Genotype-Guided Smoking Cessation Therapy for Coronary Artery Disease

Recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Washington University School of Medicine

Must be taking: Nicotine replacement

Disqualifiers: Incarcerated, Pregnancy, Breastfeeding, others

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

Compensation: Varies

Number of Visits: 6

Duration: 12 weeks

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to help people with coronary artery disease quit smoking. Researchers aim to determine if a person's genetic information can guide the best treatment, whether through counseling or nicotine patches. This method is known as genotype-guided therapy. The study compares these personalized treatments to standard methods that do not use genetic information. Adults who smoke and have coronary artery disease, particularly those who have recently had a heart attack, might be suitable candidates for this trial. As an unphased study, this trial offers a unique opportunity to contribute to innovative research that could lead to more personalized treatment options for quitting smoking.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found that a treatment plan based on a person's genes helped reduce the risk of heart problems, such as heart attacks and strokes, in patients with coronary artery disease. This finding suggests that adjusting treatment according to genetic information can be safe and effective for managing the condition.

For those using the nicotine patch to quit smoking, research has shown it is generally safe, even for people with heart disease. One study found that the nicotine patch did not worsen heart health in patients with coronary artery disease. Another study confirmed that using the patch did not lead to more heart problems in the short term.

In summary, both the gene-based treatment and the nicotine patch have demonstrated promising safety records in past studies, indicating they are likely to be well-tolerated by people with coronary artery disease. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about genotype-guided smoking cessation therapy because it personalizes treatment based on a person's genetic makeup. Unlike standard options like nicotine patches or counseling, which are the same for everyone, this approach tailors the method to the individual's CHRNA5 gene variant. This could potentially enhance effectiveness by targeting the biological factors influencing smoking habits. By incorporating genetic information, this method might offer more precise and successful quitting strategies for patients with coronary artery disease.

What evidence suggests that this trial's treatments could be effective for coronary artery disease?

Research has shown that genetic information can help create personalized treatments for quitting smoking in people with heart disease. Some participants in this trial will receive genotype-guided therapy, where genetic information tailors smoking cessation treatment. For instance, GG homozygotes will receive smoking cessation counseling, while A allele carriers will receive pharmacologic therapy with nicotine replacement therapy (NRT), such as nicotine patches.

Studies have found that nicotine patches more than double the chances of quitting smoking compared to not using them. They are also safe for people with heart disease and do not increase heart-related risks. These findings suggest that using genetic information to guide treatment with nicotine patches could effectively help those with heart disease quit smoking. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for adults with coronary artery disease undergoing cardiac catheterization or who have had a heart attack, and are active smokers. They must be able to consent, not incarcerated, stable post-heart attack without life-threatening complications, and women of child-bearing age should not be pregnant or breastfeeding.

Inclusion Criteria

I was admitted to Barnes hospital for a heart attack or have coronary artery disease.

You are already taking part in the PRISM-GENOMICS observational study.

You are currently smoking when you come to Barnes Hospital.

Exclusion Criteria

I have had serious complications from a heart attack.

I am unable to understand and give consent for treatment.

I am currently unable to communicate verbally.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Genotyping and Initial Treatment

Participants are genotyped and receive genotype-guided or standard smoking cessation therapy

2 weeks

1 visit (in-person)

Treatment

Participants continue with either pharmacologic therapy or counseling based on their assigned group

12 weeks

4 visits (virtual)

Follow-up

Participants are monitored for smoking cessation success and safety

12 months

Quarterly telephone-administered questionnaires

What Are the Treatments Tested in This Trial?

Interventions

• genotype-guided therapy
• Nicotine patch
• Smoking cessation counseling

Trial Overview The study tests if nicotine patches and genotype-guided therapy can help patients quit smoking more effectively than standard treatments. Patients' genetic profiles determine their treatment plan in this randomized study.

How Is the Trial Designed?

Group I: Genotype-guided (GG homozygotes) Experimental Treatment 2 Interventions

CHRNA5 rs16969968 genotype will be determined. Genotype-guided therapy will be given (GG homozygotes will be given smoking cessation counseling)

Group II: Genotype-guided (A allele carriers) Experimental Treatment 2 Interventions

CHRNA5 rs16969968 genotype will be determined. Genotype-guided therapy will be given (A allele carriers will be given pharmacologic therapy (nicotine replacement therapy --NRT; nicotine patch used according to FDA labelling).)

