Recruiting

Varenicline & aTMS

Sponsor:

Massachusetts General Hospital

Code:

NCT07145866

Conditions

Nicotine Dependence

Transcranial Magnetic Stimulation

Vaping

Smoking Cessation

Smoking (Tobacco) Addiction

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Not accepted

Interventions

Varenicline

Transcranial Magnetic Stimulation

Transcranial Magnetic Stimulation Sham

Nicotine Cessation Counseling

D-cycloserine

Study Details

Brief summary:

The goal of this clinical trial is to learn if a combination of varenicline and enhanced accelerated Transcranial Magnetic Stimulation (aTMS) works to help adults quit using nicotine products. Researchers will compare varenicline + active aTMS with a single dose of D-Clycloserine to varenicline + sham (inactive) aTMS with a placebo pill to see the effect of enhanced aTMS on reaching abstinence. The main question it aims to answer is: Does receiving active enhanced aTMS + varenicline lead to higher abstinence rates and lower nicotine craving?

Participants will be asked to:

  • Complete 2 brain MRI scans
  • Take varenicline every day for 12 weeks
  • Quit using nicotine products at the end of the second week of varenicline
  • Complete one day of up to 20 TMS treatments
  • Take a single dose of D-Cycloserine medication on the day of TMS treatment
  • Complete 12 brief, weekly follow-up visits
  • Complete a brief daily survey each day that they take the study drug

Conditions

Nicotine Dependence

Transcranial Magnetic Stimulation

Vaping

Smoking Cessation

Smoking (Tobacco) Addiction

Study ID

NCT07145866

Start date

Aug, 2026

Status verified date

Jul, 2026

Completion date

Dec, 2027

Anticipated

Primary completion date

Sep, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Age ≥ 18 and ≤65;
  • The ability to give written, informed consent;
  • Fluency in English;
  • Reported interest in quitting nicotine vaping or smoking within the next month;
  • Nicotine dependence, as defined by a score of ≥4 on the 10-question E-cigarette Dependence Inventory (ECDI) or Fagerström Test for Nicotine Dependence (FTND);
  • Smoke or vape nicotine daily for at least the past 90 days, as confirmed by self-report and timeline follow-back methods;
  • Saliva cotinine >30ng/mL;

Exclusion Criteria:

  • Pregnancy or breastfeeding;
  • Use of smoking cessation pharmacotherapy in the past month;
  • Unwilling to abstain during the study from using smoking cessation aids other than those provided by the study;
  • Prior adverse drug reaction to varenicline;
  • Contraindication to D-Cycloserine (including allergy to D-Cycloserine, significant renal impairment or known kidney disease, pregnancy)
  • Receiving or planning to receive other TMS treatments or investigational drugs during course of participation
  • Contraindications to TMS (including seizures, metallic implants, severe existing tinnitus, etc.);
  • Contraindications to MRI (including presence of a cardiac pacemaker or pacemaker wires, metallic particles in the body, vascular clips in the head or previous neurosurgery, prosthetic heart valves, claustrophobia);
  • Inpatient psychiatric hospitalization or suicide attempts in the past six months, or recent active suicidal ideation or suicidal behavior identified at enrollment or baseline visits;
  • History of seizures and/or history of TBI subtypes associated with elevated seizure risk (e.g. penetrating injury and intraparenchymal hemorrhage)
  • History of unstable neurological illness or major medical illness, such as epilepsy or renal impairment, in the past six months, unless clearly resolved;
  • In the opinion of the investigators, evidence of active problem substance use severe enough to compromise ability to safely participate;
  • In the opinion of the investigators, unable to safely participate in this study and/or provide reliable data (e.g., claustrophobia, unable to tolerate TMS or MRI procedures, etc.).

Study Design

Enrollment

30 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: Varenicline + Active Enhanced TMS

In this arm, participants will take 12 weeks of varenicline. They will also receive a single dose of 125 mg D-Cycloserine and one day of up to 20 TMS treatments, adjusted to an individualized target specific to the participant based on their brain MRI collected at the baseline imaging visit. Participants will also receive 12 brief nicotine cessation counseling sessions.

sham comparator: Varenicine + Sham TMS

In this arm, participants will receive 12 weeks of varenicline and instructions on how to take it. They will also receive one day of up to 20 TMS treatments, adjusted to an individualized target specific to the participant based on their brain MRI collected at the baseline imaging visit. However, the sham setting will deliver no magnetic field to the brain; instead, it will deliver electrical current to the scalp to mimic the feel of active treatment. Participants will also receive 12 brief nicotine cessation counseling sessions.

Interventions

Varenicline

Dosing of this FDA-approved medication will follow the below schedule, which follows the clinical standard:

0.5 mg once daily or 3 days, 0.5 mg twice daily for 4 days 1.0 mg twice daily for 11 weeks

Transcranial Magnetic Stimulation

Transcranial magnetic stimulation (TMS) is a noninvasive FDA-approved technique that is commonly used as a treatment for depression and has been approved for use in smoking cessation. In this study, TMS will be administered within FDA-approved guidelines under the supervision of a physician with experience in administering the treatment and monitoring for complications. Following an accelerated model, it will consist of up to 20 treatments in one day.

Transcranial Magnetic Stimulation Sham

Transcranial magnetic stimulation (TMS) is a noninvasive FDA-approved technique that is commonly used as a treatment for depression and has been approved for use in smoking cessation. In this study, TMS will be administered within FDA-approved guidelines under the supervision of a physician with experience in administering the treatment and monitoring for complications. Following an accelerated model, it will consist of up to 20 treatments in one day. The sham setting will deliver no magnetic field to the brain but will deliver electrical current to the scalp to mimic the feel of active treatment.

Nicotine Cessation Counseling

Each participant will receive 12 sessions of brief nicotine cessation counseling by a trained study staff member. This will be provided at the weekly follow-up visits, spread out throughout the study. This counseling, while not the main aim of the study, should help participants manage their expectations of quitting and provide support and quitting strategies throughout the process.

D-cycloserine

Eligible participants will receive a single dose of 125 mg D-Cycloserine shortly before the start of TMS treatment.

Primary outcome measure

  • Biochemically-confirmed continuous nicotine abstinence across study weeks 9-12 [ Time Frame: Week 9-Week 12 ]
  • Resting State Functional Connectivity (rsFC) [ Time Frame: Baseline, Week 12 ]
  • Change in Insula Activation to Nicotine Cues During a Cue Reactivity Task Measured by fMRI [ Time Frame: Baseline, Week 12 ]

Central Contacts and Locations

Central contacts

Jodi M Gilman, PhD

617-643-7293jgilman1@mgh.harvard.edu

Julia Jashinski, MSW

617-643-1984jjashinski@mgh.harvard.edu

Locations

Massachusetts General Hospital

Recruiting

Boston, Massachusetts, United States, 02114

Contacts

Jodi M Gilman, PhD

617-643-7293jgilman1@mgh.harvard.edu

More Information

Sponsor

Massachusetts General Hospital

Last update posted

Jul 13, 2026

Last verified

Jul, 2026

Keywords

  • Vaping
  • Smoking
  • Nicotine
  • Adults
  • Cessation
  • Varenicline
  • Transcranial Magnetic Stimulation
  • TMS
  • D-Cycloserine

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Massachusetts General Hospital on 2026-07-13.