Human Laboratory Study Of Varenicline in Smokers

• ClinicalTrials.gov Identifier: NCT00709696
• Recruitment Status: Completed
• First Posted: July 3, 2008
• Results First Posted: December 27, 2017
• Last Update Posted: December 27, 2017
• Sponsor: University of Minnesota
• Collaborators: National Institute on Drug Abuse (NIDA); Pfizer
• Information provided by (Responsible Party): University of Minnesota

Study Description

Brief Summary:

The purpose of this study is to test the ways that a drug called varenicline helps smokers to quit smoking. Varenicline is also called Chantix® and is approved by the United States Food and Drug Administration (FDA) to help people quit smoking. We will test how varenicline works by having you quit smoking and complete tasks that assess how you think and feel. We predict that varenicline help reduce anxiety, improve attention and concentration, and reduce how satisfying cigarettes are.

Condition or disease	Intervention/treatment	Phase
Nicotine Dependence	Drug: Placebo; Drug: Varenicline	Not Applicable

Detailed Description:

The purpose of this study is to understand the therapeutic mechanisms of varenicline, a novel nicotinic analogue, through focused measures of potential psychological and physiological mediators. Varenicline is an FDA-approved pharmacotherapy for smoking cessation that is believed to provide relief from craving and withdrawal through agonism and antagonism of some central nervous system nicotinic acetylcholinergic receptors. However, no controlled studies have established the physiological and psychological processes that mediate the efficacy of varenicline in humans. The main goal of the proposed pilot study is to evaluate and compare the effects of varenicline on subjective, cognitive, and physiological outcomes, using a randomized, placebo-controlled, double-blind between-groups design. The study will combine both brief clinical trial methodology with human laboratory approaches. A secondary goal is to validate the utility of the laboratory paradigms for the identification of future smoking cessation agents.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 7 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Other
• Official Title: Human Laboratory Study Of Varenicline in Smokers
• Study Start Date: April 2008
• Actual Primary Completion Date: December 2009
• Actual Study Completion Date: December 2009

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: 1; Placebo Varenicline	Drug: Placebo; Days 1 - 3 (0.5 mg tablet, q.d.), Days 4 - 7 (0.5 mg tablet, b.i.d.), and Day 8 - 21 (1 mg tablet, b.i.d.).; Other Name: Chantix
Active Comparator: 2; Varenicline	Drug: Varenicline; Days 1 - 3 (0.5 mg tablet, q.d.), Days 4 - 7 (0.5 mg tablet, b.i.d.), and Day 8 - 21 (1 mg tablet, b.i.d.).; Other Name: Chantix

Outcome Measures

Primary Outcome Measures :

1. Nicotine Withdrawal Scale [ Time Frame: 21 days ]
   Scale is equal to days subject did not smoke Scale is 0-5 0 being no days 5 being did not quit at all

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1.1. Who. Subjects will be women and men between the ages of 18 and 40 who have smoked at least 10 cigarettes per day for at least 1 year. They will respond to requests in the public media for individuals who are interested in quitting smoking.

1.2. Total sample/Number per group. The total randomized sample size will equal 20 subjects, equally distributed across the two medication groups.

1.3. Inclusion Criteria.

1. 18 years to 60 years.
2. Smoke Marlboro Lights (This criterion was selected to reduce inter-subject variation in response variables as has been done in many human laboratory studies of smoking behavior. Over 40% of all smokers smoke some type of the Marlboro brand of cigarette (Substance Abuse and Mental Health Services Administration, 2005). Based on telephone screen data for 767 subjects collected at TURC, Marlboro Light cigarettes are the most common type of Marlboro smoked in our sampling population (158/252 Marlboro users [63%]). Therefore, we have decided to only enroll those smoking Marlboro Light cigarettes, non-menthol).
3. Smoked at least 10 cigarettes/day for at least 1 year.
4. English speaking and reading.

5. Females who are of childbearing potential must practice effective contraception and meet the following criteria:

   1. Are instructed to avoid pregnancy through 30 days after the last dose of study medication.
   2. Have a negative urine pregnancy test at baseline.
   3. Agree to use of the birth control methods listed: an oral contraceptive agent, an intrauterine device (IUD), an implantable contraceptive (e.g., Norplant), or an injectable contraceptive (e.g., Depo-Provera) for at least one month prior to entering the study and will continue its use through at least 30 days after the last dose of the study medication. A barrier method of contraception (e.g., condom or diaphragm with spermicide) while participating in the study and 30 days after the last dose of study medication.
6. Willingness to not use illicit drugs during study period including marijuana.

Exclusion Criteria:

1. Concurrent use of tobacco products (other than cigarettes) or nicotine products.
2. Medications that might affect the outcome measures of nicotine reward, cognition, anxiety, and stress will also be a basis for exclusion. These medications include psychotropic drugs (i.e., anti-psychotic, anti-depressant, anti-anxiety, or stimulant), anti- hypertensive agents (e.g., beta-blockers), and other drugs that can influence the outcome domains.
3. History of kidney disease or renal impairment since varenicline is primarily excreted by the kidney and thus such patients are vulnerable to increased and potentially toxic levels of varenicline.
4. Treatment for drug or alcohol dependence during the last year, or evidence of alcohol abuse so severe that the patient is judged potentially unable to comply with the protocol.
5. Suicidal or homicidal ideation.
6. History of bipolar disorder, schizophrenia, schizoaffective disorder, attention deficit disorder, or attention deficit hyperactivity disorder.
7. Current major depression or anxiety disorder.
8. Pregnant or lactating or planning pregnancy during treatment period.
9. Having plans to leave the immediate geographical area within 2 months.
10. Unwillingness or inability to give written informed consent.

