Nicotine Withdrawal Symptoms and Smoking Relapse

Nicotine Dependence Clinical Trial

Official title: Identifying Neurobiological Mechanisms That Underlie Acute Nicotine Withdrawal and Drive Early Relapse in Smokers

Status Completed

Clinical Trial Summary

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 65 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:

Phase 1

• This study will involve three visits to the National Institute on Drug Abuse.

• NOT be able to smoke for 36 hours before the two imaging visits.

• Wear a nicotine skin patch or a placebo (fake) patch during your 36 hour smoking abstinence period and study visits.

• Have your blood drawn to test for levels of stress-related hormones.

• Complete multiple MRI scanning sessions that last about 1.5 to 2 hours each.

• Undergo EEG (brain waves) recording.

• Answer questionnaires about how you think and feel.

• Complete various tasks and procedures inside and outside of the MRI scanner.

Phase 2

• This study will involve thirteen visits to the National Institute on Drug Abuse.

• Set a quit date and develop a treatment plan with a study therapist.

• Take Chantix (varenicline) every day for a period of 12 weeks.

• Meet for weekly and biweekly counseling sessions with a therapist.

• Answer questionnaires about how you think and feel.

Phase 3

• This study will involve three visits to the National Institute on Drug Abuse.

• Complete an MRI scanning session that will last about 20min each visit

• Meet with a study staff member on each visit who will ask you questions about your smoking behavior and how you think and feel.

Clinical Trial 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, in the service of developing future smoking cessation treatments. The Nicotine Withdrawal Syndrome is a major cause of failed quit attempts in smokers, and targeting this time period for intervention may help improve smoking cessation outcomes.

Study Population

We will recruit treatment seeking and non-treatment seeking smokers, as well as matched non-smoker control participants.

Design

There are 3 arms included in this protocol, each of which aims to understand the neurobiology of the Nicotine Withdrawal Syndrome during the initial quit period, with the broader goal of increasing quit success rate in the future.

Main Study: To understand (1) the acute neurobiological effects of nicotine withdrawal on treatment-seeking and non-treatment seeking smokers, (2) the long term neurobiological outcomes of varenicline treatment and smoking cessation counseling at 1, 6, and 12 months. We will recruit 85 treatment seeking and 35 non-treatment seeking smokers for a within (nicotine deprivation), between (treatment-seeking status) subjects randomized, double blind, placebo controlled study.

Motivational Interviewing Arm: (1) To increase motivation and preparation for smoking cessation treatment among individuals who express an interest in quitting smoking but are not currently ready to enter treatment, in the service of increasing quit success rate and (2) to understand the neurobiological basis of motivation to quit smoking, and the interaction between motivation to quit and mechanisms that underlie acute nicotine withdrawal. We will recruit 300 current smokers interested in quitting smoking, but not yet ready to set a quit date.

Transcranial Direct Current Stimulation (tDCS) Arm: To understand the acute effect of tDCS on 3 large-scale brain networks dysregulated in nicotine addiction and withdrawal, the Default Mode Network, the Executive Control Network, and the Salience Network. We will enroll 60 non-treatment seeking smokers, with the expectation of 35 completers; and enroll 55 non-smoking controls, with the expectation of 45 completers, for a double blind, sham controlled, randomized crossover study. Smokers will be studied in nicotine abstinence and nicotine sated conditions, as in the Main Study design.

Outcome measures

Primary outcome measures:

1. Change in BOLD signal and FC related to task parameters, between drug (or tDCS) condition.

2. Behavioral performance on each of the tasks assessing inhibitory control processes, reward responsiveness, amygdala, striatal, BNST reactivity, impulsive decision making, cue reactivity and working memory (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. ;

Related Conditions & MeSH terms

• Nicotine Dependence
• Tobacco Use Disorder

• NCT number: NCT01511614
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Completed
• Phase: N/A
• Start date: May 20, 2013
• Completion date: March 30, 2020