Varenicline for Smoking Cessation in Heavy Drinking Smokers

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Stephanie O'Malley, Yale University
ClinicalTrials.gov Identifier:
NCT00860028
First received: March 10, 2009
Last updated: January 28, 2013
Last verified: January 2013
  Purpose

The purpose of this study is to determine whether extended pretreatment with varenicline (Chantix) is more efficacious for smoking cessation than standard pretreatment, how well varenicline is tolerated in heavy drinking smokers, and whether varenicline reduces alcohol consumption.


Condition Intervention Phase
Nicotine Dependence
Smoking
Heavy Drinking
Drug: Varenicline
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Varenicline for Smoking Cessation in Heavy Drinking Smokers

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • Number of Participants Reporting Continuous Smoking Abstinence in the Extended Varenicline Pretreatment Versus Short-term Varenicline Pretreatment Conditions. [ Time Frame: Last 4 weeks of treatment ] [ Designated as safety issue: No ]
    Compares the number of participants who reported no smoking, not even a puff, from the quit date through until the end of treatment (i.e., last 4 weeks of treatment) in the varenicline versus placebo pretreatment conditions.

  • Mean Percentage of Heavy Drinking Days Comparing Participants in the Extended Varenicline Pretreatment Versus Short-term Varenicline Pretreatment Conditions [ Time Frame: First 3 weeks (pretreatment) ] [ Designated as safety issue: No ]
    Compares the mean percentage of heavy drinking days over the 3-week placebo-controlled pretreatment phase comparing participants in the extended varenicline pretreatment versus the short-term varenicline pretreatment conditions. Heavy drinking defined as consuming 4 or more drinks per occasion for women and 5 or more drinks per occasion for men. Drinking in the final week of pretreatment prior to the quit-date is not included because both groups were receiving active varenicline during this period.


Secondary Outcome Measures:
  • Number of Participants Who Reported an Adverse Event in the Varenicline Pretreatment Versus Placebo Pretreatment Conditions [ Time Frame: First 3 weeks (pretreatment) ] [ Designated as safety issue: Yes ]
    Compares the number of participants who reported an adverse event in the extended varenicline pretreatment versus short-term varenicline pretreatment conditions during the 3-week placebo controlled pretreatment phase


Enrollment: 30
Study Start Date: October 2008
Study Completion Date: May 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Extended Varenicline Pretreatment
Arm 1 (Experimental) = 4 weeks varenicline (Chantix) titrated to 1 mg oral tablet twice per day before the smoking quit date followed by 4 weeks varenicline (Chantix) 1 mg oral tablet twice per day treatment.
Drug: Varenicline
Other Name: chantix
Experimental: Short-term Varenicline Pretreatment
Arm 2 (Experimental) = 3 weeks placebo + 1 week varenicline (Chantix)pretreatment + 4 weeks varenicline 1 mg oral tablet twice per day treatment following the smoking quit date.
Drug: Varenicline
Other Name: chantix

Detailed Description:

Smoking rates are elevated among drinkers compared to non-drinkers (Marks et al., 1997). Moreover, there is some evidence that both smokers who drink alcohol are less successful quitting smoking (Leeman, Huffman, & O'Malley, 2007). Thus, identifying interventions that are effective in reducing both smoking and heavy drinking in this population is warranted. Varenicline, a medication recently approved by the FDA, results in smoking cessation rates as high as 50%, significantly better than bupropion or placebo. There is preliminary experimental evidence from both animal and human laboratory research that varenicline reduces alcohol seeking and consumption (McKee, 2008; Steensland et al., 2007).

The typical dose schedule for varenicline involves a 1 week pretreatment phase prior to quitting smoking (Gonzales et al., 2006; Jorenby et al., 2006; Nides et al., 2006). However, greater quit rates have been observed 1 month after using varenicline compared to 1 week. Therefore, it is possible that extended pretreatment with varenicline may also yield better cessation outcomes than the standard 1 week lead in period. This may be particularly true if pretreatment also reduces alcohol consumption prior to the quit attempt.

