High-Level Construal for Smoking Cessation

Recruiting at 1 trial location

Overseen By Elliot T Berkman, Ph.D.

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Oregon

Must be taking: Nicotine replacement

Disqualifiers: Metal implants, Claustrophobia, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 8 weeks

300 Participants Needed

Trial Summary

What is the purpose of this trial?

The objective of the proposed research is to conduct a longitudinal experiment on the neurocognitive pathways and individual differences in high-level construal for affect regulation and smoking cessation. The population is adult smokers aged 25-55 who have tried and failed to quit and who are experiencing poverty. The primary endpoints are (a) the similarity in neural representation of high-level construal to one of two candidate pathways, (b) the presence of meaningful individual differences in the neural representation of high-level construal, and (c) as a secondary endpoint, the effect size of the high-level construal condition on smoking as measured by cigarettes per day. Each of these endpoints corresponds to a specific null hypothesis. The null hypothesis for the first endpoint is that high-level construal is not significantly different in its neural representation from down-regulation of craving, which would suggest that high-level construal does not operate through distinct mechanisms from traditional treatments. The null hypothesis for the second endpoint is that the between-subjects variability in the neural representation of construal level does not significantly relate to relevant individual differences measures (e.g., traits, task behavior), which would suggest that individual differences are not meaningfully related to outcomes. Finally, the null hypothesis for the secondary endpoint is that the magnitude of the effect of high-level construal on smoking as measured by reductions in average cigarettes per day is not significantly greater than in the other conditions, which would suggest that the efficacy of the high-level construal condition is not significantly greater than a standard text-messaging intervention. The primary endpoints will be assessed at baseline and change from pre-to-post training (8 weeks).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you are required to use nicotine replacement therapy (NRT) like patches or gum during the study.

What data supports the effectiveness of the drug for smoking cessation?

Research shows that varenicline, a key component of the treatment, significantly increases the chances of quitting smoking compared to a placebo. It helps reduce cravings and withdrawal symptoms, making it easier for people to stop smoking. ^{1 2 3 4 5}

Is varenicline safe for humans?

Varenicline, also known as Chantix, is generally considered safe for humans and is approved by the FDA as a smoking cessation aid. It has been studied in various clinical trials and is known to reduce cravings and withdrawal symptoms associated with smoking. ^{1 5 6 7 8}

How does the drug varenicline differ from other smoking cessation treatments?

Varenicline is unique because it acts as a partial agonist at specific nicotine receptors, reducing cravings and withdrawal symptoms while also decreasing the rewarding effects of smoking. This dual action makes it more effective than some other treatments, like nicotine patches or bupropion, in helping people quit smoking. ^{1 2 4 6 9}

Research Team

Elliot T Berkman, Ph.D.

Principal Investigator

University of Oregon

Eligibility Criteria

Adult smokers aged 25-55, living with low income (below 200% of the federal poverty line), who have tried and failed to quit smoking. They must be willing to use nicotine replacement therapy provided or their own throughout the study. Pregnant women, individuals with metal implants, electronic medical devices, or those weighing over 550 lbs are excluded.

Inclusion Criteria

Income-to-needs ratio (INR) is less than 2.0, meaning that their household income adjusted for household size is below 200% of the federal poverty line

You smoke cigarettes regularly, at least 10 cigarettes per day for at least 1 year.

Low-SES

Exclusion Criteria

People in this population are likely to have some comorbid psychiatric, substance use, and/or other health disorders that might pose a challenge to retention and intervention compliance. Such comorbidities are inherent to the population of interest (persistent smokers) so they will not be exclusionary criteria; instead, we will gather information about psychiatric, substance use, and medical comorbidities on intake so that we can monitor and report any associations with attrition, compliance, and effects of the experimental conditions

Weight ˃ 550 lbs.

