Smoking CessationPhase 2NCT04198116
Combining Varenicline and Guanfacine for Smoking Cessation
A Phase 2 study testing Varenicline and Guanfacine ER in people with Smoking Cessation, run by Yale University at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Smoking Cessation
- What is being tested?
- Varenicline and Guanfacine ER
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 167 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Nov 2020to 30 Apr 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age 18+
- Able to read and write English
- SMOKER: 10 or more cigarettes per day for at least the past year, Carbon Monoxide (CO) > 10 ppm at intake
- Able to take oral medications and willing to adhere to medication regimen
- 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
- Motivated to quit smoking (8 or greater on the Contemplation Ladder)
Who cannot join
- 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
- 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
- Subjects who have a positive test result at intake appointment on urine drug screens conducted for illicit drugs
- Past 30 day use of psychoactive drugs excluding anxiolytics and antidepressants (however, see #10; barbiturates, benzodiazepines are exclusionary)
- 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)
- Suicidal, homicidal or evidence of current (past 6-month) severe mental illness such as schizophrenia or bipolar disorder
Show all 11Show fewer
- meeting DSM-V criteria for current (past-6 month) attention deficit hyperactivity disorder (ADHD)
- 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
- Only one member per household can participate in the study
- 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)
- Specific exclusions for the administration of varenicline not already specified: known intolerance to varenicline or taking H2blockers (e.g., Cimetidine), quinolones, or trimethoprim.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Smoking Cessation
- Being tested
- Varenicline, Guanfacine ER
- Medical subject headings
- Smoking Cessation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VareniclineDrug
Also called Chantix
Varenicline 2mg/day
Guanfacine ERDrug
Also called Intuniv
Guanfacine Extended Release (6mg/day ER)
| Study group | Role | What they receive |
|---|---|---|
| Varenicline + Guanfacine ER | Experimental | 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. Receives: Drug: Varenicline; Drug: Guanfacine ER |
| Varenicline | Active comparator | 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. Receives: Drug: Varenicline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Latency
Latency (in minutes) to time of first cigarette smoked during the 50-minute delay period.
Measured: minutes (range 0 to 50 min)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2019
- Study start1 Nov 2020
- Primary completion30 Apr 2025
- Study completion30 Apr 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Smoking CessationStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 167 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Principal investigator, Sherry McKee, Yale University
- Investigators
- Sherry McKee, PhD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04198116
- Sponsor's protocol ID
- 2000026630
- Other IDs
- R01DA047986
- Status last verified
- May 2026
- First submitted
- 3 Dec 2019
- Last updated
- 9 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combining Varenicline and Guanfacine for Smoking Cessation
- ClinicalTrials.gov ID
- NCT04198116
- Acronym / sponsor ID
- 2000026630
- Conditions
- Smoking Cessation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 167 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- 1 Nov 2020 (actual)
- Primary completion
- 30 Apr 2025 (actual)
- Study completion
- 30 Apr 2025 (actual)
- First posted
- 13 Dec 2019 (actual)
- Results
- Posted 9 Jun 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Varenicline + Guanfacine ER | Experimental | Drug: Varenicline, Drug: Guanfacine ERVarenicline (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. |
| Varenicline | Active comparator | Drug: VareniclineVarenicline (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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age 18+
- Able to read and write English
- SMOKER: 10 or more cigarettes per day for at least the past year, Carbon Monoxide (CO) > 10 ppm at intake
- Able to take oral medications and willing to adhere to medication regimen
- 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
Key exclusion criteria (11 listed)
- 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
- 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
- Subjects who have a positive test result at intake appointment on urine drug screens conducted for illicit drugs
- Past 30 day use of psychoactive drugs excluding anxiolytics and antidepressants (however, see #10; barbiturates, benzodiazepines are exclusionary)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VareniclineAlso: ChantixVarenicline 2mg/day | Drug | Varenicline, Varenicline + Guanfacine ER |
| Guanfacine ERAlso: IntunivGuanfacine Extended Release (6mg/day ER) | Drug | Varenicline + Guanfacine ER |
Primary outcome
Latency
Time frame: minutes (range 0 to 50 min)
Latency (in minutes) to time of first cigarette smoked during the 50-minute delay period.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sherry McKee, PhD principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Varenicline and Guanfacine ER in people with Smoking Cessation, run by Yale University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Jun 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Latency (time frame: minutes (range 0 to 50 min)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2026.