Varenicline + Guanfacine for Smoking Cessation

Overseen By Sabrina Coppola

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Yale University

Must not be taking: Antihypertensives, CNS depressants

Disqualifiers: Hypertension, Seizures, Severe mental illness, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

165 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 quit smoking by combining two medications, varenicline and guanfacine ER (an extended-release medication), to assess their combined effectiveness. The goal is to understand how these drugs can reduce the urge to smoke, especially under stress, over a 12-week period. The trial compares individuals taking both medications with those taking only varenicline. It seeks participants who have smoked at least 10 cigarettes daily for the past year and are motivated to quit. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stop taking medications known to be effective for smoking cessation and certain other medications like antihypertensives and CNS depressants. If you're on these, you may need to stop them to participate.

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

Research shows that varenicline is generally well-tolerated by people trying to quit smoking. Some studies have found that it can cause side effects like nausea or headaches, but these are usually mild and manageable. The FDA has approved varenicline for helping people stop smoking, indicating it has passed safety checks for this use.

Guanfacine is typically used to treat high blood pressure and ADHD (attention-deficit/hyperactivity disorder). It has been found to help reduce stress and might also aid in smoking cessation. Some studies have linked guanfacine to side effects like drowsiness and dry mouth, but these are generally mild.

Researchers are testing the combination of varenicline and guanfacine to see if it can help people quit smoking more effectively. Early research suggests this combination might be safe, but ongoing studies are checking for any new safety concerns. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining Varenicline with Guanfacine ER for smoking cessation because it offers a unique approach that targets both the chemical addiction and the behavioral aspects of smoking. Varenicline works by partially activating nicotine receptors in the brain, reducing cravings and withdrawal symptoms, while Guanfacine ER is thought to enhance impulse control and reduce stress, which are key triggers for smoking. This dual-action strategy aims to provide a more comprehensive solution than current options, which typically focus on nicotine replacement or single-agent therapies. By addressing both the physical and psychological components of smoking addiction, this combination has the potential to improve quit rates and long-term success for individuals trying to quit smoking.

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

Research has shown that using Varenicline and Guanfacine together might help people quit smoking. In this trial, some participants will receive a combination of Varenicline and Guanfacine. One study found that Guanfacine alone helped 42% of participants quit smoking, compared to 19% who took a placebo (a pill with no active ingredients). Varenicline is already known to help people stop smoking; another study showed that 44% of people were able to quit. This trial will compare the effectiveness of Varenicline alone to the combination of Varenicline and Guanfacine, aiming to improve smoking cessation outcomes. ^{1 2 6 7 8}

Who Is on the Research Team?

Sherry McKee, PhD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for adults who've smoked 10+ cigarettes daily for the past year, have a CO level >10 ppm, are motivated to quit smoking, and can commit to the study duration. They must be stable residents with transport and no plans to move soon. Excluded are those with significant medical conditions, substance use disorders (except mild alcohol/tobacco), recent psychoactive drug use, severe mental illness or ADHD.

Inclusion Criteria

SMOKER: 10 or more cigarettes per day for at least the past year, Carbon Monoxide (CO) > 10 ppm at intake

Able to read and write English

I can take pills and will follow the medication plan.

Exclusion Criteria

Meeting DSM-V criteria for current (past-6 month) attention deficit hyperactivity disorder (ADHD)

Only one member per household can participate in the study

I have not had severe mental health issues like schizophrenia or bipolar disorder in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Titration

Participants titrate to steady state levels of Varenicline and Guanfacine

3 weeks

Multiple visits for dose adjustment

Treatment

Participants receive Varenicline and Guanfacine for smoking cessation

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Guanfacine ER
• Varenicline

Trial Overview The study tests combining Varenicline and Guanfacine ER to help people stop smoking. It includes a lab phase assessing stress-related smoking behavior followed by a 12-week treatment phase for clinical outcomes.

How Is the Trial Designed?

Group I: Varenicline + Guanfacine ER Experimental Treatment 2 Interventions

Varenicline (2mg/day) + Guanfacine extended release (6mg/day ER). Varenicline (2mg/day) administered orally twice a day at 8:00 AM and 8:00 PM while titrating to full dose. Titration schedule: Days 1-9 0mg/day; 0mg/dose, Days 10-12 0.5mg/day; 0.5mg/dose 8:00 PM, Days 13-15 1mg/day; 0.5mg/dose, Days 16-21 2mg/day; 1mg/dose. Guanfacine ER (6mg/day) administered orally twice daily at 8:00 AM and 8:00 PM while titrating to the full dose. Titration schedule: Days 1-3 1mg/day; 0.5mg/dose, Days 4-6 2mg/day; 1mg/dose, Days 7-9 3mg/day; 1.5mg/dose, Days 10-12 4mg/day; 2mg/dose; Days 13-15 5mg/day; 2.5mg/dose and Days 16-23 6mg/day; 3mg/dose. Once at steady state, administration is orally once per day at 8:00 PM for both medications.