Thirty regular smokers who drink alcohol heavily will receive open-label varenicline for 5 weeks according to the recommended titration schedule up to 1mg varenicline twice daily. Prior to the smoking quit date, subjects will be randomized to receive either extended pretreatment with varenicline (titration up to 1mg) for 4 weeks or short-term varenicline pretreatment (3 weeks placebo followed by 1 week of varenicline).

The primary aims of the study are to examine: (a) the efficacy of extended varenicline pretreatment for smoking cessation, (b) the safety and tolerability of varenicline in heavy drinking smokers, and (c) the efficacy of varenicline for reducing alcohol consumption in human participants. Effect size estimates for prolonged smoking abstinence and heavy drinking will be generated for a NIH grant application.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Between the ages of 18 and 75.
  2. Smoking 5 or more cigarettes per occasion at least 3 times per week.
  3. Fewer than 3 months of smoking abstinence in the past year.
  4. Motivated to stop smoking.
  5. Report exceeding maximum weekly drinking limits every week in the past 4 weeks and exceeding maximum daily drinking limits on at least 1 occasion in the past 4 weeks. Weekly heavy drinking is defined as 8 or more drinks for women and 15 or more drinks for men. Daily heavy drinking is defined as 4 or more drinks for women and 5 or more drinks for men on an occasion.

Exclusion Criteria:

  1. Exhibit current, clinically significant physical disease or abnormality on the basis of medical history, physical examination, or routine laboratory evaluation
  2. Any unexplained elevations in liver enzymes (i.e., transaminases, bilirubin)
  3. Clinically significant cardiovascular disease
  4. Uncontrolled hypertension
  5. Hepatic or renal impairment
  6. Severe chronic obstructive pulmonary disease
  7. Diabetes mellitus requiring insulin or oral hypoglycemic medications.
  8. Baseline systolic blood pressure higher than 150 mm Hg or diastolic blood pressure higher than 95 mm Hg
  9. History of cancer (except treated basal cell or squamous cell carcinoma of the skin).
  10. History of clinically significant allergic reactions.
  11. Exhibit serious psychiatric illness (i.e., schizophrenia, bipolar disorder, severe major depression, panic disorder, borderline personality disorder, organic mood or mental disorders, or substantial suicide or violence risk) by history or psychological examination)
  12. Have a current diagnosis of DSM-IV drug dependence other than nicotine or alcohol.
  13. Have a current Diagnostic and Statistical Manual Diploma in Social Medicine IV (DSM-IV) diagnosis of alcohol dependence that is clinically severe defined by a) a history of seizures, delirium, or hallucinations during alcohol withdrawal, b) a Clinical Institute Withdrawal Assessment scale (Sullivan et al., 1989) score of > 8, c) report drinking to avoid withdrawal symptoms, or d) have had prior treatment of withdrawal.
  14. Use of another investigational drug within 30 days.
  15. Intention to donate blood or blood products during the treatment phase of the study.
  16. Use of tobacco products other than cigarettes or use of marijuana.
  17. Use of nicotine replacement therapy, clonidine, varenicline, bupropion, or nortriptyline within the month prior to enrollment or intention to use medication that might interfere with study medication.
  18. Body Mass Index (calculated as weight in kilograms divided by the square of height in meters) less than 15 or greater than 38 or weight less than 45 kg.
  19. Females of childbearing potential who are pregnant, nursing, or not practicing effective contraception (oral, injectable, or implantable contraceptives, intrauterine device, or barrier method with spermicide).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00860028

Sponsors and Collaborators
Yale University
Investigators
Principal Investigator: Stephanie S O'Malley, PhD Yale School of Medicine
  More Information

Publications:
Responsible Party: Stephanie O'Malley, Professor, Yale University
ClinicalTrials.gov Identifier: NCT00860028     History of Changes
Other Study ID Numbers: NIAAA-O'Malley-P50AA15632-2009, P50AA015632
Study First Received: March 10, 2009
Results First Received: January 3, 2012
Last Updated: January 28, 2013
Health Authority: United States: Federal Government

Keywords provided by Yale University:
Smoking cessation
Smoking
Tobacco
Varenicline
Alcohol

Additional relevant MeSH terms:
Varenicline
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 19, 2014