i.v.) to placebo (0.0ng/kg) in non-treatment seeking adults meeting criteria for DSM-5 alcohol use disorders (n=32 total, n=16 per group). Eligibility screening consists of an intake session and a physical exam. Participants meeting eligibility criteria will be randomized to receive a single dose of 0.4ng/kg i.v. endotoxin or placebo during a single laboratory session to evaluate ad-libitum alcohol consumption. During the laboratory session, endotoxin (or placebo) administration will precede a 2-hour alcohol self-administration period. Participants will be scheduled for a follow-up appointment to evaluate drinking behavior. Adverse events are evaluated during the laboratory session and follow-up, and will be tabulated.
Interventions
DRUGEndotoxin
Endotoxin 0.4ng/kg i.v.
Sponsors
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Age 21-65; 2. Able to read and write English; 3. Meets DSM-5 criteria for current (past 6 months) alcohol use disorder; 4. Drinking criteria: Males - Drinks \> 14 drinks per week and exceeds 4 drinks per day at least twice per week; Females -Drinks \> 7 drinks per week and exceeds 3 drinks per day at least twice per week. 5. Must meet drinking criteria during a consecutive 30-day period within the 90 days prior to baseline; 6. Laboratory sessions will be scheduled such that subjects will not have major responsibilities on the following day which might limit drinking during the self-administration session (e.g., job interview, exam). 7. Negative urine pregnancy test for women.
Exclusion criteria
1. Participants with any significant current medical conditions (neurological, cardiovascular \[including hypertension or hypotension: sitting BP \>160/100 or \<90/60mmHg at baseline screening\], endocrine, thyroid, renal, liver), seizures, delirium or hallucinations, or other unstable medical conditions including HIV; 2. Current DSM-5 substance use disorders, other than alcohol or nicotine; 3. A positive test result at intake appointment on urine drug screens conducted for illicit drugs, excluding cannabis; 4. Past 30 day use of psychoactive drugs including anxiolytics and antidepressants; 5. Women who are pregnant or nursing, or fail to use one of the following methods of birth control unless she or partner is surgically sterile or she is postmenopausal (hormone contraceptives \[oral, implant, injection, patch, or ring\], contraceptive sponge, double barrier \[diaphragm or condom plus spermicide\], or IUD); 6. Suicidal, homicidal or evidence of current (past 6-month) severe mental illness such as schizophrenia, bipolar disorder or major depression, or anxiety disorders; 7. Subjects treatment-seeking or who are currently in treatment for alcohol use; 8. Subjects with medical conditions contraindicating alcohol use (e.g., liver enzymes ≥3× normal); 9. Subjects likely to exhibit clinically significant alcohol withdrawal during the study. We will exclude subjects who a) have a history of perceptual distortions, seizures, delirium, or hallucinations upon withdrawal, or b) have a score of \> 8 on the Clinical Institute Withdrawal Assessment scale at intake appointments; 10. Participation within the past 8 weeks in other studies that involve additive blood sampling and/or interventional measures that would be considered excessive in combination with the current application. 11. Subjects \>38 on the Alcohol Use Disorders Identification Test (AUDIT) 12. Subjects with resting pulse \>100 at challenge 13. Subjects with recent (past 2 weeks) acute illness or vaccination 14. Subjects with \>Grade 2 laboratory abnormalities on screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Alcohol Consumption | 120 minutes | Mean mls of alcohol consumed for endotoxin and placebo groups during 120 minute alcohol self-administration session. |
Countries
United States
Participant flow
Pre-assignment details
Participants randomly assigned to endotoxin or placebo prior to the lab session.
Participants by arm
| Arm | Count |
|---|---|
| Endotoxin Endotoxin (0.4ng/kg i.v.) will be administered one time during the laboratory session. | 7 |
| Placebo Administered one time during the laboratory session. | 6 |
| Total | 13 |
Baseline characteristics
| Characteristic | Endotoxin | 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 | 7 Participants | 6 Participants | 13 Participants |
| Marital Status Cohabitating | 0 Participants | 1 Participants | 1 Participants |
| Marital Status Divorced | 0 Participants | 1 Participants | 1 Participants |
| Marital Status Married | 2 Participants | 0 Participants | 2 Participants |
| Marital Status Single | 5 Participants | 4 Participants | 9 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 3 Participants | 5 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 | 3 Participants | 2 Participants | 5 Participants |
| Region of Enrollment United States | 7 participants | 6 participants | 13 participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 6 |
| other Total, other adverse events | 0 / 7 | 0 / 6 |
| serious Total, serious adverse events | 0 / 7 | 0 / 6 |
Outcome results
Primary
Alcohol Consumption
Mean mls of alcohol consumed for endotoxin and placebo groups during 120 minute alcohol self-administration session.
Time frame: 120 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Endotoxin | Alcohol Consumption | 37.57 Milliliters | Standard Deviation 47.27 |
| Placebo | Alcohol Consumption | 50.08 Milliliters | Standard Deviation 37.58 |