Group II: Varenicline Active Control 1 Intervention

Varenicline (2mg/day). Varenicline (2mg/day) administered orally twice a day at 8:00 AM and 8:00 PM while titrating to full dose. Titration schedule: Days 1-9 0mg/day; 0mg/dose, Days 10-12 0.5mg/day; 0.5mg/dose 8:00 PM, Days 13-15 1mg/day; 0.5mg/dose, Days 16-21 2mg/day; 1mg/dose. Once at steady state, administration is orally once per day at 8:00 PM.

Guanfacine ER is already approved in United States, European Union for the following indications:

Approved in United States as Tenex for:

• Hypertension

Approved in United States as Intuniv for:

• Attention Deficit Hyperactivity Disorder (ADHD)

Approved in European Union as Intuniv for:

• Attention Deficit Hyperactivity Disorder (ADHD)

Approved in European Union as Paxneury for:

• Attention Deficit Hyperactivity Disorder (ADHD)

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

In a study of 148 outpatients, varenicline showed increasing smoking cessation rates with longer treatment durations, achieving an 84.6% abstinence rate in those treated for 9 to 12 weeks.

Patients experiencing adverse events had varying abstinence rates, with the highest success in those receiving active nosotropic medication, suggesting that maintaining regular dosage for 12 weeks can enhance treatment efficacy even in patients with side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Sustainable efficacy of oral varenicline for smoking cessation]. Onizawa, S., Taniguchi, H., Nozu, T., et al.[2015]

In a randomized controlled trial, varenicline (Chantix) demonstrated a higher abstinence rate from smoking after one year compared to both bupropion SR (Zyban) and a placebo, indicating its efficacy in treating tobacco dependence.

Despite its effectiveness, varenicline has been associated with serious neuropsychiatric side effects, highlighting the importance of discussing potential risks and benefits with patients considering this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of nicotine dependence with Chantix (varenicline). Rankin, KV., Jones, DL.[2015]

Varenicline, an FDA-approved medication for smoking cessation, significantly increases the chances of quitting smoking, with continuous abstinence rates 2.7 to 3.1 times higher than placebo over a 52-week period after 12 weeks of treatment.

In addition to helping smokers quit, varenicline reduces cravings and withdrawal symptoms, making it a valuable option for those looking to stop smoking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Varenicline: a review of its use as an aid to smoking cessation therapy. Keating, GM., Siddiqui, MA.[2018]

Varenicline is a highly effective medication for smoking cessation, showing superior efficacy compared to placebo and bupropion in clinical trials involving chronic smokers, and it helps alleviate withdrawal symptoms.

The recommended treatment regimen involves starting varenicline one week before the quit date, with a titration schedule to minimize side effects like nausea, making it a suitable option for smokers who struggle with other cessation aids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Varenicline: a selective alpha4beta2 nicotinic acetylcholine receptor partial agonist approved for smoking cessation. Lam, S., Patel, PN.[2017]

In a study of 1027 adult smokers, varenicline was found to be significantly more effective for smoking cessation than both placebo and bupropion SR, with 43.9% of participants abstinent during the last 4 weeks of treatment compared to 17.6% and 29.8% respectively.

Varenicline was generally safe and well-tolerated, with the most common side effect being nausea, affecting 29.4% of participants, and a discontinuation rate due to adverse events similar to that of bupropion SR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial. Jorenby, DE., Hays, JT., Rigotti, NA., et al.[2023]

In a phase 2 study involving 411 healthy smokers, varenicline tartrate at doses of 1.0 mg once and twice daily significantly increased quit rates compared to placebo, with 48.0% and 37.3% quitting respectively, versus only 17.1% for placebo.

Varenicline was well tolerated, with discontinuation rates due to adverse events similar to placebo, indicating it is a safe and effective option for smoking cessation, especially at the 1.0 mg twice daily dose for long-term success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Smoking cessation with varenicline, a selective alpha4beta2 nicotinic receptor partial agonist: results from a 7-week, randomized, placebo- and bupropion-controlled trial with 1-year follow-up. Nides, M., Oncken, C., Gonzales, D., et al.[2022]

In a study of 3569 smokers, those using varenicline had a significantly higher sustained abstinence rate (15.2%) compared to those using combination nicotine replacement treatment (cNRT) (10.3%) over a 12-month period, indicating that varenicline may be more effective for long-term smoking cessation.

