Varenicline to Reduce Alcohol Consumption in Heavy Drinkers

NCT00695500 | Completed Phase 1 Results

• 2 other identifiers: 08013708-AA-0137
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This study will determine whether varenicline, a drug that acts on the brain's nicotine receptors and is used to help smokers stop smoking, will have an impact on alcohol self-administration. People between 24 and 60 years of age who regularly consume alcoholic drinks (more than 15 drinks per week for women, and more than 20 drinks per week for men) may be eligible for this study. The study requires five outpatient visits and one overnight hospital admission at the NIH Clinical Center. Participants undergo the following procedures: Visit 1 (outpatient: 4-5 hours)

• Standard assessments, including vital signs measurements, breathalyzer test, blood and urine tests (including pregnancy test for females), questionnaires about mood, symptoms, alcohol use and smoking, if applicable
• Questionnaires about medical and psychological status
• Health assessment and assessment of alcohol drinking behavior Visit 2 (outpatient: 8 hours)
• Standard assessments (see above)
• Computer-Assisted Self-infusion of Ethanol (CASE) session: Subjects will receive a priming intravenous infusion of alcohol. After 25 min, they will be allowed to give themselves additional exposures of alcohol over a period of 2 hours by pressing a button on a computer that controls the infusion pump. Visit 3 (outpatient: 2 hours)
• Standard assessments Visit 4 (outpatient: 8 hours)
• Standard assessments
• Brain functional magnetic resonance imaging scan (MRI). This test uses a magnetic field and radio waves to produce images of the brain. The patient lies on a table that can slide in and out of the scanner, wearing earplugs to muffle loud sounds that occur during the scanning process. Initial pictures are taken of the brain's structure and additional scans measure brain activity while the subject performs simple tasks.
• Alcohol Infusion. Subjects receive an intravenous infusion of alcohol while in the MRI scanner to measure the brain s response to alcohol. Visit 5 (overnight)
• Standard assessments
• Repeat CASE session
• Interview about the subject's experiences participating in the protocol, including any symptoms and urges to drink Visit 6 (outpatient)
• Standard assessments (without blood tests)
• Interview about participation in the study Telephone follow-up After 3 weeks, subjects are called to check on their symptoms and gather information on their drinking and, if applicable, smoking.

Conditions

Alcohol Drinking

Keywords

Varenicline; Alcohol; Alcohol Use

Outcome Measures

Primary Outcomes (1)

• Alcohol Consumption

  Peak Breath Alcohol Concentration during IV alcohol self-administration

  2.5 hr session following 3 weeks of treatment

Secondary Outcomes (1)

• Alcohol Urges

  2.5 hr session following 3 weeks of treatment

Other Outcomes (1)

• BOLD Response to Alcohol Cue

  fMRI session following 2 weeks of treatment

Study Arms (2)

Varenicline

EXPERIMENTAL

Varenicline tablets, 2 mg per day for 3 weeks

Drug: Varenicline

Placebo

PLACEBO COMPARATOR

Placebo tablets, 0 mg per day for 3 weeks

Drug: Placebo

Interventions

Varenicline DRUG

Varenicline tablets, 2 mg per day for 3 weeks

Varenicline

Placebo DRUG

Placebo tablets, 0 mg per day for 3 weeks

Placebo

Eligibility Criteria

• Age: 21 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age 21 to 60 years of age.
• In good health.
• Drink a weekly average of 15 and 20 standard alcoholic drinks (12 gm ethanol/beverage), respectively, for women and men.
• Have a working phone number.

You may not qualify if:

• Currently seeking help for an alcohol problem.
• Subjects with clinically significant alcohol withdrawal.
• More than thirty days of abstinence from alcohol in the ninety days prior to enrollment.
• A positive breath alcohol concentration (BrAC) at the first visit
• A history of major alcohol-related complications at any time, such as pancreatitis.
• Any serious cardiovascular condition or high risk factors, evidenced by any of the following:
• Current or past diagnosis of coronary artery disease (such as ischemia, angina, congestive heart failure, myocardial infarction) or peripheral arterial disease;
• Current or past diagnosis of diabetes, or casual glucose level \> 200 mg/dl;
• Elevated blood pressure (above 160/100) at screening,
• Elevated lipid levels: LDL \> 160 mg/dL, HDL \< 40 mg/dL for males or \< 45 mg/dL for females;
• Clinically significant ECG abnormalities or unstable arrhythmias.
• Contraindication(s) to take the study medication as listed in the package insert.
• Contraindication(s) to take the study medication as listed in the package insert.
• Psychiatric problems requiring clinical attention: a current or past diagnosis of major depression, panic disorder, eating disorders, post traumatic stress disorder, schizophrenia, bipolar disorder, or obsessive compulsive disorder. Individuals who report lifetime (past or current) history of suicidal ideation, suicide attempts or self injury.
• Recent (within the last two months) or regular use of illicit or non-prescribed psycho-active substances such as opiates, benzodiazepines, cocaine, PCP, methamphetamines/other psychostimulants or marijuana.

Sponsors & Collaborators

• Vijay Ramchandani, Ph.D.: lead
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Lachin JM, Matts JP, Wei LJ. Randomization in clinical trials: conclusions and recommendations. Control Clin Trials. 1988 Dec;9(4):365-74. doi: 10.1016/0197-2456(88)90049-9.

  PMID: 3203526 BACKGROUND

• Wei LJ, Lachin JM. Properties of the urn randomization in clinical trials. Control Clin Trials. 1988 Dec;9(4):345-64. doi: 10.1016/0197-2456(88)90048-7.

  PMID: 3203525 BACKGROUND

• Falk DE, Yi HY, Hiller-Sturmhofel S. An epidemiologic analysis of co-occurring alcohol and tobacco use and disorders: findings from the National Epidemiologic Survey on Alcohol and Related Conditions. Alcohol Res Health. 2006;29(3):162-71.

  PMID: 17373404 BACKGROUND

• Gowin JL, Vatsalya V, Westman JG, Schwandt ML, Bartlett S, Heilig M, Momenan R, Ramchandani VA. The Effect of Varenicline on the Neural Processing of Fearful Faces and the Subjective Effects of Alcohol in Heavy Drinkers. Alcohol Clin Exp Res. 2016 May;40(5):979-87. doi: 10.1111/acer.13046. Epub 2016 Apr 8.

  PMID: 27062270 DERIVED

MeSH Terms

Conditions

Alcohol Drinking

Interventions

Varenicline

Condition Hierarchy (Ancestors)

Drinking Behavior; Behavior

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quinoxalines

Limitations and Caveats

The IV alcohol self-administration method may have shown ceiling effects limiting the interpretation of results.

Results Point of Contact

• Title: Ramchandani, Vijay
• Organization: National Institute on Alcohol Abuse and Alcoholism

vijayr@mail.nih.gov

+1 301 402 8527

Study Officials

• Vijay A Ramchandani, Ph.D.

  National Institute on Alcohol Abuse and Alcoholism (NIAAA)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Investigator and Chief, Section on Human Psychopharmacology

Study Record Dates

• First Submitted: June 11, 2008
• First Posted: June 12, 2008
• Study Start: June 1, 2008
• Primary Completion: July 1, 2014
• Study Completion: June 1, 2015
• Last Updated: August 15, 2016
• Results First Posted: August 15, 2016

Record last verified: 2016-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)