Neuroimaging Correlates and Feasibility of Transcranial Magnetic Stimulation (TMS) to Improve Smoking Cessation Outcomes in Veterans With Comorbid PTSD

NCT ID: NCT05723588

Last Updated: 2025-03-14

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-10-31
• Study Completion Date: 2027-11-01

Brief Summary

Tobacco use is the number one preventable cause of the death in the United States, and is high among US Veterans, and those who have experienced trauma are more likely to smoke. Despite the efficacy of current evidence-based treatments for smoking cessation, there is a critical need for alternative treatments. This project seeks to evaluate the feasibility and effectiveness of a smoking cessation treatment for Veterans with posttraumatic stress disorder (PTSD) who smoke. The treatment combines smoking cessation counseling, nicotine replacement therapy (e.g., nicotine gum), and repetitive transcranial magnetic stimulation (rTMS). rTMS is a noninvasive brain stimulation treatment that has been cleared by the Food and Drug Administration for smoking cessation in adults.

Detailed Description

Tobacco use remains the number one preventable cause of death in the United States. Unfortunately, individuals with mental health conditions are disproportionately affected. Tobacco use is also high among US Veterans, and those who have experienced trauma are even more likely to smoke. Successful quitting is especially difficult for individuals who develop posttraumatic stress disorder (PTSD). Despite the efficacy of current evidence-based pharmacotherapies and psychotherapies for smoking cessation, alternative treatments are critically needed. Neuroimaging techniques such as resting-state functional magnetic resonance imaging (rs-fMRI) have provided insight into the neurocircuitry of tobacco use disorder (TUD) and successful quit attempts. Interventions that modulate the neural systems underlying TUD, such as repetitive transcranial magnetic stimulation (rTMS), may be critical to improving clinical outcomes. Indeed, the US Food and Drug Administration (FDA) recently cleared a form of rTMS as a short-term smoking cessation treatment in adults. However, most clinical trials on rTMS for smoking cessation have been conducted in civilian samples and have excluded individuals with psychiatric conditions. To improve smoking cessation treatment options for Veterans with PTSD, it is critical to evaluate novel brain stimulation methods such as rTMS in this vulnerable population. Furthermore, the development of neuroscience-informed techniques to enhance rTMS such as neuronavigation based on rs-fMRI is critical to individualizing rTMS for smoking cessation and understanding mechanisms of action. The application of neuroimaging to develop personalized rTMS targets to precisely modulate targeted underlying neurocircuitry has been successfully applied to the treatment of major depressive disorder (MDD). Similar methodology has been demonstrated successfully for smoking cessation by the candidate's mentors, but this work was completed in a sample of civilian participants making a quit attempt who did not have psychiatric illness. To fill these knowledge gaps, the proposed research aims to develop feasibility data for the therapeutic application individualized neuronavigated rTMS for Veterans with PTSD attempting to quit smoking. Using a feasibility randomized controlled trial (RCT) design, eligible Veterans with PTSD (n=50) seeking smoking cessation will receive rs-fMRI before and after a 5-day course of neuronavigated rTMS the week prior to their quit date, in conjunction with nicotine replacement therapy (NRT) and cognitive behavioral therapy (CBT). The scientific aims of the study are to evaluate feasibility of treatment delivery procedures, develop preliminary effect size estimates, and demonstrate target engagement of the intervention within neural networks critical to TUD.

Conditions

Tobacco Use Disorder

Study Design

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

Study Groups

active rTMS

Participants assigned to this group will receive active repetitive transcranial magnetic stimulation (rTMS) as part of their smoking cessation treatment.

Group Type: EXPERIMENTAL

active repetitive transcranial magnetic stimulation

Intervention Type: DEVICE

Active rTMS is a non-invasive brain stimulation intervention that is FDA cleared as a treatment for smoking cessation in adults.

cognitive behavioral therapy for smoking cessation

Intervention Type: BEHAVIORAL

All participants will receive five sessions of cognitive behavioral therapy (CBT) for smoking cessation.

nicotine replacement therapy

Intervention Type: DRUG

All participants will receive nicotine replacement therapy in for the form of 21 mg, 14 mg, and/or 7 mg nicotine patches (based on smoking quantity) and a "rescue" method such as nicotine lozenge or nicotine gum.

sham rTMS

Participants assigned to this group will receive sham repetitive transcranial magnetic stimulation (rTMS) as part of their smoking cessation treatment.

