Alcohol Use Disorder
Conditions
Brief summary
This study is a double-blind, randomized, placebo-controlled, parallel group, two-site study designed to assess the effects of varenicline as compared with placebo on responses to in vivo alcohol cue exposure in the human laboratory setting.
Detailed description
This study is a double-blind, randomized, placebo-controlled, parallel group, two-site study designed to assess the effects of varenicline as compared with placebo on responses to in vivo alcohol cue exposure in the human laboratory setting. After signing informed consent, subjects will be screened for eligibility including medical history, physical examination, vital signs, electrocardiogram (ECG), drinking history by the timeline follow-back (TLFB) method, alcohol breathalyzer test, Clinical Institute Withdrawal Assessment for Alcohol-revised (CIWA), medication use, MINI neuropsychiatric interview, urine toxicology screen, clinical chemistry, response to cue reactivity, and Columbia Suicide Severity Rating Scale (CSSR-S). Women of child-bearting potential will have a pregnancy test. If eligible for the study, subjects will be randomized using a stratified permuted block randomization procedure in an approximate 1:1 ratio (targeting 24 subjects per group - 12 subjects per group per site) to receive either varenicline or placebo for 6 weeks. Any nicotine use versus no use (cigarettes, cigars, chewing tobacco, electronic cigarettes, etc.) in the week before randomization is the stratification variable. Varenicline or matched placebo will be titrated over the first week of the study up the maintenance dose of 1 mg (active) or two capsules (placebo) taken orally BID for an additional 5 weeks. Subjects will be seen in the clinic at screening, at randomization and 6 other times during the study. A final follow-up telephone interview will occur during Week 9 (2 weeks after the end of study visit). After the first two weeks and after five weeks of investigational product administration at Study Week 3 and Study Week 6, respectively, subjects will undergo a cue reactivity paradigm session (HLAB) including 4 individual visual analog scale (VAS) items assessing alcohol craving, 2 VAS items assessing emotional reactivity to picture stimuli, and 2 items assessing emotional manipulation. Immediately after the HLAB session, subjects will view each picture again and record the emotion felt using the Self-Manikin Assessment (SAM).
Interventions
DRUGVarenicline
1 mg BID
DRUGPlacebo oral capsule
1 mg BID
Sponsors
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
To be eligible, the subject must: * Be at least 21 years of age. * Meet the DSM 5 criteria for alcohol use disorder of a least moderate severity (AUD-MS). * Be seeking treatment for AUD and desire a reduction or cessation of drinking. * Be able to verbalize an understanding of the consent form, able to provide written informed consent, verbalize willingness to complete study procedures, able to understand written and oral instructions in English and able to complete the questionnaires required by the protocol. * Agree (if the subject is female and of child bearing potential) to use at least one of the following methods of birth control, unless she is surgically sterile, partner is surgically sterile or she is postmenopausal: 1. oral contraceptives, 2. contraceptive sponge, 3. patch, 4. double barrier (diaphragm/spermicidal or condom/spermicidal), 5. intrauterine contraceptive system, 6. levonorgestrel implant, 7. medroxyprogesterone acetate contraceptive injection, 8. complete abstinence from sexual intercourse, and/or 9. hormonal vaginal contraceptive ring. * Be able to take oral medication and be willing to adhere to the medication regimen. * Complete all assessments required at screening and baseline. * Have a place to live in the 2 weeks prior to randomization and not be at risk that s/he will lose his/her housing in the next 2 months. * Not anticipate any significant problems with transportation arrangements or available time to travel to the study site over the next 2 months. * Not have any unresolved legal problems that could jeopardize continuation or completion of the study. * And others.
Exclusion criteria
* Contact site for additional information
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cue-elicited Craving | Study Week 3 | The primary outcome is cue-elicited alcohol craving, operationalized as the difference in Visual Analog Scale (VAS) craving for alcohol when exposed to an alcohol cue minus the VAS craving for alcohol when exposed to a water cue. The VAS has a minimum value of 0 and maximum value of 20; higher scores indicate more craving (a worse outcome). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Heavy Drinking Days | Weeks 3-6 | The percentage of heavy drinking days during the last month of treatment (weeks 3-6). A heavy drinking day is defined as 4 or more drinks on a single day for females and 5 or more drinks on a single day for males. |
| The Percentage of Subjects Abstinent During the Last Month of Treatment (Weeks 3-6). | Weeks 3-6 | The percentage of subjects abstinent from alcohol during the last month of treatment (weeks 3-6). |
| Cigarettes Smoked Per Week | Weeks 3-6 | The number of cigarettes smoked per week during the last month of treatment (weeks 3-6) computed only among participants who were smokers at baseline (varenicline n=11; placebo n=11). Note: cigarettes smoked per week outcome data was missing for two of the varenicline participants resulting in n=9 available for analysis. |
