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Purpose

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

Eligibility

Eligible Ages
Between 18 Years and 65 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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

Phase
Phase 4
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Up to 90 participants will be consented, and approximately 30 participants will be randomized in a double-blind, 2-arm parallel design clinical trial comparing nicotine use abstinence rates in participants randomly assigned to: 1) varenicline + active enhanced TMS, or 2) varenicline + sham TMS.
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
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.
  • Drug: 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
  • Device: 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.
  • Behavioral: 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.
  • Drug: D-cycloserine
    Eligible participants will receive a single dose of 125 mg D-Cycloserine shortly before the start of TMS treatment.
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.
  • Drug: 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
  • 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 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.
  • Behavioral: 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.

Recruiting Locations

Massachusetts General Hospital
Boston, Massachusetts 02114
Contact:
Jodi M Gilman, PhD
617-643-7293
jgilman1@mgh.harvard.edu

More Details

Status
Recruiting
Sponsor
Massachusetts General Hospital

Study Contact

Jodi M Gilman, PhD
617-643-7293
jgilman1@mgh.harvard.edu

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 enhanced 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 varenicline 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 visit of up to 20 TMS treatments. Participants' quit date will be set following their TMS treatment day. At the TMS treatment visit, those assigned to active enhanced aTMS will receive a single dose of D-Cycloserine medication while those assigned to sham TMS will receive placebo. 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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.