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

140 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Varenicline for smoking cessation?

Varenicline has been shown to be effective in helping people quit smoking, with studies indicating that it significantly increases the chances of long-term abstinence compared to a placebo or another smoking cessation drug, bupropion. It works by reducing withdrawal symptoms and the urge to smoke, making it a valuable option for those looking to quit smoking. ^{1 2 3 4 5}

Is the combination of Varenicline and Guanfacine safe for smoking cessation?

Varenicline, used for smoking cessation, has been generally well tolerated but has been associated with some psychiatric side effects like depression and changes in behavior. It's important to discuss potential risks and benefits with a healthcare provider. ^{1 6 7 8 9}

What makes the drug combination of Varenicline and Guanfacine unique for smoking cessation?

The combination of Varenicline and Guanfacine for smoking cessation is unique because Varenicline is a partial agonist that targets specific nicotine receptors to reduce cravings and withdrawal symptoms, while Guanfacine, typically used for ADHD and hypertension, may help manage stress and impulse control, potentially enhancing the effectiveness of smoking cessation efforts. ^{1 6 9 10 11}

What is the purpose of this trial?

The novel design of this study combines a laboratory paradigm to evaluate stress-induced smoking behavior and smoking-related reinforcement, followed by a 12-week treatment phase to evaluate clinical outcomes.

Research Team

Sherry McKee, PhD

Principal Investigator

Yale University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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 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]

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 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 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 (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]

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]

References

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

Varenicline: a review of its use as an aid to smoking cessation therapy. [2018]

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

Varenicline: a selective alpha4beta2 nicotinic acetylcholine receptor partial agonist approved for smoking cessation. [2017]

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

Varenicline dose dependently enhances responding for nonpharmacological reinforcers and attenuates the reinforcement-enhancing effects of nicotine. [2021]

4. England 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. [2021]

5. United States 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. [2023]

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

Treatment of nicotine dependence with Chantix (varenicline). [2015]

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

Effectiveness of varenicline as an aid to smoking cessation: results of an inter-European observational study. [2015]

8. Japan pubmed.ncbi.nlm.nih.gov

[Sustainable efficacy of oral varenicline for smoking cessation]. [2015]

9. New Zealand 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. [2021]

10. Belgium pubmed.ncbi.nlm.nih.gov

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

11. United States 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. [2022]