| Penn Alcohol Craving Scale | Study Weeks 3, 4, 5, 6 (assessed weekly during this period) | Penn Alcohol Craving Scale (higher numbers are indicative of more craving for alcohol); min = 0, max = 30. The measure was assessed at Study Weeks 3, 4, 5, and 6. The reported outcome is the adjusted mean total score across weeks 3-6. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Varenicline 1 mg BID (2 capsules BID)
Varenicline: 1 mg BID | 23 |
| Placebo 1 mg BID (2 capsules BID)
Placebo oral capsule: 1 mg BID | 24 |
| Total | 47 |
Baseline characteristics
| Characteristic | Varenicline | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 44.4 years STANDARD_DEVIATION 11 | 43.7 years STANDARD_DEVIATION 11.5 | 43.1 years STANDARD_DEVIATION 12.1 |
| Current smoker (past week) | 11 Participants | 22 Participants | 11 Participants |
| Drinking per drinking day | 8.5 drinks/drinking day STANDARD_DEVIATION 4.1 | 8.9 drinks/drinking day STANDARD_DEVIATION 4.7 | 9.3 drinks/drinking day STANDARD_DEVIATION 5.2 |
| Drinks per day | 6.9 drinks/day STANDARD_DEVIATION 2.4 | 7.3 drinks/day STANDARD_DEVIATION 2.6 | 7.6 drinks/day STANDARD_DEVIATION 2.7 |
| Penn Alcohol Craving Scale (PACS) score | 18.0 units on a scale STANDARD_DEVIATION 4.5 | 17.8 units on a scale STANDARD_DEVIATION 4.1 | 17.7 units on a scale STANDARD_DEVIATION 3.8 |
| Percent days abstinent | 15.1 percent days abstinent STANDARD_DEVIATION 16.9 | 13.4 percent days abstinent STANDARD_DEVIATION 16.3 | 11.8 percent days abstinent STANDARD_DEVIATION 15.9 |
| Percent heavy drinking days | 66.3 percent heavy drinking days STANDARD_DEVIATION 26.5 | 69.2 percent heavy drinking days STANDARD_DEVIATION 25.3 | 71.9 percent heavy drinking days STANDARD_DEVIATION 24.3 |
| Race/Ethnicity, Customized Race/ethnicity Black | 6 Participants | 8 Participants | 2 Participants |
| Race/Ethnicity, Customized Race/ethnicity Hispanic | 1 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized Race/ethnicity Other | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race/ethnicity White | 16 Participants | 35 Participants | 19 Participants |
| Region of Enrollment United States | 23 participants | 47 participants | 24 participants |
| Sex: Female, Male Female | 9 Participants | 18 Participants | 9 Participants |
| Sex: Female, Male Male | 14 Participants | 29 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 24 |
| other Total, other adverse events | 19 / 23 | 20 / 24 |
| serious Total, serious adverse events | 1 / 23 | 0 / 24 |
Outcome results
Primary
Cue-elicited Craving
The primary outcome is cue-elicited alcohol craving, operationalized as the difference in Visual Analog Scale (VAS) craving for alcohol when exposed to an alcohol cue minus the VAS craving for alcohol when exposed to a water cue. The VAS has a minimum value of 0 and maximum value of 20; higher scores indicate more craving (a worse outcome).
Time frame: Study Week 3
Population: mITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Varenicline | Cue-elicited Craving | 2.1 units on a scale | Standard Error 0.4 |
| Placebo | Cue-elicited Craving | 2.2 units on a scale | Standard Error 0.4 |
Secondary
Cigarettes Smoked Per Week
The number of cigarettes smoked per week during the last month of treatment (weeks 3-6) computed only among participants who were smokers at baseline (varenicline n=11; placebo n=11). Note: cigarettes smoked per week outcome data was missing for two of the varenicline participants resulting in n=9 available for analysis.
Time frame: Weeks 3-6
Population: mITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Varenicline | Cigarettes Smoked Per Week | 47.0 cigarettes per week | Standard Error 7.7 |
| Placebo | Cigarettes Smoked Per Week | 64.0 cigarettes per week | Standard Error 7.6 |
Secondary
Penn Alcohol Craving Scale
Penn Alcohol Craving Scale (higher numbers are indicative of more craving for alcohol); min = 0, max = 30. The measure was assessed at Study Weeks 3, 4, 5, and 6. The reported outcome is the adjusted mean total score across weeks 3-6.
Time frame: Study Weeks 3, 4, 5, 6 (assessed weekly during this period)
Population: mITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Varenicline | Penn Alcohol Craving Scale | 10.8 units on a scale | Standard Error 1.1 |
| Placebo | Penn Alcohol Craving Scale | 10.9 units on a scale | Standard Error 1.1 |
Secondary
Percent Heavy Drinking Days
The percentage of heavy drinking days during the last month of treatment (weeks 3-6). A heavy drinking day is defined as 4 or more drinks on a single day for females and 5 or more drinks on a single day for males.
Time frame: Weeks 3-6
Population: mITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Varenicline | Percent Heavy Drinking Days | 30.7 percentage of heavy drinking days | Standard Error 4.9 |
| Placebo | Percent Heavy Drinking Days | 21.0 percentage of heavy drinking days | Standard Error 5 |
Secondary
The Percentage of Subjects Abstinent During the Last Month of Treatment (Weeks 3-6).
The percentage of subjects abstinent from alcohol during the last month of treatment (weeks 3-6).
Time frame: Weeks 3-6
Population: mITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Varenicline | The Percentage of Subjects Abstinent During the Last Month of Treatment (Weeks 3-6). | 2 Participants |
| Placebo | The Percentage of Subjects Abstinent During the Last Month of Treatment (Weeks 3-6). | 4 Participants |