Contacts and Locations

Locations

United States, Minnesota

Tobacco Use Research Center

Minneapolis, Minnesota, United States, 55414

Sponsors and Collaborators

University of Minnesota

National Institute on Drug Abuse (NIDA)

Pfizer

Investigators

• Principal Investigator: Marc E Mooney, Ph.D.; University of Minnesota
• Study Director: Andrew Oliver, B.A.; University of Minnesota

More Information

Publications:

Tonstad S, Tønnesen P, Hajek P, Williams KE, Billing CB, Reeves KR; Varenicline Phase 3 Study Group. Effect of maintenance therapy with varenicline on smoking cessation: a randomized controlled trial. JAMA. 2006 Jul 5;296(1):64-71.

Oncken C, Gonzales D, Nides M, Rennard S, Watsky E, Billing CB, Anziano R, Reeves K. Efficacy and safety of the novel selective nicotinic acetylcholine receptor partial agonist, varenicline, for smoking cessation. Arch Intern Med. 2006 Aug 14-28;166(15):1571-7.

Nides M, Oncken C, Gonzales D, Rennard S, Watsky EJ, Anziano R, Reeves KR. Smoking cessation with varenicline, a selective alpha4beta2 nicotinic receptor partial agonist: results from a 7-week, randomized, placebo- and bupropion-controlled trial with 1-year follow-up. Arch Intern Med. 2006 Aug 14-28;166(15):1561-8.

Jorenby DE, Hays JT, Rigotti NA, Azoulay S, Watsky EJ, Williams KE, Billing CB, Gong J, Reeves KR; Varenicline Phase 3 Study Group. Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial. JAMA. 2006 Jul 5;296(1):56-63. Erratum in: JAMA. 2006 Sep 20;296(11):1355.

Gonzales D, Rennard SI, Nides M, Oncken C, Azoulay S, Billing CB, Watsky EJ, Gong J, Williams KE, Reeves KR; Varenicline Phase 3 Study Group. Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial. JAMA. 2006 Jul 5;296(1):47-55.

Nakamura M, Oshima A, Fujimoto Y, Maruyama N, Ishibashi T, Reeves KR. Efficacy and tolerability of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, in a 12-week, randomized, placebo-controlled, dose-response study with 40-week follow-up for smoking cessation in Japanese smokers. Clin Ther. 2007 Jun;29(6):1040-56.

Tsai ST, Cho HJ, Cheng HS, Kim CH, Hsueh KC, Billing CB Jr, Williams KE. A randomized, placebo-controlled trial of varenicline, a selective alpha4beta2 nicotinic acetylcholine receptor partial agonist, as a new therapy for smoking cessation in Asian smokers. Clin Ther. 2007 Jun;29(6):1027-39.

Williams KE, Reeves KR, Billing CB Jr, Pennington AM, Gong J. A double-blind study evaluating the long-term safety of varenicline for smoking cessation. Curr Med Res Opin. 2007 Apr;23(4):793-801.

Aubin HJ, Bobak A, Britton JR, Oncken C, Billing CB Jr, Gong J, Williams KE, Reeves KR. Varenicline versus transdermal nicotine patch for smoking cessation: results from a randomised open-label trial. Thorax. 2008 Aug;63(8):717-24. doi: 10.1136/thx.2007.090647. Epub 2008 Feb 8.

Niaura R, Hays JT, Jorenby DE, Leone FT, Pappas JE, Reeves KR, Williams KE, Billing CB Jr. The efficacy and safety of varenicline for smoking cessation using a flexible dosing strategy in adult smokers: a randomized controlled trial. Curr Med Res Opin. 2008 Jul;24(7):1931-41. doi: 10.1185/03007990802177523 . Epub 2008 May 29.

Nides M, Glover ED, Reus VI, Christen AG, Make BJ, Billing CB Jr, Williams KE. Varenicline versus bupropion SR or placebo for smoking cessation: a pooled analysis. Am J Health Behav. 2008 Nov-Dec;32(6):664-75. doi: 10.5555/ajhb.2008.32.6.664.

Stapleton JA, Watson L, Spirling LI, Smith R, Milbrandt A, Ratcliffe M, Sutherland G. Varenicline in the routine treatment of tobacco dependence: a pre-post comparison with nicotine replacement therapy and an evaluation in those with mental illness. Addiction. 2008 Jan;103(1):146-54. Epub 2007 Nov 19.

• Responsible Party: University of Minnesota
• ClinicalTrials.gov Identifier: NCT00709696
• Other Study ID Numbers: 0702M02324; K01DA019446 ( U.S. NIH Grant/Contract ); DPMCDA ( Other Identifier: NIDA )
• First Posted: July 3, 2008
• Results First Posted: December 27, 2017
• Last Update Posted: December 27, 2017
• Last Verified: December 2017

Keywords provided by University of Minnesota:

Tobacco; nicotine; smoking; varenicline; human laboratory study; stress tolerance; startle response; cognitive assessment; progressive ratio

Additional relevant MeSH terms:

Tobacco Use Disorder; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Varenicline; Nicotinic Agonists; Cholinergic Agonists; Cholinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs