The Effect of Naltrexone and Varenicline on Alcohol-Mediated Smoking Lapse

• Sponsor: Yale University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00773422
• Collaborator: National Institute on Alcohol Abuse and Alcoholism (NIAAA) (NIH)
• Enrollment: 30
• Location: 1
• Arms: 3
• Duration (Months): 106
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to examine how medications thought to attenuate the effects of alcohol (naltrexone) and smoking cessation medications (varenicline) affect the ability to resist smoking and also subsequent ad-lib smoking, following a low-dose alcohol priming drink, in non-treatment seeking alcohol-drinking daily smokers.

Condition or Disease	Intervention/Treatment	Phase
Smoking	Drug: naltrexone; Drug: varenicline; Drug: placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: The Effect of Naltrexone and Varenicline on Alcohol-Mediated Smoking Lapse
• Study Start Date: Jan 1, 2008
• Actual Primary Completion Date: Nov 1, 2016
• Actual Study Completion Date: Nov 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: naltrexone + varenicline naltrexone (25mg) + varenicline (2mg)	Drug: naltrexone; 25 mg/day, with 1-week lead-in medication period. The starting dose is 0 mg/day for days 1-3, followed by 12.5mg/day for day 4, followed by 25mg/day for days 5-7, plus during the laboratory session (day 8).; Drug: varenicline; 2mg/day, with 1-week lead-in medication period. The starting dose is 0.5mg/day for days 1-2, followed by 0.5mg twice daily for days 3-5, followed by 1.0 mg twice daily for days 6-7, plus during the laboratory session (day 8).; Other Names: Chantix
Experimental: varenicline varenicline 2mg	Drug: varenicline; 2mg/day, with 1-week lead-in medication period. The starting dose is 0.5mg/day for days 1-2, followed by 0.5mg twice daily for days 3-5, followed by 1.0 mg twice daily for days 6-7, plus during the laboratory session (day 8).; Other Names: Chantix
Placebo Comparator: placebo placebo control	Drug: placebo; placebo

Outcome Measures

Primary Outcome Measures

1. Latency to Initiate Ad-lib Smoking Session [day 8]

   Time to smoking during the smoking delay task. Smoking delay task occurred on day 8 of the study. Range of time delay is 0 minutes to 50 minutes.

Secondary Outcome Measures

1. Number of Cigarettes Smoked During the Ad-lib Period [day 8]

   Number of cigarettes smoked during the ad libitum phase of the smoking delay task. Task occurred on day 8 of the study.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• ages 21-55

• ability to read and write in English

• alcohol-drinking smokers

Exclusion Criteria:

• any significant current medical conditions that would contraindicate smoking

• current DSM-IV abuse or dependence of other substances, other than nicotine dependence or alcohol abuse.

• positive test result at intake appointments on urine drug screens conducted for opiates, cocaine, or benzodiazepines

• women who are pregnant or nursing

• suicidal, homicidal or evidence of current severe mental illness

• participants prescribed any psychotropic drug in the 30 days prior to study enrollment

• blood donation within the past 6 weeks

• individuals seeking treatment for smoking cessation or drinking or have attempted to quit smoking or drinking within the past 3 months

• specific exclusion for administration of naltrexone not specified above including chronic pain conditions necessitating opioid treatment, and evidence of significant hepatocellular injury as evidenced by SGOT or SGPT > 3x normal or elevated bilirubin

• known allergy to varenicline or taking H2blockers (e.g., Cimetidine)

• participation within the past 8 weeks in other studies that involve additive blood sampling and/or interventional measures that would be considered excessive in combination with the current protocol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale Center for Clinical Investigation, Yale University	New Haven	Connecticut	United States	06519

Sponsors and Collaborators

• Yale University
• National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Investigators

• Principal Investigator: Sherry A McKee, PhD, Yale University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sherry McKee, Associate Professor of Psychiatry, Yale University
• ClinicalTrials.gov Identifier: NCT00773422
• Other Study ID Numbers: HIC0710003188; P50AA015632
• First Posted: Oct 16, 2008
• Last Update Posted: Apr 23, 2018
• Last Verified: Mar 1, 2018

• Keywords provided by Sherry McKee, Associate Professor of Psychiatry, Yale University: smoking lapse behavior; smoking cessation; varenicline; naltrexone; medication effect on smoking lapse behavior
• Additional relevant MeSH terms: Naltrexone; Varenicline

Study Results

Participant Flow

Arm/Group Title	Naltrexone + Varenicline	Varenicline	Placebo
Arm/Group Description	naltrexone (25mg) + varenicline (2mg) naltrexone: 25 mg/day, with 1-week lead-in medication period. The starting dose is 0 mg/day for days 1-3, followed by 12.5mg/day for day 4, followed by 25mg/day for days 5-7, plus during the laboratory session (day 8). varenicline: 2mg/day, with 1-week lead-in medication period. The starting dose is 0.5mg/day for days 1-2, followed by 0.5mg twice daily for days 3-5, followed by 1.0 mg twice daily for days 6-7, plus during the laboratory session (day 8).	varenicline 2mg varenicline: 2mg/day, with 1-week lead-in medication period. The starting dose is 0.5mg/day for days 1-2, followed by 0.5mg twice daily for days 3-5, followed by 1.0 mg twice daily for days 6-7, plus during the laboratory session (day 8).	placebo control placebo: placebo
Period Title: Overall Study
STARTED	11	9	10
COMPLETED	11	9	10
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Naltrexone + Varenicline	Varenicline	Placebo	Total
Arm/Group Description	naltrexone (25mg) + varenicline (2mg) naltrexone: 25 mg/day, with 1-week lead-in medication period. The starting dose is 0 mg/day for days 1-3, followed by 12.5mg/day for day 4, followed by 25mg/day for days 5-7, plus during the laboratory session (day 8). varenicline: 2mg/day, with 1-week lead-in medication period. The starting dose is 0.5mg/day for days 1-2, followed by 0.5mg twice daily for days 3-5, followed by 1.0 mg twice daily for days 6-7, plus during the laboratory session (day 8).	varenicline 2mg varenicline: 2mg/day, with 1-week lead-in medication period. The starting dose is 0.5mg/day for days 1-2, followed by 0.5mg twice daily for days 3-5, followed by 1.0 mg twice daily for days 6-7, plus during the laboratory session (day 8).	placebo control placebo: placebo	Total of all reporting groups
Overall Participants	11	9	10	30
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	29.91 (8.99)	37.67 (10.85)	33.20 (9.73)	33.33 (10.71)
Sex: Female, Male (Count of Participants)
Female	2 18.2%	2 22.2%	2 20%	6 20%
Male	9 81.8%	7 77.8%	8 80%	24 80%

Outcome Measures

1. Primary Outcome

Title	Latency to Initiate Ad-lib Smoking Session
Description	Time to smoking during the smoking delay task. Smoking delay task occurred on day 8 of the study. Range of time delay is 0 minutes to 50 minutes.
Time Frame	day 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Naltrexone + Varenicline	Varenicline	Placebo
Arm/Group Description	naltrexone (25mg) + varenicline (2mg) naltrexone: 25 mg/day, with 1-week lead-in medication period. The starting dose is 0 mg/day for days 1-3, followed by 12.5mg/day for day 4, followed by 25mg/day for days 5-7, plus during the laboratory session (day 8). varenicline: 2mg/day, with 1-week lead-in medication period. The starting dose is 0.5mg/day for days 1-2, followed by 0.5mg twice daily for days 3-5, followed by 1.0 mg twice daily for days 6-7, plus during the laboratory session (day 8).	varenicline 2mg varenicline: 2mg/day, with 1-week lead-in medication period. The starting dose is 0.5mg/day for days 1-2, followed by 0.5mg twice daily for days 3-5, followed by 1.0 mg twice daily for days 6-7, plus during the laboratory session (day 8).	placebo control placebo: placebo
Measure Participants	11	9	10
Mean (Standard Error) [minutes]	28.134 (5.328)	45.861 (6.238)	21.737 (6.043)

