Neurobiology of Nicotine and Non-nicotine Components of Tobacco Addiction (NNN)

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT01056926
First received: January 14, 2010
Last updated: July 26, 2013
Last verified: July 2013
  Purpose

In the present study the investigators will measure the effects of nicotine and non-nicotine factors on brain function during cognitive processes that are differentially sensitive to these factors. One process—continuous working memory (CWM)—is implemented via a network of frontal and parietal brain regions and is highly dopamine dependent. Smoking cessation results in significant deficits in CWM which can persist for weeks and are reversed by resumption of nicotine administration in the form of smoking or nicotine replacement. Additionally, CWM deficits are observed during smoking of denic cigarettes. Brain function during CWM is modulated by smoking abstinence and subsequent nicotine administration and activity in the dlPFC is implicated in these effects. Collectively, these data suggest that CWM is highly sensitive to the nicotine, but not non-nicotine components of smoking. Brain function during CWM is altered by smoking abstinence and nicotine, but the effect of smoking, in the absence of nicotine, has not been evaluated.

Another process—cue-reactivity (CR)—results from the repeated pairing of otherwise neutral stimuli with nicotine administration. Acute smoking cessation has not been shown to have strong effects on CR in the form of cue-provoked craving, nor has nicotine replacement been shown to have robust effects on CR. Likewise, the direct effects of smoking abstinence on brain CR have been small; though craving has been shown to modulate relations between abstinence and CR. Moreover, recent data from our lab suggest larger 'doses' of abstinence (~ 24 hrs) may amplify brain responses to cues. The effect of smoking in the absence of nicotine, on CR has not, to our knowledge, been evaluated. Collectively, these data suggest that CR in the form of cue-induced craving is not highly sensitive to the effects of short-term smoking abstinence or nicotine. Brain CR is modulated by abstinence-induced craving and longer-term abstinence, but it is unclear whether abstinence from nicotine or non-nicotine components is responsible for these effects.

In the present study, we propose to evaluate the effects of non-nicotine and nicotine factors on CWM and CR using functional magnetic resonance imaging. This method allows for the non-invasive assessment of brain function. We will also examine the role of genes in moderating and mediating the effects of nicotine and non-nicotine factors on cognitive function


Condition Intervention Phase
Smoking
Behavioral: Quit smoking
Drug: Nicotine patch
Drug: Placebo Patch
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Health Services Research
Official Title: Neurobiology of Nicotine and Non-nicotine Components of Tobacco Addiction

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Measure cue reactivity while subjects undergo a functional magnetic resonance imaging (fMRI). [ Time Frame: 1.25 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Measure continuous working memory while subjects are scanned in a functional magnetic resonance imaging (fMRI). [ Time Frame: 1.25 hours ] [ Designated as safety issue: No ]

Enrollment: 147
Study Start Date: March 2009
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Nicotine Patch + Denic Smoking
Subjects will wear a nicotine patch and smoke denic cigarettes for 24 hours prior to scan
Drug: Nicotine patch
Subjects will wear a 21mg patch for 2 fMRIs, each condition lasting 2 days. They will take the patch off at night.
Experimental: Placebo Patch + Denic Smoking
Subjects will wear a placebo patch and smoke denic cigarettes 24 hours prior to scan
Drug: Placebo Patch
Subjects will wear a placebo patch for 2 fMRIs, each condition lasting 2 days. They will take the patch off at night.
Experimental: Nicotine Patch + No Smoking
Subjects will wear a nicotine patch and not smoke for 24 hours prior to scan
Behavioral: Quit smoking
Subjects will quit smoking for 2 fMRIs, each abstinence lasting 2 days
Drug: Nicotine patch
Subjects will wear a 21mg patch for 2 fMRIs, each condition lasting 2 days. They will take the patch off at night.
Experimental: Placebo Patch + No Smoking
Subjects will wear a placebo patch and not smoke for 24 hours prior to scan
Behavioral: Quit smoking
Subjects will quit smoking for 2 fMRIs, each abstinence lasting 2 days
Drug: Placebo Patch
Subjects will wear a placebo patch for 2 fMRIs, each condition lasting 2 days. They will take the patch off at night.

Detailed Description:

Overview. In a fully factorial design, thirty-six (n=36) adult smokers will undergo fMRI scanning at least 24 hours after each of the following conditions: 1) Nicotine Patch + Denic Smoking, 2) Placebo Patch + Denic Smoking, 3) Nicotine Patch + No Smoking, and 4) Placebo Patch+ No Smoking. During scanning, participants will complete a laboratory based measure of continuous working memory (n-back)—a measure of continuous working memory—and the cue-reactivity task (CR)—a measure of responses to smoking cues. Broadly, we hypothesize 1) abstinence from nicotine, regardless of smoking, will disrupt CWM performance and brain function, 2) abstinence from nicotine and denics will potentiate brain CR but differentially contribute to this effect and 3) that individual differences in smoking behavior and motivation will predict the effects of nicotine and non-nicotine factors on brain function.

  Eligibility

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

Inclusion Criteria:

  1. generally healthy,
  2. between the ages of 18 and 55,
  3. smoking of at least 10 cigarettes/day of a brand delivering > 0.5 mg nicotine according to the standard Federal Trade Commission (FTC) method,
  4. an afternoon expired carbon monoxide concentration of at least 10 ppm (to confirm inhalation),
  5. no interest in quitting smoking as measured by self-report, and
  6. right-handed as measured by a three-item scale used in our laboratory.

Exclusion Criteria:

  1. inability to attend all required experimental sessions,
  2. significant health problems (e.g., chronic hypertension, emphysema, seizure disorder, history of significant heart problems),
  3. use of psychoactive medications,
  4. use of smokeless tobacco,
  5. current alcohol or drug abuse,
  6. use of illegal drugs as measured by urine drug screen,
  7. current use of nicotine replacement therapy or other smoking cessation treatment,
  8. presence of conditions that would make MRI unsafe (e.g., pacemaker),
  9. presence of conditions contraindicated for nicotine replacement therapy (e.g., skin allergies or disorders).
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01056926

Locations
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27705
Sponsors and Collaborators
Duke University
Investigators
Principal Investigator: Joseph McClernon, Ph.D Duke University
  More Information

No publications provided

Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT01056926     History of Changes
Other Study ID Numbers: Pro00004092
Study First Received: January 14, 2010
Last Updated: July 26, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Duke University:
smoking
nicotine
Effects of nicotine and non-nicotine factors on continuous working memory.
Effects of nicotine and non-nicotine factors on cue reactivity.
Use of nicotine patches, placebo patches, and denicotinized cigarettes.
memory

Additional relevant MeSH terms:
Smoking
Habits
Nicotine
Nicotine polacrilex
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
Central Nervous System Stimulants
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 20, 2014