I am pregnant or might be pregnant.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

Baseline Assessment

Participants complete a multimodal battery assessing neural, behavioral, and self-report indices before randomization

1 week

1 visit (in-person)

Treatment

Participants receive text messages and complete biweekly online booster sessions for affect regulation and smoking cessation

8 weeks

Biweekly online sessions

Follow-up

Participants are monitored for changes in smoking behavior and neural activity post-treatment

4 weeks

Treatment Details

Interventions

• Down-regulation of craving for cigarettes
• High-level construal
• Treatment-as-usual control
• Up-regulation of goal energization

Trial Overview The trial is testing whether changing how people think about their goals (high-level construal) can help them regulate emotions and quit smoking more effectively than traditional methods like reducing cravings directly. Participants' brain activity will be monitored to see if this new approach works differently from standard treatments.

Participant Groups

Group I: Up-regulation of goal energization Experimental Treatment 1 Intervention

Participants will be sent messages that encourage them to consider the core values that drive their desire to quit smoking.

Group II: High-level construal Experimental Treatment 1 Intervention

Participants will be sent messages asking them to imagine what their lives will look like in the future if they succeed ("What would quitting mean to you and your family's future?"; Yeager et al., 2014).

Group III: Effortful down-regulation of craving for cigarettes Experimental Treatment 1 Intervention

Participants will be sent messages that encourage inhibitory control of cravings for cigarettes (e.g., using cognitive reappraisal or attentional control) and that provide strategies to do so (e.g., "When you feel an urge to smoke, think about the health consequences").

Down-regulation of craving for cigarettes is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Chantix for:

• Smoking cessation
• Dry eye disease (for Tyrvaya nasal spray)

Approved in Canada as Champix for:

• Smoking cessation

Approved in European Union as Champix for:

• Smoking cessation

Who Is Running the Clinical Trial?

University of Oregon

Lead Sponsor

Trials

91

Recruited

46,700+

Ohio State University

Collaborator

Trials

891

Recruited

2,659,000+

Findings from Research

Varenicline, a recently approved smoking cessation drug, has been shown to significantly increase abstinence rates compared to placebo and other treatments like bupropion SR and nicotine patches, with rates tripling compared to placebo.

In addition to improving abstinence, varenicline effectively reduces cravings and withdrawal symptoms, supporting its mechanism as a partial agonist that diminishes the rewarding effects of smoking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Varenicline in the treatment of tobacco dependence. Fagerström, K., Hughes, J.[2021]

Varenicline is the most effective medication for smoking cessation, achieving cessation rates of 25-35% after one year, despite high recidivism rates among smokers.

The study found that varenicline reduces anticipatory reward processing in smokers, which may help decrease the desire to smoke by altering brain circuits related to reward, thus contributing to its effectiveness as a treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reward Anticipation Is Differentially Modulated by Varenicline and Nicotine in Smokers. Fedota, JR., Sutherland, MT., Salmeron, BJ., et al.[2019]

In a study of 17 non-treatment seeking adult smokers, extended pre-treatment with varenicline for 21 days significantly reduced the number of cigarettes smoked per day and smoking urges, particularly during the later days of treatment.

The findings suggest that a longer duration of varenicline pre-treatment may enhance its effectiveness in promoting smoking cessation, as reductions in smoking behavior and cravings were observed only after the typical one-week adjustment period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of 21 days of varenicline versus placebo on smoking behaviors and urges among non-treatment seeking smokers. Ashare, RL., Tang, KZ., Mesaros, AC., et al.[2021]

Varenicline, a medication for smoking cessation, works by targeting both the reinforcing effects of nicotine and its ability to enhance the appeal of environmental cues, which can influence smoking behavior.

The effectiveness of Varenicline may vary among smokers, particularly benefiting those who are more sensitive to nicotine's effects on their environment, suggesting a personalized approach to treatment could be advantageous.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Varenicline Targets the Reinforcing-Enhancing Effect of Nicotine on Its Associated Salient Cue During Nicotine Self-administration in the Rat. Garcia-Rivas, V., Fiancette, JF., Cannella, N., et al.[2020]

In a study involving 47 treatment-seeking heavy drinkers, varenicline did not reduce alcohol cue-induced craving compared to a placebo, indicating it may not be effective in blunting cravings in this context.

However, the study found that higher levels of craving measured during the cue reactivity tests were predictive of increased alcohol use in real-world settings, highlighting the importance of craving as a potential indicator of drinking behavior.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Alcohol Cue Reactivity on Subsequent Treatment Outcomes Among Treatment-Seeking Individuals with Alcohol Use Disorder: A Multisite Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Varenicline. Miranda, R., O'Malley, SS., Treloar Padovano, H., et al.[2021]

Varenicline, an FDA-approved smoking cessation aid, has been shown to effectively signal reward-seeking behavior in rats, indicating its potential to help with smoking cessation by mimicking nicotine's effects at specific brain receptors.

The study demonstrated that the effects of varenicline are primarily mediated through its partial agonist activity at alpha4beta2 nicotinic acetylcholine receptors, suggesting that targeting these receptors could enhance the development of new smoking cessation therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Varenicline serves as the training stimulus in the drug-discriminated goal-tracking task with rats: initial evaluation of potential neuropharmacological processes. Thompson, BM., Tracy, ME., Huynh, YW., et al.[2023]

Varenicline effectively inhibits nicotine-enhanced brain stimulation reward (BSR), supporting its role as a smoking cessation aid, as shown through experiments with varying doses of nicotine and varenicline.

The mechanism of action for varenicline's effects is primarily through the activation of alpha4beta2 nicotinic receptors, while alpha7 receptors do not appear to play a significant role in this process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Varenicline attenuates nicotine-enhanced brain-stimulation reward by activation of alpha4beta2 nicotinic receptors in rats. Spiller, K., Xi, ZX., Li, X., et al.[2021]

In a study involving 8 cigarette smokers, acute administration of varenicline (0.5, 1, and 2 mg) did not significantly alter smoking or eating behavior, suggesting it may not have immediate behavioral effects.

In contrast, methylphenidate, used as a positive control, increased smoking behavior and decreased caloric intake, highlighting the need for further research on the long-term effects of varenicline on smoking and eating behaviors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The influence of acute varenicline administration on smoking and eating behavior in humans. Stoops, WW., Vansickel, AR., Glaser, PE., et al.[2015]

Varenicline, a medication for smoking cessation, not only reduces withdrawal symptoms and nicotine reinforcement but also blunts brain responses to smoking cues, which helps decrease cravings.

In a study involving nicotine-dependent smokers, varenicline significantly reduced activity in brain regions associated with craving when exposed to smoking cues, indicating a new mechanism that likely enhances its effectiveness in helping people quit smoking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of varenicline on smoking cue–triggered neural and craving responses. Franklin, T., Wang, Z., Suh, JJ., et al.[2022]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Varenicline in the treatment of tobacco dependence. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Reward Anticipation Is Differentially Modulated by Varenicline and Nicotine in Smokers. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Effects of 21 days of varenicline versus placebo on smoking behaviors and urges among non-treatment seeking smokers. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Varenicline Targets the Reinforcing-Enhancing Effect of Nicotine on Its Associated Salient Cue During Nicotine Self-administration in the Rat. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Effects of Alcohol Cue Reactivity on Subsequent Treatment Outcomes Among Treatment-Seeking Individuals with Alcohol Use Disorder: A Multisite Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Varenicline. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Varenicline serves as the training stimulus in the drug-discriminated goal-tracking task with rats: initial evaluation of potential neuropharmacological processes. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Varenicline attenuates nicotine-enhanced brain-stimulation reward by activation of alpha4beta2 nicotinic receptors in rats. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

The influence of acute varenicline administration on smoking and eating behavior in humans. [2015]

9. United States pubmed.ncbi.nlm.nih.gov

Effects of varenicline on smoking cue–triggered neural and craving responses. [2022]