Nicotine Metabolite Ratio for Smoking Cessation

(QUIT Trial)

Overseen By Todd Takeno, MA

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Southcentral Foundation

Disqualifiers: Prior study, Recent cessation, Varenicline hypersensitivity, Bleeding disorder, Cancer treatment, others

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

Compensation: Varies

Number of Visits: 6

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to help Alaska Native and American Indian people quit smoking by using the Nicotine Metabolite Ratio (NMR) test. The NMR test guides doctors in selecting the best medication to assist participants in stopping smoking. Those who have smoked daily in the last 30 days, primarily use cigarettes, and plan to join a quit-smoking program soon are ideal candidates. Participants must provide a blood sample, be open to using medication, and have access to a smartphone with internet. As an unphased trial, this study offers participants the chance to contribute to important research that could enhance smoking cessation strategies for their communities.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It might be best to discuss this with the trial coordinators or your healthcare provider.

What prior data suggests that the Nicotine Metabolite Ratio is safe for smoking cessation?

Research shows that the Nicotine Metabolite Ratio (NMR) can enhance the safety of smoking cessation treatments. By understanding how quickly a person metabolizes nicotine, doctors can more effectively recommend appropriate medications. However, specific safety information about NMR itself is not available.

The NMR aids in selecting from FDA-approved smoking cessation medicines, which have been proven safe in other studies. Although direct safety data for NMR is lacking, the medicines chosen based on its results are known to be safe. This information can reassure those considering participation in the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using the Nicotine Metabolite Ratio (NMR) for smoking cessation because it offers a personalized approach to quitting smoking. Unlike standard treatments like nicotine replacement therapies or medications like varenicline, which are generally one-size-fits-all, the NMR test helps tailor treatment recommendations. By measuring how quickly a person's body metabolizes nicotine, it can guide doctors in choosing the most effective medication for each individual, potentially increasing the chances of successful quitting. This personalized strategy could make it easier for smokers to find the right support to kick the habit for good.

What evidence suggests that the Nicotine Metabolite Ratio is effective for smoking cessation?

Research shows that the Nicotine Metabolite Ratio (NMR) plays a crucial role in helping people quit smoking. In this trial, participants will receive the NMR test, and the results will guide medication recommendations for tobacco cessation. Studies have found that people who break down nicotine quickly face more challenges in quitting. By using NMR, researchers can identify who processes nicotine slowly or quickly and adjust treatments accordingly. For instance, those who process nicotine slowly might benefit more from certain medications, potentially improving their chances of quitting. One study found that treatments are 19% less effective for those who process nicotine quickly compared to those who do so slowly. This suggests that using NMR to guide treatment choices could help more people successfully quit smoking. ^{1 2 6 7 8}

Who Is on the Research Team?

Georgia J Michlig, PhD

Principal Investigator

Southcentral Foundation

Are You a Good Fit for This Trial?

This trial is for Alaska Native and American Indian individuals who are looking to quit smoking. Participants should be interested in using a personalized approach based on their body's metabolism of nicotine to select the best treatment.

Inclusion Criteria

Eligible for or already receiving services at Southcentral Foundation (SCF)

If other nicotine or tobacco products are used, cigarettes are main product used

Willing to provide a saliva sample

Exclusion Criteria

Participated in the prior study phase

Has history of serious hypersensitivity or skin reactions to varenicline

Participated in a cessation program during the past 3 months

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Beta Phase

Participants undergo the Nicotine Metabolite Ratio (NMR) test to inform medication recommendations for tobacco cessation

6 weeks

Multiple visits for testing and treatment recommendations

Pilot Phase

Participants continue with the intervention informed by NMR results to assess smoking cessation and intervention acceptability

26 weeks

Regular follow-up visits at 6, 12, and 26 weeks

Follow-up

Participants are monitored for smoking cessation and intervention effectiveness after the pilot phase

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Nicotine Metabolite Ratio

Trial Overview The study is testing an intervention that uses the Nicotine Metabolite Ratio (NMR) to choose the most suitable pharmacologic treatment aimed at helping participants stop smoking. It's a single-arm pilot trial focusing on how acceptable and doable this method is.

