Neural Mechanisms Associated With Risk of Smoking Relapse

This study will examine how abstinence-induced brain changes contribute to smoking cessation outcomes in treatment-seeking smokers.

Study Overview

• Status: Active, not recruiting
• Conditions: Nicotine Addiction
• Intervention / Treatment: Behavioral: Standard smoking cessation counseling

Detailed Description

Smoking is the greatest preventable cause of mortality and a significant economic burden. Even with the best available treatments, most smokers relapse within days or weeks after a quit attempt. Nicotine replacement therapy, the most widely used pharmacotherapy, yields end of treatment quit rates of <25% suggesting that managing nicotine withdrawal is not sufficient. To improve quit rates significantly, a more refined mechanistic understanding is needed. Neuroimaging can identify mechanisms underlying behavior change beyond self-report and behavioral measures. Functional magnetic resonance imaging (fMRI) studies show that brief (e.g., 24 hr.) abstinence from smoking produces working memory deficits associated with reduced neural activity in cognitive control circuits and weakened resting state functional connectivity. Neural reactivity to smoking cues also increases risk of relapse, and psychological stress can enhance neural responses to smoking cues and increase smoking intensity. This study will examine how abstinence-induced brain changes contribute to clinical outcomes in treatment-seeking smokers. Using a validated fMRI abstinence challenge paradigm, 200 treatment-seeking smokers will complete two 1-hour pre-treatment fMRI scans: after smoking satiety and after 24 hours of confirmed abstinence. The investigators will examine brain responses during performance of tasks probing working memory, cue reactivity, and stress response as well as resting state functional connectivity. Participants will then set a target quit date, receive smoking cessation counseling, and be monitored for 6 months to assess time to relapse using a validated smoking relapse protocol.

• Study Type: Interventional
• Enrollment (Estimated): 250
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Eligible participants will be:

1. Treatment-seeking smokers between the ages of 18 and 65, reporting consumption of at least 5 cigarettes per day for at least the past 6 months;
2. Planning to live in the area for at least the next 3 months;
3. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the combined consent and HIPAA form;
4. Able to communicate fluently in English (speaking, writing, and reading).

Exclusion Criteria:

Subjects who present and/or self-report with the following criteria at any point during study participation will not be eligible to participate in the study:

Smoking Behavior:

1. Use of chewing tobacco or snuff or cigars;
2. Current enrollment or plans to enroll in another smoking cessation program or research study in the next 3 months;
3. Current or anticipated (within the next 3 months) use of smoking cessation medications or nicotine replacement therapy (NRT);
4. A baseline carbon monoxide (CO) reading less than or equal to 8ppm.

Alcohol/Drugs:

1. Diagnosis or treatment for alcohol or drug abuse in the past two years as reported during phone screen (e.g., alcohol, opioids, cocaine, or stimulants);
2. Current alcohol consumption that exceeds 25 standard drinks/week;

3. Positive breath alcohol concentration test (BrAC greater than or equal to 0.01) at intake;

   a. Participants testing positive for breath alcohol with a reading equal to or greater than .08 (the legal driving limit) or who are visibly impaired will be instructed not to drive themselves home after the appointment. If a participant needs to use a phone to call for a safe ride home, an office telephone will be made available to the participant.

4. A positive urine drug screen for cocaine, opiates, PCP, benzodiazepines, methadone, MDMA, amphetamine, methamphetamine, tri-cyclic antidepressants and/or barbiturates at any session;

Medication:

Current use or recent discontinuation (within the past 30 days at the time of Intake) of:

1. Smoking cessation medication (e.g., Zyban, Wellbutrin, Wellbutrin SR, Chantix, NRT);
2. Anti-psychotic medications;
3. Anti-depressants (tricyclics, SSRI's, selective and nonselective MAOIs, Wellbutrin/Zyban);
4. Anti-anxiety agents;
5. Anti-panic agents;
6. Prescription (e.g., Provigil, Ritalin) or over-the-counter stimulants;
7. Prescription sleep aids (e.g., Ambien, Lunesta) if used more than 2x/week. If participants report use less than twice a week, they will just be asked to refrain from use during imaging portion of the study.