The study highlights that varenicline's effectiveness was observed in a real-world setting, where participants chose their treatment and received structured support, suggesting that it could be a preferred option for smoking cessation programs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of Varenicline Versus Combination Nicotine Replacement Therapy for Smoking Cessation: One-Year Outcomes in a Smoking Cessation Clinic in Taiwan. Hsueh, KC., Tang, PL., McRobbie, H.[2021]

In a real-world study involving 566 participants across four European countries, varenicline was found to be an effective smoking cessation aid, with a 64.6% quit rate by the end of the 12-week treatment period.

The safety profile of varenicline was acceptable, with the most common side effects being mild to moderate nausea (8.9%) and insomnia (2.9%), and only 3.4% of participants discontinued due to treatment-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of varenicline as an aid to smoking cessation: results of an inter-European observational study. Boudrez, H., Gratziou, C., Messig, M., et al.[2015]

In a study of 2,682 patients using varenicline for smoking cessation, nausea and vomiting were the most common reasons for discontinuation and the most frequently reported adverse drug reactions, highlighting the need for patient monitoring regarding gastrointestinal side effects.

While some psychiatric events were reported, including anxiety and depression, all cases of suicidal behavior involved patients with prior psychiatric conditions, suggesting that clinicians should closely monitor individuals with such histories when prescribing varenicline.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and drug utilization profile of varenicline as used in general practice in England: interim results from a prescription-event monitoring study. Kasliwal, R., Wilton, LV., Shakir, SA.[2021]

Varenicline (VAR) is effective in promoting smoking cessation by partially substituting for and blocking the reinforcing effects of nicotine, as shown in a study with rats that assessed various doses of VAR.

Moderate doses of VAR (0.1 and 1.0 mg/kg) increased the number of visual stimulus presentations earned by rats, while also attenuating the reinforcement-enhancing effects of nicotine, indicating its potential as a therapeutic agent in smoking cessation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Varenicline dose dependently enhances responding for nonpharmacological reinforcers and attenuates the reinforcement-enhancing effects of nicotine. Levin, ME., Weaver, MT., Palmatier, MI., et al.[2021]

Varenicline (Champix) is a newly approved medication for smoking cessation that acts as a partial agonist of nicotinic receptors, offering a different mechanism of action compared to traditional therapies like nicotine replacement and bupropion.

Recent studies indicate that varenicline is effective in helping individuals quit smoking and may have advantages over existing treatments, although potential side effects are also discussed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Drug of the month. Varenicline (Champix)]. Vandemergel, X.[2015]

Citations

1. reporter.nih.gov reporter.nih.gov/project-details/10398931

Varenicline + Guanfacine - NIH RePORTER In a randomized clinical trial, we found that guanfacine significantly increased smoking cessation (42% vs. 19% placebo; end-of-treatment point prevalence), and ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04198116

Combining Varenicline and Guanfacine for Smoking ... This Phase 2 study will randomize 140 smokers to a parallel group design (varenicline + guanfacine vs. varenicline alone).

3. app.trialscreen.org app.trialscreen.org/trials/phase-2-smoking-cessation-combining-varenicline-guanfacine-trial-nct04198116

Combining Varenicline and Guanfacine for Smoking ... Benefits: Participation in this study may help individuals quit smoking, which can lead to improved overall health and reduced risk of smoking-related diseases.

4. medicine.yale.edu medicine.yale.edu/yigh/trial/combining-varenicline-and-guanfacine-for-smoking-cessation/

Combining Varenicline and Guanfacine for Smoking Cessation In this study, we are looking at how the medications Varenicline and Guanfacine can be used to treat smoking.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4824380/

Varenicline for smoking cessation: a narrative review of ... Both studies had similarly significant results with 44% abstinence in the varenicline group compared with 30% in the bupropion group, and 18% in the placebo ...

6. yalemedicine.org yalemedicine.org/clinical-trials/combining-varenicline-and-guanfacine-for-smoking-cessation

Combining Varenicline and Guanfacine for Smoking ... In this study, we are looking at how the medications Varenicline and Guanfacine can be used to treat smoking.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2962400/

Varenicline for smoking cessation: efficacy, safety, and ... These studies indicate that comprehensive insurance coverage for tobacco dependence treatment can have a positive effect on smoking abstinence outcomes. No ...

8. medicine.yale.edu medicine.yale.edu/trial/combining-varenicline-and-guanfacine-for-smoking-cessation/

Combining Varenicline and Guanfacine for Smoking Cessation In this study, we are looking at how the medications Varenicline and Guanfacine can be used to treat smoking.