Nicotine Withdrawal Symptoms and Smoking Relapse

This study is currently recruiting participants.
Verified October 2013 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT01511614
First received: January 13, 2012
Last updated: March 14, 2014
Last verified: October 2013
  Purpose

Background:

- Smoking is thought to cause changes in the brain that lead to addiction and craving. Smokers who try to quit experience nicotine withdrawal symptoms that include irritability, anxiety, and difficulty concentrating. These symptoms make it difficult for people to stop smoking. Many people say that they continue smoking to help relieve these symptoms, often within the first week after trying to quit. Researchers want to study what is happening in the brain to cause these symptoms, which may help identify new ways to successfully quit smoking.

Objectives:

- To study nicotine withdrawal symptoms and brain function in smokers who stop smoking for 36 hours.

Eligibility:

- Individuals between 18 and 55 years of age who smoke at least 10 cigarettes per day. Participants must be able to stop smoking for 36 hours on two occasions.

Design:

  • This study will involve three visits to the National Institute on Drug Abuse.
  • Participants will be screened with a medical history and physical exam. Blood and urine samples will be collected, as well as breath samples to test for recent alcohol use. Participants will also fill out questionnaires and learn about the tests at the next two visits.
  • Before each imaging visit, participants will stop smoking for 36 hours. Before one visit, participants will wear a nicotine skin patch. Before the other visit, participants will wear a placebo (dummy) patch with no nicotine. Participants will not be told which type of patch they are wearing. Participants will measure the level of carbon monoxide in their breath during both of these nonsmoking periods. They will also complete questionnaires about mood and cigarette cravings.
  • Participants will have two study visits with imaging studies to measure brain activity. Each imaging visit will last about 9 to 10 hours. The visit will involve two separate 1.5- to 2-hour scan sessions (a morning scan and an afternoon scan). These scan sessions will involve tests of concentration, memory, and reaction time. Other tests and questionnaires will also be completed outside of the scanner before and after the sessions.

Condition
Nicotine Dependence

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Identifying Neurobiological Mechanisms That Underlie Acute Nicotine Withdrawal and Drive Early Relapse in Smokers

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Change in BOLD signal and FC related to task parameters, Behavioral performance, and Self-reported craving, withdrawal symptoms and mood/affect.

Secondary Outcome Measures:
  • MRS for glutamate concentration, Plasma ACTH and cortisol, Resting state CBF, ERP and EEG measures, craving and physiological responses to physical drug cues, self-report characterization measures, & amp; structural MRI and DTI data.

Estimated Enrollment: 120
Study Start Date: December 2011
Detailed Description:

Objective:

The primary objective of the current protocol is to gain a greater understanding of the neurobiological mechanisms underlying acute nicotine withdrawal and contributing to the maintenance of, or return to smoking behavior among nicotine-dependent individuals. The protocol will focus on the anhedonia, negative affect, inhibitory control deficits and impulsive decision making which accompany acute nicotine withdrawal in humans. The extent to which these acute withdrawal- related processes predict the success of smoking cessation treatment will be assessed. A secondary objective is to understand the neurobiological basis of responsivity to nicotine replacement with respect to acute nicotine withdrawal symptoms.

Study Population:

We aim to recruit 85 nicotine-dependent individuals aged 18 to 55 years who are currently seeking treatment for smoking cessation. Nicotine dependency will based on a history of 2 or more years smoking 10 plus cigarettes per day.

Design:

The study will be a within-subjects double blind placebo controlled design. All participants will complete two scanning sessions, each preceded by a 36 hour smoking abstinence period. During one abstinence period and scanning session participants will wear a dose-matched nicotine patch (non-deprived), and during the other abstinence period and scanning session, a placebo-patch (nicotine-deprived). Following participation in both scan sessions participants will commence 12 weeks of treatment involving daily varenicline administration with weekly counseling. Follow- up assessments will be conducted at 1, 6, and 12 months after their last treatment visit.

Outcome Measures:

Primary outcome measures:

  1. Change in BOLD signal and FC related to task parameters, between drug condition.
  2. Behavioral performance on each of the tasks assessing inhibitory control processes, reward responsiveness, amygdala, striatal, BNST reactivity and impulsive decision making (e.g., reaction time, error rate, hit rate, reward bias).
  3. Self-reported craving, withdrawal symptoms and mood/affect.
  4. Smoking abstinence as determined by self - reported tobacco use, urine cotinine, and breath CO.

