Neural Mechanisms Associated With Risk of Smoking Relapse

Nicotine Addiction Clinical Trial

Official title:

Neural Mechanisms Associated With Risk of Smoking Relapse

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02837510
• Other study ID #: 824061
• Status: Active, not recruiting
• Phase: N/A
• Start date: May 2016
• Est. completion date: October 31, 2024

Study information

• Verified date: December 2023
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 250
• Est. completion date: October 31, 2024
• Est. primary completion date: June 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Nicotine Addiction
• Tobacco Use Disorder

Intervention

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.

Locations

Country	Name	City	State
United States	University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
University of Pennsylvania

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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

External Links

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