A Novel Human Lab Model for Screening AUD Medications
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|ClinicalTrials.gov Identifier: NCT04249882|
Recruitment Status : Recruiting
First Posted : January 31, 2020
Last Update Posted : June 1, 2021
|First Submitted Date ICMJE||January 24, 2020|
|First Posted Date ICMJE||January 31, 2020|
|Last Update Posted Date||June 1, 2021|
|Actual Study Start Date ICMJE||January 28, 2020|
|Estimated Primary Completion Date||June 20, 2022 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
|Original Primary Outcome Measures ICMJE||Same as current|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title ICMJE||A Novel Human Lab Model for Screening AUD Medications|
|Official Title ICMJE||A Novel Human Laboratory Model for Screening Medications for Alcohol Use Disorder|
|Brief Summary||This study design consists of a randomized, double-blind, placebo-controlled, 3-arm, parallel-group study of naltrexone (50 mg QD) and varenicline (1 mg BID). A total of 108 men and women with current AUD (moderate or severe) and reporting intrinsic motivation to change their drinking, will be randomly assigned to receive naltrexone (50 mg QD), varenicline (1 mg BID) or matched placebo. Post-randomization, all participants will complete an alcohol cue-reactivity paradigm prior to the initial dose of study medication. After a week-long medication titration period, participants will be asked to complete a 7-day practice quit attempt, during which they will have daily virtual visits (phone and online) where they will report on their alcohol use. Additionally, a second cue-reactivity paradigm will be conducted 90 minutes following study drug administration on final day of the practice quit attempt (Day 14).|
Recruitment: Participants will be recruited from the community through online and newspaper advertisements. Campaigns in local buses and print publications (e.g., LA Weekly) will also be implemented. Targeted recruitment will also take place through a lab database of previous study participants who agreed to be contacted for future studies.
Telephone Screen: Individuals who call the lab (in response to flyers and advertisements) expressing interest in the study will receive detailed information about the study procedures, and if they remain interested they will complete a telephone screen performed by a trained research assistant for self-reported inclusion and exclusion criteria. Those who appear eligible will be invited to the laboratory for an initial in-person screening session.
Initial Screening: Prior to conducting any research related procedures, research staff will conduct the informed consent process, which details the procedures to take place during the screening visit. Informed consent will be a three-part process. First, participants will be asked to read and provide verbal consent for breathalyzer. If the breathalyzer is above 0.000, the visit will be stopped and the participant will not be compensated. The participant will be given an opportunity to reschedule the visit for another day. If the breathalyzer test is negative, the written informed consent form will be reviewed and signed by the participant and study staff outlining procedures for the initial screening visit. A second written consent form will be reviewed and signed in the presence of the study physician at the medical screening visit if the participant is found eligible to continue to that visit. At the initial screening visit, subjects will be asked to provide a urine sample to test for drugs of abuse and pregnancy (if female), and will complete a series of questionnaires and interviews (described in detail below) to determine initial eligibility. This visit will take approximately 1 hour. Following the initial in-person screening, the study coordinator will meet with the PI to determine if the participant is eligible to continue to the medical screening based on study inclusion/exclusion criteria.
Medical Screening: Those participants who appear to be eligible after the initial screening visit, will then be scheduled for a second screening visit. This visit will be conducted by the study physician and will start with a breathalyzer test. If the breathalyzer is above 0.000, the visit will be stopped and the participant will not be compensated. The participant will be given an opportunity to reschedule the visit for another day. If the breathalyzer test is negative, the physician will conduct the second written (experimental) consent; medical history interview and physical exam. In addition, a urine sample will be obtained for repeat drug screen and pregnancy tests. The participant will then be accompanied by research personnel to the CTRC for blood specimen collection including Comprehensive Metabolic Panel and Complete Blood Count to evaluate overall health; and EKG to screen for medical conditions that could make study participation medically unsafe. The study physician will review each participant's medical history, vital signs, weight, review of systems, and laboratory tests, including liver function tests (LFTs), drug screen, chemistry screen, and urine pregnancy screen to determine if it is medically safe for the participant to take the study medication. Any subject who is excluded from the study will be compensated for their time in the screening session and will be offered referrals for alcohol treatment in the community.
Randomization and Medication Titration: Participants who are eligible after the physical exam will be randomized to one of three treatment conditions (VAR, NTX, or PLA). Urn randomization will be used to balance the groups by gender, smoking status (as reported on question 1 of the Fagerstrom Test for Nicotine Dependence), and drinking status ('heavy' drinker defined as 28 or more drinks per week for males/14 or more drinks per week for females, or 'very heavy' drinker, defined as 35 or more drinks per week for males/28 or more drinks per week for females). The UCLA Research Pharmacy will manage the blind. The three treatment conditions will not be different in appearance or method of administration. All participants will undergo a week-long medication titration period prior to the onset of the practice quit attempt.
