Tailored Smoking Cessation Therapy for Smoking Addiction

Overseen By Stephen M King

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Vanderbilt-Ingram Cancer Center

Must be taking: Varenicline, Nicotine replacement

Disqualifiers: Low English proficiency, Cognitive impairment, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to help people quit smoking through a personalized approach called Metabolism-Informed Smoking Treatment (MIST). The approach matches the right medication with how a person's body processes nicotine, using either Nicotine Replacement Therapy (such as nicotine gum, lozenge, patch, inhaler, or nasal spray) or Varenicline (also known as Chantix or Champix). Participants receive support through phone calls after leaving the hospital to help them stay on track. Daily smokers planning to quit and eligible to use these medications could be a good fit for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if 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?

Studies have shown that the treatments used in the Metabolism-Informed Smoking Treatment (MIST) trial, Nicotine Replacement Therapy (NRT) and varenicline, are generally safe for people.

Research indicates that NRT, which manages cravings and withdrawal symptoms by providing nicotine without smoking, is usually well-tolerated. Minor side effects, such as skin irritation from patches, can occur.

For varenicline, studies found that it significantly aids smoking cessation. Some individuals experience side effects, with nausea and headaches being the most common. Despite these, varenicline is considered safe for many users.

Both treatments have been used in previous studies and are approved for helping people stop smoking. This suggests they are safe options for those considering joining this trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for smoking addiction?

Researchers are excited about this trial because it explores a more personalized approach to smoking cessation. Unlike the standard care that doesn't consider nicotine metabolism, the MIST (Metabolism-Informed Smoking Treatment) arm tailors medication based on how quickly a person metabolizes nicotine. This means faster metabolizers receive varenicline, while slower metabolizers are given nicotine replacement therapy (NRT). This personalized strategy could potentially enhance the effectiveness of the treatment, offering a more targeted way to help individuals quit smoking.

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

Research has shown that customizing smoking treatments based on how quickly a person processes nicotine can be very effective. One study found that people who break down nicotine faster are less likely to quit smoking unless their treatment is adjusted to their metabolism. This is where the Metabolism-Informed Smoking Treatment (MIST), one of the treatment arms in this trial, plays a role. It uses a measure called the Nicotine Metabolite Ratio (NMR) to help choose the best treatment.

In this trial, participants in the MIST arm will receive either Nicotine Replacement Therapy (NRT) or Varenicline, based on their nicotine metabolism. NRT can boost the chances of quitting by 50%. Varenicline, another option in this trial, has shown high effectiveness, with about 44% of people successfully quitting in some studies. When these treatments match a person's nicotine metabolism, they may lead to better success in quitting smoking. ^{2 3 6 7 8}

Who Is on the Research Team?

Hilary Tindle, MD, MPH

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

This trial is for daily smokers over 18 with a regular healthcare provider, who are willing to try quitting smoking after hospital discharge. They must be able to use nicotine replacement or varenicline, have phone access, a permanent address, and prescription coverage. Those too ill, in hospice care, not cognitively able to participate or already in another smoking study can't join.

Inclusion Criteria

have a regular provider/PCP

I can safely use nicotine replacement therapy.

have a cell phone or landline that can be reached directly (i.e., without transfer)

Exclusion Criteria

insufficient time to perform and complete the enrollment process

barrier to effective communication (including low English proficiency)

I am too sick, in hospice care, or unable to follow up as required.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either MIST or Usual Care interventions, with medication prescriptions tailored or not tailored to nicotine metabolism

6 months

Automated phone calls post-discharge

Follow-up

Participants are monitored for abstinence and clinical practice implementation at 6 and 12 months

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Metabolism Informed Smoking Treatment (Nicotine metabolite ratio (NMR)-based selection of pharmacotherapy)
• Nicotine Replacement Therapy
• Post-discharge automated phone calls (IVR) with option to connect with a tobacco coach
• Varenicline

Trial Overview The MIST RCT is testing tailored smoking cessation treatments based on how fast individuals metabolize nicotine. Participants will receive either standard Nicotine Replacement Therapy or Varenicline guided by their Nicotine Metabolite Ratio (NMR), along with automated follow-up calls and tobacco coaching.

How Is the Trial Designed?

Group I: MIST (Metabolism-Informed Smoking Treatment) Experimental Treatment 4 Interventions

At hospital discharge, participants randomized to the MIST precision care arm will receive a prescription for medication (either varenicline or NRT). Post discharge, participants will receive automated phone calls via TelASK to promote continued engagement. Medication prescriptions will be informed by nicotine metabolism (i.e., NMR result) such that faster metabolizers are prescribed varenicline and slower metabolizers are prescribed NRT.

Group II: Usual Care Active Control 3 Interventions

At hospital discharge, participants randomized to the Usual Care arm will receive a prescription for medication (either varenicline or NRT). Post discharge, participants will receive automated phone calls via TelASK to promote continued engagement. Medication prescription will not be informed by nicotine metabolism.

Nicotine Replacement Therapy is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as NRT for:

• Smoking cessation

Approved in European Union as NRT for:

• Smoking cessation

Approved in Canada as NRT for:

• Smoking cessation

Approved in Japan as NRT for:

• Smoking cessation

Who Is Running the Clinical Trial?

Vanderbilt-Ingram Cancer Center

Lead Sponsor

Trials

221

Recruited

64,400+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6236077/

Nicotine Metabolism-informed Care for Smoking Cessation MIC, an NMR-based precision approach to smoking cessation, was acceptable to 90% of smokers and improved NMR-medication match rates more than 3-fold compared ...

2. 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 ...

3. 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 ...

4. archpublichealth.biomedcentral.com archpublichealth.biomedcentral.com/articles/10.1186/s13690-024-01365-7

Implementing a Metabolism-informed approach for smoking ... NMR is a metabolism-informed biomarker that can be used to guide medication selection. NMR testing is particularly promising for tobacco ...

5. 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 ...

6. researchgate.net researchgate.net/publication/320593359_Nicotine_Metabolism-informed_Care_for_Smoking_Cessation_A_Pilot_Precision_RCT

Nicotine Metabolism-informed Care for Smoking Cessation Metabolism-informed care (MIC) could improve outcomes by matching normal metabolizers with non-nicotine medication (e.g., varenicline) and slow ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2772392523000160

The use of biomarkers to guide precision treatment for ... This review summarizes the evidence to date on the development of biomarkers for personalizing the pharmacological treatment of combustible tobacco use.

8. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0230656

Precision nicotine metabolism-informed care for smoking ... The nicotine metabolite ratio (NMR) predicts cessation success with pharmacotherapy: varenicline doubles cessation over nicotine replacement ...