Varenicline and Nicotine Interactions in Humans (VA)

Varenicline Attenuates Some of the Subjective and Physiological Effects of Intravenous Nicotine in Humans.

To examine the effects of varenicline on the subjective, physiological and cognitive responses to intravenous nicotine. Varenicline is a partial nicotine agonist and it is approved as a treatment for smoking cessation. We predict that varenicline treatment will modify subjective, physiological and cognitive responses to IV nicotine.

Study Overview

• Status: Completed
• Conditions: Smoking Cessation
• Intervention / Treatment: Drug: Placebo; Drug: Varenicline; Drug: IV Nic

Detailed Description

This will be a 2-4 week double-blind, placebo-controlled study. Twenty four male and female smokers will have two 4-day treatment periods, in which they will be randomized to varenicline (1 mg/day) or placebo. During the first 3 days of each treatment period, smokers will have daily clinic visits and receive their study medication. On Day 4, subjects will come to the laboratory, where they will receive ascending doses of intravenous (IV) nicotine (0.1, 0.4, and 0.7 mg per 70kg). This procedure will allow accurate assessment of varenicline effects on the subjective, physiological and cognitive responses to nicotine. Following a washout period, subjects will be crossed over to the alternative treatment.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • West Haven, Connecticut, United States, 06516
      • Veterans Affairs Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Female and male smokers, aged 18 to 55 years
• History of smoking daily for the past 12 months, at least 15 cigarettes daily
• Carbon Monoxide (Alveolar) level > 10ppm
• For women: not pregnant as determined by pregnancy screening, nor breast feeding, and using acceptable birth control methods

Exclusion Criteria:

• History of heart disease, renal or hepatic diseases
• other medical conditions that the physician investigator deems as contraindicated for the subject to be in the study
• Regular use of psychotropic medication (antidepressants, antipsychotics, or anxiolytics)
• recent psychiatric diagnosis and treatment for Axis I disorders including
• major depression, bipolar affective disorder,
• schizophrenia and panic disorder within the past year
• Current dependence on alcohol
• drugs or treatments for drug
• alcohol addiction within the past 5 years
• Allergy to varenicline

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Placebo First, varenicline, + IV Nic; Subjects received a Placebo tablet once per day for 4 days and then received a laboratory session where they were given ascending doses of Nicotine (0.1, 0.4, and 0.7 mg per 70 kg).After a minimum of a 5 day washout subjects then received varenicline tablet (1mg). once per day for 4 days and then received a laboratory session where they were given ascending doses of Nicotine (0.1,0.4,0.7 mg per 70kg).	Drug: Placebo; Sugar Pill; Other Names: Sugar Pill; Drug: Varenicline; Varenicline (1 mg per day) given for 4 days prior to laboratory session; Other Names: Chantix; Drug: IV Nic; IV Nicotine given during the laboratory session following 4 days of exposure to the study medication (varenicline or placebo). This nicotine was given during each laboratory session which followed the 4 days of exposure to either placebo then varenicline or varenicline then placebo.; Other Names: IV Nicotine
Experimental: Varenicline first, placebo, + IV Nic; Subjects received Varenicline tablet (1 mg) per day for 4 days and then received a laboratory session where they were given ascending doses of Nicotine (0.1, 0.4, and 0.7 mg per 70 kg). After a washout of a minimum of 5 days subjects then received placebo tablet for per day for 4 days and then received a laboratory session where they were given ascending doses of Nicotine (0.1,0.4,, and 0.7mg per 70 kg).	Drug: Placebo; Sugar Pill; Other Names: Sugar Pill; Drug: Varenicline; Varenicline (1 mg per day) given for 4 days prior to laboratory session; Other Names: Chantix; Drug: IV Nic; IV Nicotine given during the laboratory session following 4 days of exposure to the study medication (varenicline or placebo). This nicotine was given during each laboratory session which followed the 4 days of exposure to either placebo then varenicline or varenicline then placebo.; Other Names: IV Nicotine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjective Responses to Intravenous Nicotine	The Drug Effects Questionaire( DEQ) is a 7-item psychometric that measures the following subjective categories: 'drug strength',' high', 'feels stimulated', 'good effects', 'bad effects', 'head rush', and 'like the drug'. Smokers rated each item on a 100 millimeter scale from "not at all" (a score of 0) to "extremely" with a maximum score of 100.	30 minutes after each nicotine infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Reaction Time (RT) on Modified Stroop Task.	A Modified stroop task was used to assess attentional responses to smoking and negative affect cues. Cues were presented as blue, red or green text. Subjects completed 2 counterbalanced blocks (60 trials per block). One block contained smoking cues and neutral cues. The other block contained negative affect cues and a different set of matched neutral cues. The 2 blocks were administered twice during each experimental session - prior to nicotine infusion, and 30 mins after the last nicotine infusion (2 hrs and 45 mins after medication dosing). The Stroop effect is a differential RT when identifying the colors of words presented as neutral cues vs. emotional cues (i.e. smoking or negative affect cues).	pre-nicotine, and 30 min after last nicotine infusion (Post-Nicotine)
Cotinine Levels	Subject Cotinine Levels before each laboratory session.	Before each laboratory session on day 5
Heart Rate	The average peak change (change score = maximum post dose score minus predose baseline) in heart rate was calculated.	30 minutes after each nicotine infusion
Changes in Systolic and Diastolic Blood Pressure	The average peak change (change score = maximum post dose score minus predose baseline) in systolic and diastolic blood pressure after nicotine infusion.	30 minutes after each nicotine infusion

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute on Drug Abuse (NIDA); US Department of Veterans Affairs
• Investigators: Principal Investigator: Mehmet Sofuoglu, M.D., Ph.D., Yale University Associate Professor

Publications and helpful links

General Publications

• Sofuoglu M, Herman AI, Mooney M, Waters AJ. Varenicline attenuates some of the subjective and physiological effects of intravenous nicotine in humans. Psychopharmacology (Berl). 2009 Nov;207(1):153-62. doi: 10.1007/s00213-009-1643-z. Epub 2009 Aug 20.

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (Actual): November 1, 2008
• Study Completion (Actual): November 1, 2009

Study Registration Dates

• First Submitted: January 23, 2008
• First Submitted That Met QC Criteria: February 4, 2008
• First Posted (Estimate): February 5, 2008

Study Record Updates

• Last Update Posted (Estimate): September 25, 2014
• Last Update Submitted That Met QC Criteria: September 9, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Keywords: therapeutic effects
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Nicotine; Varenicline
• Other Study ID Numbers: HIC # 0702002338; DPMC (Other Identifier: NIDA); R01DA014537 (U.S. NIH Grant/Contract); MIRECC 000000000 (Registry Identifier: Department of Veteran's Affairs)