Group Type: SHAM_COMPARATOR

sham repetitive transcranial magnetic stimulation

Intervention Type: DEVICE

Sham rTMS involves no brain stimulation, but appears to the participant and provider to be active rTMS.

cognitive behavioral therapy for smoking cessation

Intervention Type: BEHAVIORAL

All participants will receive five sessions of cognitive behavioral therapy (CBT) for smoking cessation.

nicotine replacement therapy

Intervention Type: DRUG

All participants will receive nicotine replacement therapy in for the form of 21 mg, 14 mg, and/or 7 mg nicotine patches (based on smoking quantity) and a "rescue" method such as nicotine lozenge or nicotine gum.

Interventions

active repetitive transcranial magnetic stimulation

Active rTMS is a non-invasive brain stimulation intervention that is FDA cleared as a treatment for smoking cessation in adults.

Intervention Type: DEVICE

sham repetitive transcranial magnetic stimulation

Sham rTMS involves no brain stimulation, but appears to the participant and provider to be active rTMS.

Intervention Type: DEVICE

cognitive behavioral therapy for smoking cessation

All participants will receive five sessions of cognitive behavioral therapy (CBT) for smoking cessation.

Intervention Type: BEHAVIORAL

nicotine replacement therapy

All participants will receive nicotine replacement therapy in for the form of 21 mg, 14 mg, and/or 7 mg nicotine patches (based on smoking quantity) and a "rescue" method such as nicotine lozenge or nicotine gum.

Intervention Type: DRUG

Other Intervention Names

active rTMS; sham rTMS; CBT; NRT, nicotine patch, nicotine gum, nicotine lozenges

Eligibility Criteria

Inclusion Criteria

• Is a US Veteran
• Meets DSM-5 criteria for tobacco use disorder
• Is between the ages of 18 and 75
• Smokes an average of 10 cigarettes per day for the past 6 months, with carbon monoxide (CO) level > 6 ppm
• Is willing to attempt smoking cessation
• Meets DSM-5 criteria for current PTSD diagnosis
• Speaks, reads and writes English
• Is willing to sign a Duke consent for those portions of the study that occur at Duke
• Has been stable on psychotropic medications for at least three months

Exclusion Criteria

• Has had a substance use disorder other than tobacco in the preceding 3 months
• Has a history of myocardial infarction in the past 6 months or has another contraindication to NRT
• Has a contraindication to TMS or MRI

• Personal or family history of a seizures or epilepsy
• History of neurological condition that increases the risk of seizures including stroke or transient ischemic attack, cerebral aneurysm, or severe traumatic brain injury from a penetrating head injury, loss of consciousness > 20 minutes at time of traumatic injury, requiring an anticonvulsant medication for seizures, and/or found to have encephalomalacia on baseline MRI
• Structural brain lesion, or prior brain surgery
• Ferromagnetic metal in head (including shrapnel)
• Implanted devices that may be affected by MRI or TMS (pacemaker, medication pump, cochlear implant, implanted deep brain stimulator)
• Is pregnant (to be determined at Duke)
• Is unable to complete study procedures
• Is currently prescribed bupropion and/or varenicline
• Uses other forms of nicotine such as cigars, pipes, chewing tobacco, or vaping
• Is unable to provide informed consent due to a major neurocognitive disorder or other reason
• Meets criteria for a primary psychotic disorder or current manic episode
• Is currently imprisoned or psychiatrically hospitalized
• Has previously received rTMS

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

VA Office of Research and Development

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jonathan R Young, MD

Role: PRINCIPAL_INVESTIGATOR

Durham VA Medical Center, Durham, NC

Locations

Durham VA Medical Center, Durham, NC

Durham, North Carolina, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Jonathan R Young, MD

Role: CONTACT

jonathan.young14@va.gov

(919) 286-0411

Angela C Kirby, MS

Role: CONTACT

angela.kirby@va.gov

(919) 286-0411 ext. 7456

Facility Contacts

Virginia J Rhodes

Role: primary

Virginia.Rhodes@va.gov

919-286-0411 ext. 177632

Other Identifiers

1625460

Identifier Type: OTHER

Identifier Source: secondary_id

CX002610

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

NURA-001-22S

Identifier Type: -

Identifier Source: org_study_id