Combining Varenicline and Guanfacine for Smoking Cessation

May 13, 2026 updated by: Sherry McKee, Yale University
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Using a double-blind, this Phase 2 study will randomize 140 smokers to a parallel group design (varenicline + guanfacine vs. varenicline alone). Following titration to steady state levels, the investigators will evaluate sex differences in medication effects on stress-induced smoking behavior and smoking-related reinforcement in the laboratory, and on abstinence outcomes during a subsequent 12-week treatment period.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
167

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Connecticut
      • New Haven, Connecticut, United States, 06519
        • Yale University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  1. Age 18+
  2. Able to read and write English
  3. SMOKER: 10 or more cigarettes per day for at least the past year, Carbon Monoxide (CO) > 10 ppm at intake
  4. Able to take oral medications and willing to adhere to medication regimen
  5. Provide evidence of a stable living residence in the last 2 months prior to randomization, have reasonable transportation arrangements to the study site, have no plans to move within the next 3 months, and have no unresolved legal problems
  6. Motivated to quit smoking (8 or greater on the Contemplation Ladder)

Exclusion Criteria:

  1. Subjects with any significant current medical conditions (neurological, cardiovascular [including hypertension or hypotension: sitting BP >160/100 or <90/60mmHg at baseline screening], endocrine, thyroid, renal, liver), seizures, delirium or hallucinations, or other unstable medical conditions
  2. Current Diagnostic and Statistical Manual of Mental Disorders (DSM-V) alcohol or substances use disorders, other than mild alcohol use disorder or tobacco use disorder
  3. Subjects who have a positive test result at intake appointment on urine drug screens conducted for illicit drugs
  4. Past 30 day use of psychoactive drugs excluding anxiolytics and antidepressants (however, see #10; barbiturates, benzodiazepines are exclusionary)
  5. Women who are pregnant or nursing, or fail to use one of the following methods of birth control unless she or partner is surgically sterile or she is postmenopausal (hormone contraceptives [oral, implant, injection, patch, or ring], contraceptive sponge, double barrier [diaphragm or condom plus spermicide], or IUD)
  6. Suicidal, homicidal or evidence of current (past 6-month) severe mental illness such as schizophrenia or bipolar disorder
  7. meeting DSM-V criteria for current (past-6 month) attention deficit hyperactivity disorder (ADHD)
  8. Individuals who are currently taking medications known to be effective for smoking cessation (e.g., FDA smoking cessation medications, nortriptyline, clonidine) or are regular users of e-cigarettes or other tobacco projects (pipe, cigar, smokeless tobacco) in the past 30 days
  9. Only one member per household can participate in the study
  10. Specific exclusions for administration of guanfacine not already specified: EKG evidence at baseline screening of any clinically significant conduction abnormalities or arrhythmias; known intolerance for guanfacine or any alpha blocker; history of fainting, syncopal attacks, heart failure or myocardial infarction, or impaired liver (aspartate aminotransferase [AST], alanine aminotransferase [ALT] > 3x normal) or renal function (estimated creatinine clearance <60 cc/min); treatment with any antihypertensive drug or any alpha-blocker; use of any central nervous system (CNS) depressant (e.g., phenothiazines, barbiturates, benzodiazepines)
  11. Specific exclusions for the administration of varenicline not already specified: known intolerance to varenicline or taking H2blockers (e.g., Cimetidine), quinolones, or trimethoprim.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Varenicline + Guanfacine ER
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.
Drug: Varenicline
Varenicline 2mg/day
Other Names:
  • Chantix
Drug: Guanfacine ER
Guanfacine Extended Release (6mg/day ER)
Other Names:
  • Intuniv
Active Comparator: Varenicline
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.
Drug: Varenicline
Varenicline 2mg/day
Other Names:
  • Chantix

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Latency
Time Frame: minutes (range 0 to 50 min)
Latency (in minutes) to time of first cigarette smoked during the 50-minute delay period.
minutes (range 0 to 50 min)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Yale University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute on Drug Abuse (NIDA)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Sherry McKee, PhD, Yale University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 30, 2025

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 30, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 3, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 11, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 13, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 9, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 13, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2000026630
  • R01DA047986 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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