How Is the Trial Designed?

Group I: Nicotine Metabolite Ratio Experimental Treatment 1 Intervention

Subjects identified as cigarette smokers wishing to quit will receive the Nicotine Metabolite Ratio (NMR) test in a primary care setting and the results of the NMR will be used to inform medication recommendations for tobacco cessation.

Who Is Running the Clinical Trial?

Southcentral Foundation

Lead Sponsor

Trials

10

Recruited

8,000+

National Institute of General Medical Sciences (NIGMS)

Collaborator

Trials

315

Recruited

251,000+

Published Research Related to This Trial

The nicotine metabolite ratio (NMR) is a promising biomarker that can help tailor smoking cessation treatments to individual smokers, potentially improving their chances of quitting successfully.

Clinical trials suggest that slow metabolizers of nicotine benefit more from nicotine replacement therapy, while normal metabolizers respond better to non-nicotine treatments like varenicline, highlighting the importance of personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Precision Medicine for Tobacco Dependence: Development and Validation of the Nicotine Metabolite Ratio. Allenby, CE., Boylan, KA., Lerman, C., et al.[2023]

In a study of 185 smoking patients at a cardiology hospital, researchers classified individuals into slow and normal/fast metabolizers based on their nicotine metabolite ratio (NMR), with 55 identified as slow metabolizers and 130 as normal/fast.

The findings suggest that understanding a patient's NMR could help customize smoking cessation treatments, potentially improving success rates, although the study did not analyze the NMR's association with clinical characteristics during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the nicotine metabolite ratio in smoking patients treated with varenicline and bupropion. Tomaz, PRX., Gonçalves, TS., Santos, JR., et al.[2022]

In a study of 352 adult smokers, a higher nicotine metabolite ratio (NMR) was linked to increased daily puff volume and total puffs, suggesting that faster nicotine metabolism may lead to more intense smoking behavior.

The research also found that factors like race and gender influenced the relationship between NMR and smoking patterns, indicating that demographic factors may play a role in nicotine dependence and smoking habits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotine metabolite ratio predicts smoking topography: The Pennsylvania Adult Smoking Study. Chen, A., Krebs, NM., Zhu, J., et al.[2020]

Smoking cessation can significantly affect drug interactions due to the withdrawal of tobacco, which is a known inducer of the cytochrome P450 1A2 (CYP1A2) enzyme, leading to potential pharmacokinetic issues.

The study identified 245 substances that are CYP1A2 substrates, focusing on 63 with high reliability scores, providing a comprehensive list to help healthcare providers manage drug interactions effectively during smoking cessation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CYP1A2 and tobacco interaction: a major pharmacokinetic challenge during smoking cessation. Barrangou-Poueys-Darlas, M., Guerlais, M., Laforgue, EJ., et al.[2023]

In a study of 1,826 smokers attending Stop Smoking Services, it was found that Nicotine Metabolite Ratio (NMR) status, which indicates how quickly a person metabolizes nicotine, does not significantly vary across different sociodemographic characteristics, suggesting it could be a reliable measure for tailoring smoking cessation treatments.

Normal metabolizers of nicotine were less likely to use group behavioral support, indicating a potential area for further research to understand how NMR status influences the choice of support methods in smoking cessation programs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterising the nicotine metabolite ratio and its association with treatment choice: A cross sectional analysis of Stop Smoking Services in England. Shahab, L., Mortimer, E., Bauld, L., et al.[2019]

In a study of 499 smokers from the FLEX trial, the nicotine metabolite ratio, which reflects how quickly individuals metabolize nicotine, did not predict smoking cessation success when using nicotine replacement therapy or varenicline.

