Varenicline and Accelerated Transcranial Magnetic Stimulation (TMS) for Quitting Nicotine Use (Pilot Study)

NCT ID: NCT07145866

Last Updated: 2026-01-16

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-03-15
• Study Completion Date: 2027-12-01

Brief Summary

The goal of this clinical trial is to learn if a combination of varenicline and accelerated Transcranial Magnetic Stimulation (aTMS) works to help adults quit using nicotine products. Researchers will compare varenicline + active aTMS to varenicline + sham (inactive) aTMS to see the effect of aTMS on reaching abstinence. The main question it aims to answer is: Does receiving active 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 5 consecutive days (Monday-Friday, uninterrupted) of TMS treatments
• Complete 12 brief, weekly follow-up visits
• Complete a brief daily survey each day that they take the study drug

Detailed Description

This is a 12-week randomized parallel design, double-blind, 2-arm clinical trial consisting of a combination of circuit-targeted TMS and varenicline in 30 adults aged 18-65 with nicotine use disorder who would like to reduce or stop nicotine use.

Eligible participants will complete a baseline assessment of questionnaires and laboratory assessments. They will be randomized to receive varenicline and either active or sham TMS. Participants will be randomized at their baseline scan visit, during which they will undergo urinalysis, an fMRI scan, and a task and questionnaire battery. At this visit, participants will receive the study medication and will be instructed to take it for 12 weeks titrated to 1mg twice daily over seven days.

Shortly after, participants will complete a TMS treatment preparation visit during which the treatment target is located and stimulation intensity of the TMS is determined. This target is used in the subsequent TMS Treatment Week consisting of 5 consecutive days of 5 TMS treatments per day. Participants' quit date will be set for the Saturday following their TMS treatments. The week after completing their TMS treatments, they will return for a second imaging visit identical to the baseline scan.

Each week of the varenicline treatment period, participants will complete weekly follow-ups with study staff, either virtually or in-person, to determine nicotine use and complete questionnaires regarding their substance use in the past week, depression, and anxiety. Six of these visits will include brief sessions of nicotine use cessation counseling with a trained study staff member.

Conditions

Nicotine Dependence; Transcranial Magnetic Stimulation; Vaping; Smoking Cessation; Smoking (Tobacco) Addiction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Varenicline + Active TMS

In this arm, participants will take 12 weeks of varenicline. They will also receive 5 consecutive days of 5 hourly 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 6 brief nicotine cessation counseling sessions.

Group Type: ACTIVE_COMPARATOR

varenicline

Intervention Type: DRUG

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

Intervention Type: DEVICE

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 5 hourly treatments for 5 consecutive days.

Nicotine Cessation Counseling

Intervention Type: BEHAVIORAL

Each participant will receive 6 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.

Varenicine + Sham TMS

In this arm, participants will receive 12 weeks of varenicline and instructions on how to take it. They will also receive 5 consecutive days of 5 hourly 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 6 brief nicotine cessation counseling sessions.

Group Type: SHAM_COMPARATOR

varenicline

Intervention Type: DRUG

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 Sham

Intervention Type: DEVICE

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 5 hourly treatments for 5 consecutive days. 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

Intervention Type: BEHAVIORAL

Each participant will receive 6 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.

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

Intervention Type: DRUG

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 5 hourly treatments for 5 consecutive days.

Intervention Type: DEVICE

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 5 hourly treatments for 5 consecutive days. 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.

Intervention Type: DEVICE

Nicotine Cessation Counseling

Each participant will receive 6 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.

Intervention Type: BEHAVIORAL

Eligibility Criteria

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;
• 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.).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Brigham and Women's Hospital

OTHER

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Jodi Gilman

Associate Professor, Harvard Medical School; Director of Neuroscience, Center for Addiction Medicine, Massachusetts General Hospital

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jodi M Gilman, PhD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

Countries

United States

Central Contacts

Jodi M Gilman, PhD

Role: CONTACT

jgilman1@mgh.harvard.edu

617-643-7293

Julia Jashinski, MSW

Role: CONTACT

jjashinski@mgh.harvard.edu

617-643-1984

Facility Contacts

Jodi M Gilman, PhD

Role: primary

jgilman1@mgh.harvard.edu

617-643-7293

Other Identifiers

2025P001964

Identifier Type: -

Identifier Source: org_study_id