2. Secondary Outcome

Title	Number of Cigarettes Smoked During the Ad-lib Period
Description	Number of cigarettes smoked during the ad libitum phase of the smoking delay task. Task occurred on day 8 of the study.
Time Frame	day 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Naltrexone + Varenicline	Varenicline	Placebo
Arm/Group Description	naltrexone (25mg) + varenicline (2mg) naltrexone: 25 mg/day, with 1-week lead-in medication period. The starting dose is 0 mg/day for days 1-3, followed by 12.5mg/day for day 4, followed by 25mg/day for days 5-7, plus during the laboratory session (day 8). varenicline: 2mg/day, with 1-week lead-in medication period. The starting dose is 0.5mg/day for days 1-2, followed by 0.5mg twice daily for days 3-5, followed by 1.0 mg twice daily for days 6-7, plus during the laboratory session (day 8).	varenicline 2mg varenicline: 2mg/day, with 1-week lead-in medication period. The starting dose is 0.5mg/day for days 1-2, followed by 0.5mg twice daily for days 3-5, followed by 1.0 mg twice daily for days 6-7, plus during the laboratory session (day 8).	placebo control placebo: placebo
Measure Participants	11	9	10
Mean (Standard Error) [cigarettes]	1.283 (0.283)	0.959 (0.331)	2.23 (0.331)

Adverse Events

Arm/Group Title	Naltrexone + Varenicline		Varenicline		Placebo
Arm/Group Description	naltrexone (25mg) + varenicline (2mg) naltrexone: 25 mg/day, with 1-week lead-in medication period. The starting dose is 0 mg/day for days 1-3, followed by 12.5mg/day for day 4, followed by 25mg/day for days 5-7, plus during the laboratory session (day 8). varenicline: 2mg/day, with 1-week lead-in medication period. The starting dose is 0.5mg/day for days 1-2, followed by 0.5mg twice daily for days 3-5, followed by 1.0 mg twice daily for days 6-7, plus during the laboratory session (day 8).		varenicline 2mg varenicline: 2mg/day, with 1-week lead-in medication period. The starting dose is 0.5mg/day for days 1-2, followed by 0.5mg twice daily for days 3-5, followed by 1.0 mg twice daily for days 6-7, plus during the laboratory session (day 8).		placebo control placebo: placebo
All Cause Mortality
	Naltrexone + Varenicline		Varenicline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/9 (0%)		0/10 (0%)
Serious Adverse Events
	Naltrexone + Varenicline		Varenicline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/9 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	Naltrexone + Varenicline		Varenicline		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/11 (27.3%)		5/9 (55.6%)		4/10 (40%)
Cardiac disorders
Fast heartbeat	0/11 (0%)		1/9 (11.1%)		0/10 (0%)
Gastrointestinal disorders
Nausea/vomiting	2/11 (18.2%)		2/9 (22.2%)		1/10 (10%)
Constipation	1/11 (9.1%)		1/9 (11.1%)		0/10 (0%)
Flatulence	1/11 (9.1%)		1/9 (11.1%)		1/10 (10%)
Diarrhea	1/11 (9.1%)		4/9 (44.4%)		0/10 (0%)
General disorders
Headache	0/11 (0%)		1/9 (11.1%)		4/10 (40%)
Abnormal dreams	1/11 (9.1%)		0/9 (0%)		1/10 (10%)
Abdominal pain	2/11 (18.2%)		3/9 (33.3%)		1/10 (10%)
Erratic Behavior	0/11 (0%)		0/9 (0%)		0/10 (0%)
Dry mouth	0/11 (0%)		2/9 (22.2%)		1/10 (10%)
Insomnia	1/11 (9.1%)		1/9 (11.1%)		0/10 (0%)
Difficulty Breathing	0/11 (0%)		1/9 (11.1%)		1/10 (10%)
Tight chest	1/11 (9.1%)		1/9 (11.1%)		1/10 (10%)
Suicidal Thoughts	0/11 (0%)		0/9 (0%)		0/10 (0%)
Depressed Mood	0/11 (0%)		1/9 (11.1%)		0/10 (0%)
Appetite change	2/11 (18.2%)		0/9 (0%)		2/10 (20%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.