Genotype-Guided Smoking Cessation Therapy for Coronary Artery Disease

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

Trial Summary

What is the purpose of this trial?

This trial tests if using genetic information to guide smoking cessation treatment can help patients with coronary artery disease quit smoking more effectively. Patients will receive either nicotine replacement therapy or counseling based on their genetic test results.

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.

What data supports the effectiveness of the treatment for smoking cessation in patients with coronary artery disease?

Research suggests that tailoring nicotine replacement therapy (NRT) based on genetic information can improve adherence and potentially increase the success rates of quitting smoking. Studies indicate that understanding genetic factors influencing nicotine metabolism and addiction can help personalize treatment, making it more effective for individuals. ^{1 2 3 4 5}

Is genotype-guided smoking cessation therapy safe for people with coronary artery disease?

Research shows that nicotine replacement therapy (NRT), including nicotine patches, is generally safe for smokers hospitalized with coronary heart disease. A study found no difference in short-term outcomes like mortality or hospital readmission between those who used NRT and those who did not. ^{2 6 7 8 9}

How is genotype-guided therapy with a nicotine patch unique for smoking cessation in coronary artery disease?

This treatment is unique because it uses genetic information to tailor the nicotine patch dosage specifically to an individual's DNA, potentially improving adherence and effectiveness compared to standard treatments that do not consider genetic differences. ^{1 2 5 6 10}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Pharmacogenetics factors influencing smoking cessation success; the importance of nicotine metabolism. [2022]

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

Trial Protocol: Using genotype to tailor prescribing of nicotine replacement therapy: a randomised controlled trial assessing impact of communication upon adherence. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Pharmacogenetics and nicotine addiction treatment. [2013]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Genetics and smoking cessation improving outcomes in smokers at risk. [2021]

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

Pharmacogenetics and smoking cessation with nicotine replacement therapy. [2018]

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

Tailoring nicotine replacement therapy: rationale and potential approaches. [2018]

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

High-dose transdermal nicotine replacement for tobacco cessation. [2019]

8. Germany pubmed.ncbi.nlm.nih.gov

Pharmacokinetic characterization of three novel 4-mg nicotine lozenges . [2018]

9. England pubmed.ncbi.nlm.nih.gov

Short-Term Safety of Nicotine Replacement in Smokers Hospitalized With Coronary Heart Disease. [2021]

10. Ireland pubmed.ncbi.nlm.nih.gov

The association of rs1051730 genotype on adherence to and consumption of prescribed nicotine replacement therapy dose during a smoking cessation attempt. [2022]