Group III: Standard (non-genotype guided) - NRT Active Control 1 Intervention

1/2 of patients in this arm will be given nicotine replacement therapy (NRT; nicotine patch used according to FDA labeling) but this will NOT be based on the patient's genotype. Note that both nicotine replacement therapy and counseling are accepted treatments for smoking cessation in patients with coronary artery disease.

Group IV: Standard (non-genotype guided)- counseling Active Control 1 Intervention

1/2 of patients in this arm will be given smoking cessation counseling but this will NOT be based on the patient's genotype. Note that both nicotine replacement therapy and counseling are accepted treatments for smoking cessation in patients with coronary artery disease.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Published Research Related to This Trial

Nicotine replacement therapy (NRT) is effective for smoking cessation, but many users do not achieve long-term abstinence, suggesting a need for personalized treatment approaches.

Tailoring NRT to individual smokers' needs and preferences, potentially using genetic profiling, could improve treatment outcomes and safety, addressing the variability in response to standard NRT formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tailoring nicotine replacement therapy: rationale and potential approaches. McClure, JB., Swan, GE.[2018]

The study found that three prototype 4-mg nicotine lozenges produced in India were bioequivalent to the globally marketed Nicorette® 4-mg lozenge, indicating they can effectively deliver similar levels of nicotine to the bloodstream.

All prototype lozenges were well tolerated and had safety profiles comparable to the reference product, suggesting they are a safe alternative for nicotine replacement therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic characterization of three novel 4-mg nicotine lozenges . Sukhija, M., Srivastava, R., Kaushik, A.[2018]

High-dose transdermal nicotine-replacement therapy (NRT) at doses of 42 mg or more daily appears to be safe, with most trials reporting no serious adverse events, although a dose-response relationship for adverse events was noted.

While high-dose NRT showed a numerically higher abstinence rate in most trials, none achieved statistically significant differences in final abstinence rates, indicating that more extensive studies are needed to confirm its efficacy and identify suitable patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose transdermal nicotine replacement for tobacco cessation. Brokowski, L., Chen, J., Tanner, S.[2019]

Citations

1. withpower.com withpower.com/trial/phase-myocardial-ischemia-6-2015-6fb3e

Genotype-Guided Smoking Cessation Therapy for ... This trial tests if using genetic information to guide smoking cessation treatment can help patients with coronary artery disease quit smoking more ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5115988/

Pathways to Precision Medicine in Smoking Cessation ... These data suggest that genetic risks may predict smoking cessation outcomes and moderate the effect of pharmacological treatments. Some pharmacogenetic ...

3. frontiersin.org frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2023.1105001/full

Influence of CYP2C19 genetic variants and smoking on ... This study aimed to investigate the effects of smoking and CYP2C19 gene polymorphism on antiplatelet therapy to specify the most optimized and accurate ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1936879817314991

Multisite Investigation of Outcomes With Implementation ... This multicenter pragmatic investigation assessed outcomes following clinical implementation of CYP2C19 genotype–guided antiplatelet therapy ...

5. journals.lww.com journals.lww.com/md-journal/fulltext/2025/06130/pharmacogenomics_and_risk_stratification_in.52.aspx

Pharmacogenomics and risk stratification in cardiovascular... This narrative review examines randomized clinical trials (RCTs) on genotype-guided therapies, pharmacogenomics, and personalized medicine in cardiology.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11512840/

Impact of CYP2C19 Genotype Status on Clinical Outcomes ... Genotype-guided treatment significantly decreased the rate of atherothrombotic events in patients with CAD, especially after PCI.

7. jacc.org jacc.org/doi/10.1016/j.jcin.2021.02.005

Genotype-Guided Antiplatelet Therapy in Patients With ... The primary efficacy endpoint was the composite of cardiovascular death, myocardial infarction, stroke, stent thrombosis, and severe recurrent ischemia; the ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06665919

NCT06665919 | The Study of CYP2C19 Genotype-Guided ... The study purposed to learn how clopidogrel-based antiplatelet treatment for preventing adverse cardiovascular events after ePCI works in chronic coronary ...

9. ahajournals.org ahajournals.org/doi/10.1161/JAHA.121.024159

CYP2C19 Genotype‐Guided Antiplatelet Therapy After ... Real‐world data demonstrate lower atherothrombotic risk in CYP2C19 LOF carriers treated with alternative therapy versus clopidogrel and similar risk in those ...

10. sciencedirect.com sciencedirect.com/science/article/pii/S0735109724078938

Genotype-Guided Antiplatelet Therapy: JACC Review ... Multiple studies have assessed the efficacy and safety of a CYP2C19 genotype–guided strategy in patients with atherosclerotic coronary artery disease (CAD) ( ...