Varenicline and Nicotine Interactions in Humans (VA)

This study has been completed.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Yale University
ClinicalTrials.gov Identifier:
NCT00606892
First received: January 23, 2008
Last updated: September 9, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention
Smoking Cessation
Drug: Varenicline
Drug: Placebo
Drug: IV Nic

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Varenicline Attenuates Some of the Subjective and Physiological Effects of Intravenous Nicotine in Humans.

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • Subjective Responses to Intravenous Nicotine [ Time Frame: 30 minutes after each nicotine infusion ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Mean Reaction Time (RT) on Modified Stroop Task. [ Time Frame: pre-nicotine, and 30 min after last nicotine infusion (Post-Nicotine) ] [ Designated as safety issue: No ]
    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).

  • Cotinine Levels [ Time Frame: Before each laboratory session on day 5 ] [ Designated as safety issue: No ]
    Subject Cotinine Levels before each laboratory session.

  • Heart Rate [ Time Frame: 30 minutes after each nicotine infusion ] [ Designated as safety issue: Yes ]
    The average peak change (change score = maximum post dose score minus predose baseline) in heart rate was calculated.

  • Changes in Systolic and Diastolic Blood Pressure [ Time Frame: 30 minutes after each nicotine infusion ] [ Designated as safety issue: Yes ]
    The average peak change (change score = maximum post dose score minus predose baseline) in systolic and diastolic blood pressure after nicotine infusion.


Enrollment: 37
Study Start Date: August 2007
Study Completion Date: November 2009
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: Varenicline
Varenicline (1 mg per day) given for 4 days prior to laboratory session
Other Name: Chantix
Drug: Placebo
Sugar Pill
Other Names:
  • Placebo
  • Sugar Pill
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 Name: 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: Varenicline
Varenicline (1 mg per day) given for 4 days prior to laboratory session
Other Name: Chantix
Drug: Placebo
Sugar Pill
Other Names:
  • Placebo
  • Sugar Pill
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 Name: IV Nicotine

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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  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: NCT00606892

Locations
United States, Connecticut
Veterans Affairs Hospital
West Haven, Connecticut, United States, 06516
Sponsors and Collaborators
Yale University
Investigators
Principal Investigator: Mehmet Sofuoglu, M.D., Ph.D. Yale University Associate Professor
  More Information

Publications:
Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT00606892     History of Changes
Other Study ID Numbers: HIC # 0702002338, MIRECC 000000000, DPMC, R01DA014537
Study First Received: January 23, 2008
Results First Received: March 14, 2012
Last Updated: September 9, 2014
Health Authority: United States: Federal Government

Keywords provided by Yale University:
therapeutic effects

Additional relevant MeSH terms:
Nicotine
Varenicline
Ganglionic Stimulants
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 16, 2014