Secondary outcome measures:

  1. MRS for glutamate concentration.
  2. Plasma ACTH and cortisol.
  3. Resting state CBF from ASL.
  4. ERP and EEG measures.
  5. Ratings and scores on self-report characterization measures.
  6. Structural MRI and DTI data.
  7. Resting state FC at 1, 6, and 12 months post- treatment.
  Eligibility

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

All participants must:

  1. Be between the ages of 18-55. Be right-handed.
  2. Be in good health.
  3. Be free of active DSM-IV dependence, or dependence in partial remission, on alcohol or any drug except nicotine. Past active dependence is acceptable provided it is at least five years in the past and total time of active dependence did not exceed 4 years. Those with past dependence may not have any current use (past 6 months) of the substance on which they were dependent. While recreational/intermittent use of alcohol and/or marijuana will be tolerated in all participant groups, individuals will be excluded if they meet current or recent (within 5 years) DSM-IV diagnostic criteria for dependence on any substances. A positive drug test for marijuana will not be exclusionary as long as participants have not used in the 24hrs preceding the imaging visits. In the event of a positive drug test for marijuana, self-reports of current marijuana use will be used to differentiate intermittent/infrequent from chronic/frequent users. Given a possible link between marijuana use and psychosis frequent users, defined as those using twice or more per week within the last month, will be excluded from participation.
  4. Be able to abstain from alcohol 24hrs before each of the imaging sessions and able to moderate their caffeine intake 12hrs before each session.
  5. Be smoking, in general of 10cpd for the last two years and continuously for at least the last month prior to coming into screening.
  6. Be actively seeking treatment for smoking cessation and willing to engage in 12-weeks of treatment involving daily administration of Varenicline and weekly counseling sessions, as well as follow-up assessments at 1, 6 and 12 months following treatment onset.
  7. Be able to abstain from smoking for 36hrs on two occasions during the study.
  8. Agree to also participate in NIDA-IRP protocol 10-DA-N457.

EXCLUSION CRITERIA:< TAB>

Participants will be excluded if they:

  1. are not suitable to undergo an fMRI experiment due to certain implanted devices (cardiac pacemaker or neurostimulator, some artificial joints, metal pins, surgical clips or other implanted metal parts), body morphology, or claustrophobia.
  2. have coagulopathies, history of, current superficial, or deep vein thrombosis, musculoskeletal abnormalities restricting an individual s ability to lie flat for extended periods of time.
  3. have HIV or Syphilis.
  4. regularly use any prescription (e.g., antidepressants, benzodiazepines, antipsychotics, anticonvulsants, barbiturates), over-the-counter (e.g., cold medicine) or herbal medication (e.g., Kava, Gingko biloba, St. John s wort) that may alter CNS function, cardiovascular function, or neuronal-vascular coupling.
  5. have any current neurological illnesses including, but not limited to, seizure disorders, frequent migraines or on prophylaxis, multiple sclerosis, movement disorders, history of significant head trauma, or CNS tumor.
  6. Have any current major psychiatric disorders to include, but not limited to, mood, anxiety, psychotic disorders, or substance-induced psychiatric disorders.
  7. are cognitively impaired or learning disabled.
  8. have significant cardiovascular or cerebrovascular conditions.
  9. have moderate to severe renal impairment
  10. are diabetic
  11. have any other major medical condition that in the view of the investigators would compromise the safety of an individual during participation. The following lab values will result in exclusion from the study:

    i. Hemoglobin < 10 g/dl

    ii. White Blood Cell Count < 2400/micro

    iii. Liver Function Tests > 3 times normal

    iv. Serum glucose > 200 mg/dl

    v. Urine protein > 2 plus

    vi. Serum creatinine > 2 mg/dl

    vii. Estimated creatinine clearance < 60ml/min

    a. The MAI will retain discretion to exclude based on less extreme lab results. After the screening process has been completed, the MAI will take into account all data collected in order to decide if there is an existing medical illness that would compromise participation in this research.

  12. pregnant, planning to become pregnant, or breastfeeding. Females are instructed in the consent to use effective forms of birth control during the study period. Urine pregnancy tests will be conducted at the beginning of each imaging visit.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01511614

Contacts
Contact: Elliot Stein, Ph.D. (443) 740-2650 estein@mail.nih.gov

Locations
United States, Maryland
National Institute on Drug Abuse Recruiting
Baltimore, Maryland, United States, 21224
Contact: For more information contact Mathew's Media Group Recruiting    800-535-8254    researchstudies@mail.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Elliot Stein, Ph.D. National Institute on Drug Abuse (NIDA)
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT01511614     History of Changes
Other Study ID Numbers: 999912474, 12-DA-N474
Study First Received: January 13, 2012
Last Updated: March 14, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Inhibitory Control
Nicotine Withdrawal
fMRI
Anhedonia
Negative Affect

Additional relevant MeSH terms:
Tobacco Use Disorder
Substance Withdrawal Syndrome
Substance-Related Disorders
Mental Disorders
Nicotine
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 April 15, 2014