8. Any medication that could compromise participant safety as determined by the Principal Investigator and/or Study Physician;

   Daily use of:

9. Opiate-containing medications for chronic pain.

Medical/Neuropsychiatric:

1. Women who are pregnant, planning a pregnancy, and/or breast feeding. All female subjects of childbearing potential will undergo a urine pregnancy test at Intake and both fMRI scan visits (3 urine pregnancy tests in total).
2. History of epilepsy or a seizure disorder;
3. History of stroke;
4. Self-reported brain or spinal tumor;
5. Self-reported history or current diagnosis of psychosis, bipolar disorder, schizophrenia, current major depression (subjects with a history of major depression but in remission for past 6 months are eligible), or any Axis 1 disorder.

fMRI-Related:

1. Self-reported history of head trauma;
2. Self-reported brain (or CNS) or spinal tumor;
3. Self-reported use of pacemakers, certain metallic implants, or presence of metal in the eye as contraindicated for fMRI;
4. Self-reported history of claustrophobia;
5. Being left-handed;
6. Color blindness;
7. Weight greater than 299lbs;
8. Self-reported history of gunshot wounds;
9. Any impairment preventing participants from using the response pad necessary for the cognitive testing;
10. Circumstances or conditions that may interfere with magnetic resonance imaging (MRI).

General Exclusion:

1. Any medical condition, illness, disorder, or concomitant medication that could compromise participant safety or treatment, as determined by the Principal Investigator;
2. Low or borderline intellectual functioning - determined by a score of less than 85 on the Shipley Institute of Living Scale (SILS) (administered at Intake Visit);
3. Enrollment or plans to enroll in another research study;
4. Inability to provide informed consent or complete any of the study tasks as determined by the Principal Investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Standard smoking cessation counseling; Participants will receive a standard treatment program consisting of smoking cessation counseling.

Behavioral: Standard smoking cessation counseling; Participants will discuss reasons for quitting, the model of smoking as a learned habit, triggers for smoking, and trigger management; receive brief training in how to manage withdrawal symptoms and relapse prevention counseling and receive the NCI Clearing the Air self-help smoking cessation booklet. The target quit date (TQD) session will be scheduled to occur up to 2 weeks following the pre-quit session. Participants will then meet with a smoking cessation counselor for a 15 minute booster counseling session. During the first week following TQD there will be two monitoring visits to closely monitor abstinence. Weekly thereafter for four weeks, participants will attend a brief booster counseling session.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Days to relapse	The primary outcome will be the number of days to relapse following the target quit date. Relapse will be confirmed using a conventional SRNT guideline criterion of either a positive biochemical verification of smoking or 7 consecutive days of smoking based on self-report (it is very unlikely that a subject would meet the latter criterion without also meeting the former, given the long half-life of cotinine). The days to relapse will be based upon time from target quit date to the first day of the relapse period. Self-reported daily smoking data will be collected using a validated timeline follow-back method. Self-reported abstinence will be biochemically verified on a weekly basis using urine cotinine (<100ng/ml) and a CO reading of ≤5PPM. Drop-outs will be considered relapsers following the last date of abstinence data provided.	6 months after target quit date

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mood	The Positive and Negative Affect Schedule (PANAS), a 20-item Likert-format self-report measure, will be used to assess Positive Affect (PA; 10 items, e.g., enthusiastic, strong) and Negative Affect (NA; 10 items, e.g., distressed, upset), two dominant and generally orthogonal dimensions of affect. This measure will be administered at all study visits	Target Quit Date through 6-month follow-up
Nicotine withdrawal	The Revised Minnesota Nicotine Withdrawal Scale (MNWS-R) is a fifteen-item self-report measure where participants rate their feelings of withdrawal on a scale of 0 (none) to 4 (severe). This measure will be administered at all study visits.	Target Quit Date through 6-month follow-up
Smoking Urges/Craving	The 10-item brief QSU-B questionnaire on smoking urges will be administered at the same time points to assess cravings to smoke. The QSU-B contains 2 subscales (anticipation of reward, relief from negative affect).	Target Quit Date through 6-month follow-up
Stress/Anxiety	Anxiety will be measured at intake and at both fMRI scanning sessions using the State-Trait Anxiety Index, which has been used as a covariate in fMRI studies of stress response.	1-2 weeks following intake session

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Investigators: Principal Investigator: James Loughead, Ph.D., University of Pennsylvania

Publications and helpful links

General Publications

• Allenby C, Falcone M, Wileyto EP, Cao W, Bernardo L, Ashare RL, Janes A, Loughead J, Lerman C. Neural cue reactivity during acute abstinence predicts short-term smoking relapse. Addict Biol. 2020 Mar;25(2):e12733. doi: 10.1111/adb.12733. Epub 2019 Feb 25.

Helpful Links

• Click here for more information about this study: Neural mechanisms associated with risk of smoking relapse

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2016
• Primary Completion (Actual): June 1, 2023
• Study Completion (Estimated): October 31, 2024

Study Registration Dates

• First Submitted: June 3, 2016
• First Submitted That Met QC Criteria: July 14, 2016
• First Posted (Estimated): July 19, 2016

Study Record Updates

• Last Update Posted (Estimated): December 12, 2023
• Last Update Submitted That Met QC Criteria: December 11, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Tobacco Use Disorder
• Other Study ID Numbers: 824061

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO