Propranolol + Nicotine Patch for Smoking Addiction

Overseen By Isabel Brush, B.A.

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Oklahoma

Must not be taking: Psychoactive drugs, Beta-blockers

Disqualifiers: Pregnancy, Cardiovascular disease, Asthma, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how combining a nicotine patch with propranolol, a beta-blocker, affects smokers' brains and behavior when they encounter smoking triggers. The goal is to understand how these treatments work together and separately to influence the desire to smoke. Participants will not need to quit smoking during the trial. The trial seeks individuals who have smoked at least five cigarettes a day for over a year and can easily identify four places where they typically smoke each week. As a Phase 4 trial, this research aims to understand how these FDA-approved treatments can benefit more patients.

Will I have to stop taking my current medications?

Yes, you will need to stop taking any psychoactive medications, smokeless tobacco, smoking cessation medications, nicotine products, beta-adrenergic medications, or other blood pressure medications to participate in this trial.

What is the safety track record for these treatments?

Research has shown that propranolol is usually safe for use. In one study involving 52 male smokers, a single dose of propranolol revealed no major safety issues. Propranolol often helps alleviate symptoms like irritability when quitting smoking.

The nicotine patch is also considered safe. Studies indicate it is generally well-tolerated for long-term use and helps ease withdrawal symptoms by providing a steady amount of nicotine without smoking.

When propranolol and the nicotine patch are used together, a study with 73 participants found no major safety concerns. This suggests that using these treatments together is likely safe for a short time. However, these treatments in the trial are not intended for long-term use or smoking cessation. Participants will only use them briefly. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for smoking addiction because they explore a novel combination approach. Unlike standard treatments like nicotine replacement therapy or medications like varenicline, this trial combines propranolol, a beta-blocker typically used for heart issues, with nicotine patches. This combination is unique because propranolol may help reduce the anxiety and stress associated with quitting smoking, potentially making it easier for individuals to stick with their quit plan. By targeting both the physical cravings and the emotional challenges of quitting, this approach could offer a more comprehensive solution for those struggling with smoking addiction.

What evidence suggests that this trial's treatments could be effective for smoking addiction?

Research has shown that nicotine patches, one of the treatments in this trial, can help people quit smoking. Smokers using the real patch are more than twice as likely to quit compared to those using a fake patch. However, the patch's effectiveness can decrease over time, with about 20% of people remaining smoke-free at six months and 9% at a year.

For propranolol, another treatment option in this trial, studies suggest it might reduce cravings and the desire to smoke by altering how the brain reacts to smoking triggers. However, it does not significantly increase the chances of quitting smoking on its own. This trial will test the combination of propranolol with nicotine patches, as well as each treatment individually, to evaluate their effectiveness in helping participants quit smoking. ^{1 5 6 7 8}

Who Is on the Research Team?

Jason A Oliver, PhD

Principal Investigator

University of Oklahoma

Are You a Good Fit for This Trial?

This trial is for English-speaking, right-handed adults aged 21-60 who have been smoking regularly for at least a year. Participants should smoke over 5 cigarettes daily and be generally healthy. Exclusions include low blood pressure, use of psychoactive drugs or certain medications, pregnancy, abnormal EKG results, severe anemia or electrolyte issues, MRI safety risks like pacemakers, vision problems uncorrectable with glasses/contacts, and significant health conditions.

Inclusion Criteria

Able to read and understand English

Must identify at least 4 different smoking locations used in a typical week

I smoke 5 or more cigarettes daily.

Exclusion Criteria

Problems with vision that cannot be corrected with contacts or glasses

Significant health problems that would preclude active participation

Presence of conditions that would make MRI unsafe (e.g. pacemaker) or (e.g. weight and body shape)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline

Participants undergo baseline assessments including consent and initial measurements

1 week

Neuroimaging Sessions

Participants attend four neuroimaging appointments, each lasting approximately 5 hours, to assess neural and behavioral responses to smoking cues

4 weeks

4 visits (in-person)

Follow-up

Participants are monitored for any delayed effects or safety concerns after the neuroimaging sessions

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Nicotine Patch
• Placebo Patch
• Placebo Propranolol
• Propranolol

Trial Overview The study tests the effects of Propranolol (a beta-blocker) and nicotine patches on smokers' reactions to cues that make them want to smoke. It's not a long-term treatment test but looks at immediate responses in controlled settings. Participants will receive either the actual drugs or placebos in various combinations.

How Is the Trial Designed?

Group I: Placebo Patch/Active Propranolol Experimental Treatment 2 Interventions

Placebo Nicotine Patch Active Propranolol (40 mg, immediate release)

Group II: Active Patch/Placebo Propranolol Experimental Treatment 2 Interventions

Active Nicotine Patch (14 mg) Placebo Propranolol

Group III: Active Patch/Active Propranolol Experimental Treatment 2 Interventions

Active Nicotine Patch (14 mg) Active Propranolol (40 mg, immediate release)

Group IV: Placebo Patch/Placebo Propranolol Placebo Group 2 Interventions

Placebo Nicotine Patch Placebo Propranolol

Who Is Running the Clinical Trial?

University of Oklahoma

Lead Sponsor

Trials

484

Recruited

95,900+

Oklahoma State University Center for Health Sciences

Collaborator

Trials

37

Recruited

4,900+

Duke University

Collaborator

Trials

2,495

Recruited

5,912,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Published Research Related to This Trial

In a double-blind clinical trial with 73 participants, propranolol showed no significant effect on helping smokers quit, as only six individuals stopped smoking after eight weeks, equally split between the propranolol and placebo groups.

The results indicate that propranolol is not an effective intervention for smoking cessation, highlighting the need for alternative strategies to support individuals trying to quit smoking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Propranolol and giving up smoking. Farebrother, MJ., Pearce, SJ., Turner, P., et al.[2013]

A study involving 52 male smokers showed that administering propranolol before reactivating nicotine-related memories significantly reduced cravings for smoking, indicating its potential as a treatment for nicotine dependence.

The research demonstrated that propranolol disrupts the reconsolidation of smoking-related memories by affecting brain regions involved in memory and reward processing, suggesting a mechanism for how it can help manage cravings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neural substrates of propranolol-induced impairments in the reconsolidation of nicotine-associated memories in smokers. Lin, X., Deng, J., Yuan, K., et al.[2023]

In a study involving 15 overnight abstinent smokers, carvedilol effectively reduced the cardiovascular effects of nicotine, such as increased heart rate and blood pressure, indicating its potential as a protective agent against nicotine's harmful cardiovascular effects.

Carvedilol also decreased the self-reported 'bad effects' of nicotine, suggesting that noradrenergic activation may play a role in the negative experiences associated with nicotine use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adrenergic blocker carvedilol attenuates the cardiovascular and aversive effects of nicotine in abstinent smokers. Sofuoglu, M., Mouratidis, M., Yoo, S., et al.[2018]

Cigarette smoking is the leading cause of preventable death in the U.S., with over 3,000 children starting to smoke daily, highlighting the urgent need for effective smoking cessation strategies.

Pharmacological interventions, such as Zyban and various nicotine replacement therapies (like patches and gum), can help alleviate withdrawal symptoms and support individuals in quitting smoking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using nicotine replacement therapy in treating nicotine addiction in adolescents. Maharaj, K., Ternullo, S.[2018]

Long-acting propranolol (Inderal LA) provides a controlled release of the medication, maintaining higher plasma concentrations over 24 hours compared to conventional tablets, which helps ensure consistent beta-adrenoceptor blockade.

This formulation is equally effective for treating conditions like angina pectoris, hypertension, and hyperthyroidism, while potentially improving patient adherence to treatment due to simplified dosing regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-acting propranolol (Inderal LA): pharmacokinetics, pharmacodynamics and therapeutic use. Mishriki, AA., Weidler, DJ.[2019]

Controlled-release formulations of propranolol, specifically Elanol and Inderal LA, provide smoother serum level profiles and delayed peak times compared to conventional propranolol, indicating a potentially more stable therapeutic effect.

Elanol showed greater bioavailability than Inderal LA, suggesting that long-acting formulations can be effective without the drawbacks of reduced bioavailability due to first-pass metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and pharmacodynamic studies with a new controlled-release formulation of propranolol in normal volunteers: a comparison with other commercially available formulations. Perucca, E., Grimaldi, R., Gatti, G., et al.[2019]

The study found that the nonselective beta-adrenergic antagonist propranolol effectively reversed CRF-induced defensive withdrawal behavior in rats, indicating its potential efficacy in modulating emotional responses.

Central beta 1-adrenergic receptors, rather than peripheral receptors, play a crucial role in mediating CRF-induced defensive withdrawal behavior, as shown by the significant effects of selective beta 1-antagonists administered directly into the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Central beta 1-adrenergic receptors are involved in CRF-induced defensive withdrawal. Yang, XM., Dunn, AJ.[2019]

Propranolol, a medication used to treat mild hypertension, was found to be less effective in cigarette smokers, suggesting that smoking may impair its antihypertensive action.

In contrast, bendrofluazide, another antihypertensive drug, maintained its efficacy regardless of smoking status, indicating that smoking does not affect its ability to lower blood pressure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The relationship between smoking and the response to anti-hypertensive treatment in mild hypertensives in the Medical Research Council's trial of treatment. Greenberg, G., Thompson, SG., Brennan, PJ.[2019]

In a study involving 9 smokers, labetalol, an adrenergic receptor blocker, significantly reduced the heart rate increase caused by nicotine, indicating its potential to mitigate some acute physiological effects of nicotine.

High-dose labetalol treatment also notably reduced tobacco withdrawal symptoms after nicotine administration, suggesting that adrenergic receptors play a role in these symptoms and highlighting the need for further research on using adrenergic blockers in smoking cessation therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Labetalol treatment enhances the attenuation of tobacco withdrawal symptoms by nicotine in abstinent smokers. Sofuoglu, M., Babb, D., Hatsukami, DK.[2015]

In a study involving 24 male smokers, the Nicoderm nicotine patch delivered significantly higher plasma nicotine concentrations compared to the Habitrol patch, especially in the first 8 hours after application.

Both patches had similar safety profiles, with no significant difference in the incidence of adverse events, but they were not bioequivalent, indicating that Nicoderm may provide a more effective nicotine delivery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the pharmacokinetics of two nicotine transdermal systems: nicoderm and habitrol. Gupta, SK., Okerholm, RA., Eller, M., et al.[2019]

Controlled, double-blind studies involving hospitalized volunteers found that propranolol hydrochloride did not alleviate or trigger opiate withdrawal symptoms in individuals dependent on heroin or dihydromorphinone.

Propranolol was ineffective in blocking the euphoria associated with heroin use and did not alter self-administration patterns in opiate-dependent subjects, contrasting with earlier uncontrolled reports suggesting its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of propranolol in opiate dependence. Resnick, RB., Kestenbaum, RS., Schwartz, LK., et al.[2019]

Clonidine and nortriptyline are recommended as second-line treatments for nicotine addiction, with nortriptyline showing efficacy due to its mechanism of norepinephrine reuptake inhibition, although side effects limit its use.

Emerging treatments like vaccines (NicVAX, CYT002-NicQb, and TA-NIC) are in early clinical trials and may prevent nicotine from reaching its receptors by inducing antibodies, showing promise for future nicotine addiction therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New trends in the treatment of nicotine addiction. Sliwińska-Mossoń, M., Zieleń, I., Milnerowicz, H.[2016]

The Committed Quitters Program (CQP) significantly improved quit rates among smokers who actively used the program materials, with 38.8% abstinence at 6 weeks and 18.2% at 12 weeks, compared to 30.7% and 11.1% in the standard User's Guide (UG) group.

Overall abstinence rates did not differ significantly between the CQP and UG groups, indicating that the effectiveness of CQP is particularly notable among those who engage with the tailored materials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy of computer-tailored smoking cessation material as a supplement to nicotine patch therapy. Shiffman, S., Paty, JA., Rohay, JM., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4410859/

Long-term Nicotine Replacement Therapy CONCLUSIONS AND RELEVANCE​​ The findings support the safety of long-term use of nicotine patch treatment, although they do not support efficacy beyond 24 weeks ...

2. acpjournals.org acpjournals.org/doi/10.7326/0003-4819-152-3-201002020-00005

Effectiveness of Extended-Duration Transdermal Nicotine ... This randomized trial of 568 long-term smokers found higher abstinence rates at 24 weeks for those who received extended nicotine therapy ( ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0376871600002374

The efficacy of computer-tailored smoking cessation ... As expected, among those who reported they used their assigned materials (80.1% of the sample) smokers who received CQP demonstrated higher quit rates at both 6 ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/8201739/

The effectiveness of the nicotine patch for smoking ... Active patch subjects were more than twice as likely to quit smoking as individuals wearing a placebo patch, and this effect was present at both high and low ...

5. hhs.texas.gov hhs.texas.gov/sites/default/files/documents/jan-2024-durb-agenda-item5ee.pdf

Smoking Cessation Agents Review The higher-dose preparations of nicotine gum, patch, and lozenge have been shown to be effective in highly-dependent smokers.

6. reference.medscape.com reference.medscape.com/drug/nicoderm-cq-nicotrol-nicotine-transdermal-999319

nicotine transdermal (OTC) Systemically absorbed; binds to nicotine receptors; reduces withdrawal symptoms (including nicotine craving) associated with smoking cessation.

7. haleonhealthpartner.com haleonhealthpartner.com/en-us/respiratory-health/brands/nicotine-replacement-therapy/nicoderm-cq/nicoderm-cq-safety-information/

NicoDerm CQ Clear Patch Safety Information NicoDerm CQ was generally well toleratedNicoDerm CQ was evaluated in 2 randomized studies comparing the 21 mg/24 hr patch with placebo (Study 1), and the 21 mg/ ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9575980/

Nicotine Patch Alters Patterns of Cigarette Smoking ... Participants were divided into low and high pack-years groups using a median split to assess the effects of nicotine dependence on smoking-induced dopamine ...