Practice-Quit Attempt: During the practice-quit attempt, participants will be instructed to abstain completely from drinking alcohol during a 7-day practice quit period. This period will begin on Day 8 of study medication dosing. During this period, participants will complete daily virtual visits to report on their drinking, mood and craving for alcohol during the previous day in a daily diary assessment (DDA).
Study Medication: On Day 1, participants will report to the laboratory to complete the alcohol cue-reactivity paradigm and receive their first medication dose under direct observation of study staff. They will receive a 7-day supply of study medication in blister packs with AM and PM dosing clearly distinguished for the titration procedure. After reaching full medication dose at the end of one week, participants will come to the laboratory on Day 8 to begin the practice quit attempt and to take AM dose of study medication daily in the lab under direct observation of study staff. Additionally, on the first day of the practice-quit attempt (Day 8), participants will receive a second 7-day supply of study medication. All study medication will be prepared by the UCLA Research Pharmacy and will be identically matched in appearance (opaque capsules with 50 mg of riboflavin to aid in medication compliance procedures) and the medication labels will not reveal the drug identity.
Alcohol Cue Reactivity Sessions (CR): Randomized participants will complete a cue-exposure paradigm at two time points during the study, once on Day 1 prior to ingesting the first dose of study medication, and again on Day 14, approximately 90 minutes after study drug administration. Alcohol cue exposure will follow well-established experimental procedures. Sessions will begin with a 3-minute relaxation period. Participants will then hold and smell a glass of water for 3 minutes to control for the effects of simple exposure to any potable liquid. Next, participants will hold and smell a glass of their preferred alcoholic beverage for 3 minutes. Order is not counterbalanced because of carryover effects that are known to occur. Participants (who are smokers) will be allowed a smoke break immediately prior to the CR assessment. After every 3 minutes of exposure, participants will rate their urge to drink on the Alcohol Urge Questionnaire (AUQ) and their mood on the Profile of Mood States (POMS). AUQ score (alcohol minus water) is the primary outcome for the CR.
Brief Counseling Session: All participants will meet with a trained study counselor briefly after the second cue exposure session on Day 14 to discuss their responses to the alcohol cues and discuss local treatment options. The counselor will begin by introducing him/herself and thanking the participant for his/her participation. He/she will continue by providing the participant with feedback on their responses on various individual difference measures (drinking patterns, severity of AUD diagnosis, family history, CIWA, depression, and other drug use). The counselor will probe for participants' attitudes towards these responses and diagnoses, and provide both informational and emotional support. Next, the counselor will go over the participant's history of alcohol treatment, in order to identify potential barriers to treatment access. He/she will discuss local treatment options with the participant, including the participant's primary care provider, self-help groups, and the UCLA Psychology Clinic. Lastly, the counselor will go over the "Rethinking Drinking" pamphlet with the participant, pointing out specific treatment options discussed in the session, and will address any questions or concerns.
|Study Type ICMJE||Interventional|
|Study Phase ICMJE||Phase 2|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Randomized, double-blind, placebo-controlled, 3-arm, parallel-group study of naltrexone (50 mg QD) and varenicline (1 mg BID).Masking: Triple (Participant, Care Provider, Investigator)
The study team, medical personnel, and participants will be blind to drug condition.Primary Purpose: Treatment
|Condition ICMJE||Alcohol Use Disorder|
|Study Arms ICMJE||
|Publications *||Ho D, Towns B, Grodin EN, Ray LA. A novel human laboratory model for screening medications for alcohol use disorder. Trials. 2020 Nov 23;21(1):947. doi: 10.1186/s13063-020-04842-w.|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE
|Original Estimated Enrollment ICMJE||Same as current|
|Estimated Study Completion Date ICMJE||August 31, 2022|
|Estimated Primary Completion Date||June 20, 2022 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages ICMJE||21 Years to 65 Years (Adult, Older Adult)|
|Accepts Healthy Volunteers ICMJE||No|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT04249882|
|Other Study ID Numbers ICMJE||19-001735
R21AA027180 ( U.S. NIH Grant/Contract )
|Has Data Monitoring Committee||No|
|U.S. FDA-regulated Product||
|IPD Sharing Statement ICMJE||
|Responsible Party||Lara Ray, PhD, University of California, Los Angeles|
|Study Sponsor ICMJE||University of California, Los Angeles|
|Collaborators ICMJE||National Institute on Alcohol Abuse and Alcoholism (NIAAA)|
|PRS Account||University of California, Los Angeles|
|Verification Date||May 2021|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP