A Study Of Vagal Nerve Stimulation In Conjunction With NRT For Smoking Cessation

This study will evaluate the role of vagal nerve stimulation as a potential adjunct to nicotine patches to help smokers stop smoking.

• Non-invasive vagus nerve stimulator plus nicotine replacement patches (Combination product), also known as GammaCore Vagal Nerve Stimulator: VNS is a handheld, rechargeable, portable device that delivers electrical signals to the vagal nerve when positioned on the skin of the neck at the appropriate location to stimulate the vagal nerve for 2 minutes at each treatment. During these 12 weeks, participants will also use a 21 mg nicotine patch daily.
• nicotine replacement patches (Drug), also known as NRT, nicotine patches: Use of a 21 mg nicotine patch daily for up to 12 weeks

Primary outcomes

• Smoking Abstinence [week 12]: reporting smoking abstinence and having it be biochemically confirmed (CO reading of < 8 ppm)

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* 18 years of age or older at the time of consent.
* Currently smoking cigarettes on a regular basis
* Motivated to stop smoking (on a scale of 0 to 10, motivation must be 3 or above);
* Ability to participate fully in all aspects of the study.
* Have the ability to provide informed consent.
* Have no contraindicating comorbid health conditions that would interfere with study participation, as determined by the clinical investigators.

Exclusion Criteria:

* Patients with a current moderate/severe depression as assessed by a score of ≥10 on the Patient Health Questionnaire-9 (PHQ-9).
* Patients who are or have used an investigational drug within the past 30 days.
* Patients who are currently using medication(s) known to interact with varenicline.
* Patients who have clinically significant acute/chronic progressive or unstable neurologic, hepatic, renal, cardiovascular, psychological, respiratory, or metabolic disease.
* Patients with a known allergy to nicotine patches or varenicline.
* Patients with a personal history of acute pancreatitis, hypoglycemia, acute kidney injury or impairment of renal function, type 1 diabetes or diabetic ketoacidosis, and/or severe gastrointestinal disease such as gastroparesis.
* Patients with an active implantable medical device, such as a pacemaker, hearing aid implant, or any implanted electronic device.
* Patients diagnosed with narrowing of the arteries (carotid atherosclerosis)
* Patients who have had surgery to cut the vagus nerve in the neck (cervical vagotomy)
* Patients with clinically significant hypertension, hypotension, bradycardia, or tachycardia
* Patients who have a metallic device such as a stent, bone plate, or bone screw implanted at or near your neck
* Patients who are using another device at the same time (e.g., TENS Unit, muscle stimulator) or any portable electronic device (e.g., mobile phone).
* Women who are pregnant or lactating, or who are of childbearing potential and are likely to become pregnant during the medication phase but are not willing to use a reliable form of contraception, will also be excluded.

  1. Reliable forms of contraception include oral contraception, diaphragm or condom (with spermicide), injections, intrauterine devices, surgical sterilization, and abstinence. The study does not include vulnerable populations.
  2. Specifically, the study does not include fetuses, neonates, pregnant women, children (<18 years of age), prisoners, institutionalized individuals, or other vulnerable populations.

  i. All female participants of childbearing potential must have a negative pregnancy test and must agree to use approved contraception during study participation.

• Croghan IT, Hurt RT, Elrashidi MY, Milbrandt TJ, Ghosh AK, Fokken SC, Ebbert JO. Smoking Cessation in Primary Care: A Narrative Review of Evidence-Based Treatment, Emerging Technology, and Harm Reduction Approaches. J Prim Care Community Health. 2026 Jan-Dec;17:21501319261468510. doi: 10.1177/21501319261468510. Epub 2026 Jul 13. PMID 42439787

• Ivana T Croghan, PhD, Principal investigator, Mayo Clinic
• Ryan T Hurt, MD, PhD, Principal investigator, Mayo Clinic

NIH grants: R21CA302802