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

Trial Summary

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 data supports the effectiveness of the treatment Nicotine Metabolite Ratio for smoking cessation?

Research suggests that the nicotine metabolite ratio (NMR) can help personalize smoking cessation treatments by identifying whether a person is a slow or normal/fast metabolizer of nicotine. This can guide the choice of treatment, such as using nicotine replacement therapy for slow metabolizers and non-nicotine treatments like varenicline for normal metabolizers, potentially improving the chances of quitting smoking. ^{1 2 3 4 5}

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 (NMR) itself, as it is primarily used as a measure to tailor smoking cessation treatments rather than a treatment on its own. ^{2 4 6 7 8}

How does the nicotine metabolite ratio treatment differ from other smoking cessation treatments?

The nicotine metabolite ratio (NMR) treatment is unique because it uses a biomarker to measure how quickly a person metabolizes nicotine, allowing for personalized smoking cessation plans. This approach can help determine whether nicotine replacement therapy or non-nicotine treatments like varenicline are more suitable, based on individual metabolism rates. ^{1 2 3 6 9}

What is the purpose of this trial?

The purpose of this study is to refine and pilot an intervention using the Nicotine Metabolite Ratio (NMR) to inform the selection of pharmacologic treatment to increase smoking abstinence among Alaska Native and American Indian people. This is a single-arm pilot trial to assess and improve acceptability and feasibility.

Research Team

Georgia J Michlig, PhD

Principal Investigator

Southcentral Foundation

Eligibility Criteria

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)

I am willing to try drug treatment.

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

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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 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]

References

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

Test-Retest Reliability and Stability of the Nicotine Metabolite Ratio Among Treatment-Seeking Smokers. [2018]

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

Nicotine metabolite ratio and smoking outcomes using nicotine replacement therapy and varenicline among smokers with and without psychiatric illness. [2019]

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

Precision Medicine for Tobacco Dependence: Development and Validation of the Nicotine Metabolite Ratio. [2023]

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

Evaluation of the nicotine metabolite ratio in smoking patients treated with varenicline and bupropion. [2022]

5. United States 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. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Slower nicotine metabolism among postmenopausal Polish smokers. [2021]

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

CYP1A2 and tobacco interaction: a major pharmacokinetic challenge during smoking cessation. [2023]

8. England 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. [2019]

9. Ireland pubmed.ncbi.nlm.nih.gov

Nicotine metabolite ratio predicts smoking topography: The Pennsylvania Adult Smoking Study. [2020]