The findings suggest that adjusting nicotine replacement therapy based on the nicotine metabolite ratio may not enhance cessation outcomes, even among smokers with psychiatric conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotine metabolite ratio and smoking outcomes using nicotine replacement therapy and varenicline among smokers with and without psychiatric illness. Clyde, M., Pipe, A., Els, C., et al.[2019]

In a study of 180 Polish daily cigarette smokers, the average nicotine metabolite ratio (NMR) was found to be 4.8, indicating the rate of nicotine metabolism in this population.

Young women under 51 years had a significantly higher NMR of 6.4, suggesting they metabolize nicotine faster than other groups, which may require them to use higher doses of nicotine replacement therapy (NRT) for effective smoking cessation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Slower nicotine metabolism among postmenopausal Polish smokers. Kosmider, L., Delijewski, M., Koszowski, B., et al.[2021]

The nicotine metabolite ratio (NMR) showed excellent test-retest reliability in a study of 72 treatment-seeking smokers, indicating that NMR measurements are stable over a short period (2-3 weeks), which is important for tailoring smoking cessation treatments.

96% of participants maintained consistent classifications as slow or normal/fast metabolizers based on their NMR, suggesting that a single NMR assessment can effectively inform treatment strategies for smokers looking to quit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Test-Retest Reliability and Stability of the Nicotine Metabolite Ratio Among Treatment-Seeking Smokers. Hamilton, DA., Mahoney, MC., Novalen, M., et al.[2018]

The nicotine metabolite ratio (NMR) is a validated biomarker that helps tailor smoking cessation treatments to individual smokers, potentially leading to better outcomes.

Further research is needed to explore the NMR's effectiveness in predicting responses to various nicotine delivery methods, including e-cigarettes, and to assess its cost-effectiveness in diverse populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Use of the Nicotine Metabolite Ratio as a Biomarker to Personalize Smoking Cessation Treatment: Current Evidence and Future Directions. Siegel, SD., Lerman, C., Flitter, A., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4558221/

Rate of Nicotine Metabolism and Smoking Cessation ... In a community-based sample of treatment-seeking smokers, faster nicotine metabolizers were significantly less likely to quit smoking and showed higher rates ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0306460315002750

Rate of Nicotine Metabolism and Smoking Cessation ... Faster nicotine metabolizers were significantly less likely to quit smoking and showed higher rates of anxiety symptoms during a smoking cessation treatment ...

3. nature.com nature.com/articles/s41598-017-17994-8

Characterising the nicotine metabolite ratio and its ... Pharmacotherapy provision based on Nicotine Metabolite Ratio (NMR) status (slow/normal metabolism) may improve smoking cessation rates.

4. tandfonline.com tandfonline.com/doi/full/10.1080/17476348.2024.2429675?scroll=top&needAccess=true

Full article: Is the nicotine metabolite ratio a useful tool to ... Taking into account these reasons, we can conclude that smoking cessation treatments in fast metabolizers reduce their efficacy by 19% in comparison with slow ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6492100/

Does the nicotine metabolite ratio moderate smoking ... Similarly, data on the association of NMR with smoking cessation outcomes are mixed. Studies of pharmacological treatments have shown that slow metabolizers ...

6. withpower.com withpower.com/trial/phase-smoking-cessation-7-2024-76bdf

Nicotine Metabolite Ratio for Smoking Cessation (QUIT Trial) Is the Nicotine Metabolite Ratio (NMR) safe for use in humans? The available research does not provide specific safety data for the Nicotine Metabolite Ratio ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2772632024000394

The impact of rate of nicotine metabolism, as measured by ... The nicotine metabolite ratio (NMR), the ratio between 3-hydroxycotinine and cotinine, indicates the rate of nicotine metabolism and is associated with smoking ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03227679

Metabolism-informed Care for Smoking Cessation This intervention used information from a genetically-informed biomarker (Nicotine Metabolite Ratio, NMR) to assign one of 3 FDA-approved smoking cessation ...