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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.
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| varenicline | Experimental | 1 mg BID (2 capsules BID) |
|
| Placebo | Placebo Comparator | 1 mg BID (2 capsules BID) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Varenicline | Drug | 1 mg BID |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| 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). | Study Week 3 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Weeks 3-6 |
| The Percentage of Subjects Abstinent During the Last Month of Treatment (Weeks 3-6). |
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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:
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:
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| Name | Affiliation | Role |
|---|---|---|
| Raye Litten, PhD | National Institute on Alcohol Abuse and Alcoholism (NIAAA) | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Yale University School of Medicine | New Haven | Connecticut | 06511 | United States | ||
| Brown University |
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| ID | Title | Description |
|---|---|---|
| FG000 | Varenicline | 1 mg BID (2 capsules BID) Varenicline: 1 mg BID |
| FG001 | Placebo | 1 mg BID (2 capsules BID) Placebo oral capsule: 1 mg BID |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Varenicline | 1 mg BID (2 capsules BID) Varenicline: 1 mg BID |
| BG001 | Placebo | 1 mg BID (2 capsules BID) Placebo oral capsule: 1 mg BID |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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). | mITT | Posted | Mean | Standard Error | units on a scale | Study Week 3 |
|
Weeks 1 to 6
Definitions and descriptions are consistent with those in clinicaltrials.gov.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Varenicline | 1 mg BID (2 capsules BID) Varenicline: 1 mg BID | 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Seizure | Nervous system disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Health Scientist Administrator | National Institute on Alcohol Abuse and Alcoholism | 301-443-0788 | falkde@mail.nih.gov |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 3, 2017 | Oct 3, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000437 | Alcoholism |
| ID | Term |
|---|---|
| D019973 | Alcohol-Related Disorders |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D000068580 | Varenicline |
| ID | Term |
|---|---|
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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| Placebo oral capsule |
| Drug |
1 mg BID |
|
The percentage of subjects abstinent from alcohol during the last month of treatment (weeks 3-6). |
| Weeks 3-6 |
| 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. | Weeks 3-6 |
| 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. | Study Weeks 3, 4, 5, 6 (assessed weekly during this period) |
| Providence |
| Rhode Island |
| 02912 |
| United States |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Drinks per day | Drinks per day is computed by summing the number of standard drinks consumed during the period of interest divided by the number of days in the period of interest. | Mean | Standard Deviation | drinks/day |
|
| Drinking per drinking day | Drinks per drinking day is computed by summing the number of standard drinks consumed during the period of interest divided by the number of drinking days in the period of interest (i.e., days where the subject drank >0 drinks). This measure differs from the measure, drinks per day, only in the denominator (drinks per day includes all days in the period of interest). | Mean | Standard Deviation | drinks/drinking day |
|
| Percent days abstinent | Mean | Standard Deviation | percent days abstinent |
|
| Percent heavy drinking days | Mean | Standard Deviation | percent heavy drinking days |
|
| Penn Alcohol Craving Scale (PACS) score | The PACS is a five-item self-administered instrument for assessing alcohol craving (Flannery et al-1999). Frequency, intensity, and duration of thoughts about drinking are assessed along with ability to resist drinking. Each item is a Likert scale ranging from 0 to 6. The items are summed to produce a total score ranging from 0 to 30. Higher total scores are indicative of greater craving. | Mean | Standard Deviation | units on a scale |
|
| Current smoker (past week) | Count of Participants | Participants |
|
|
|
| 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. | mITT | Posted | Mean | Standard Error | percentage of heavy drinking days | Weeks 3-6 |
|
|
|
| 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). | mITT | Posted | Count of Participants | Participants | Weeks 3-6 |
|
|
|
| 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. | mITT | Posted | Mean | Standard Error | cigarettes per week | Weeks 3-6 |
|
|
|
| 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. | mITT | Posted | Mean | Standard Error | units on a scale | Study Weeks 3, 4, 5, 6 (assessed weekly during this period) |
|
|
|
| 23 |
| 1 |
| 23 |
| 19 |
| 23 |
| EG001 | Placebo | 1 mg BID (2 capsules BID) Placebo oral capsule: 1 mg BID | 0 | 24 | 0 | 24 | 20 | 24 |
| Abnormal Dreams | Psychiatric disorders | Non-systematic Assessment |
|
| Nasopharyngitis | General disorders | Non-systematic Assessment |
|
| Bright Urine | Renal and urinary disorders | Non-systematic Assessment |
|
| Agitation | Psychiatric disorders | Non-systematic Assessment |
|
| Anxiety | Psychiatric disorders | Non-systematic Assessment |
|
| Gynecological bleeding | Reproductive system and breast disorders | Non-systematic Assessment |
|
| Headache | General disorders | Non-systematic Assessment |
|
| Insomnia | Psychiatric disorders | Non-systematic Assessment |
|
| Blurred Vision | Eye disorders | Non-systematic Assessment |
|
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| D011810 | Quinoxalines |