140 Participants Needed

Varenicline + Guanfacine for Smoking Cessation

ML
SC
Overseen BySabrina Coppola
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

Trial Summary

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.

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.12345

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.16789

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.1691011

Research Team

SM

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.
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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.
See 8 more

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 OverviewThe 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
2Treatment groups
Experimental Treatment
Active Control
Group I: Varenicline + Guanfacine ERExperimental Treatment2 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: VareniclineActive Control1 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)
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Approved in European Union as Intuniv for:
  • Attention Deficit Hyperactivity Disorder (ADHD)
🇪🇺
Approved in European Union as Paxneury for:
  • Attention Deficit Hyperactivity Disorder (ADHD)

Find a Clinic Near You

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.
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.
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.
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]

References

Varenicline: a review of its use as an aid to smoking cessation therapy. [2018]
Varenicline: a selective alpha4beta2 nicotinic acetylcholine receptor partial agonist approved for smoking cessation. [2017]
Varenicline dose dependently enhances responding for nonpharmacological reinforcers and attenuates the reinforcement-enhancing effects of nicotine. [2021]
Effectiveness of Varenicline Versus Combination Nicotine Replacement Therapy for Smoking Cessation: One-Year Outcomes in a Smoking Cessation Clinic in Taiwan. [2021]
Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial. [2023]
Treatment of nicotine dependence with Chantix (varenicline). [2015]
Effectiveness of varenicline as an aid to smoking cessation: results of an inter-European observational study. [2015]
[Sustainable efficacy of oral varenicline for smoking cessation]. [2015]
Safety and drug utilization profile of varenicline as used in general practice in England: interim results from a prescription-event monitoring study. [2021]
[Drug of the month. Varenicline (Champix)]. [2015]
11.United Statespubmed.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]