Clinical trial NCT05723588: Neuroimaging Correlates and Feasibility of Transcranial Magnetic Stimulation (TMS) to Improve Smoking Cessation Outcomes in Veterans With Comorbid PTSD
Official title: Neuroimaging Correlates and Feasibility of Transcranial Magnetic Stimulation (TMS) to Improve Smoking Cessation Outcomes in Veterans With Comorbid PTSD
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Tobacco Use Disorder
Keywords: Tobacco use cessation
Veterans
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2023-02-10
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Feasibility as measured by number of participants recruited
timeFrame: At consent
measure: Feasibility as measured by the percent of participants who complete the study
timeFrame: 3-month follow-up
measure: Number of participants with self-reported and bioverified abstinence from smoking
timeFrame: End of treatment, about five weeks after beginning study
measure: Number of participants with self-reported and bioverified abstinence from smoking
timeFrame: 3-month follow-up
Secondary outcomes:
measure: Average number of cigarettes smoked per day in past week
timeFrame: End of treatment, about five weeks after beginning study
measure: Average number of cigarettes smoked per day in past week
timeFrame: 3-month follow-up
measure: Self-reported withdrawal symptoms
timeFrame: End of treatment, about five weeks after beginning study
measure: Self-reported withdrawal symptoms
timeFrame: 3-month follow-up
measure: Self-report of craving based on Questionnaire of Smoking Urges
timeFrame: End of treatment, about five weeks after beginning study
measure: Self-report of craving based on Questionnaire of Smoking Urges
timeFrame: 3-month follow-up
measure: Number of participants who report relapse to smoking
timeFrame: End of treatment, about five weeks after beginning study
measure: Number of participants who report relapse to smoking
timeFrame: 3-month follow-up
measure: Functional network connectivity changes
timeFrame: End of repetitive transcranial magnetic stimulation treatment, about three weeks after beginning study
measure: Neuroimaging correlates to tobacco use
timeFrame: End of repetitive transcranial magnetic stimulation treatment, about three weeks after beginning study
measure: Self-report of craving based on Urge to Smoke Scale
timeFrame: End of treatment visit, about five weeks after beginning study
measure: Self-report of craving based on Urge to Smoke Scale
timeFrame: 3-month follow-up
measure: Self-report of craving based on Urge to Smoke Scale
timeFrame: End of treatment, about five weeks after beginning study
measure: Self-report of craving based on Urge to Smoke Scale
timeFrame: 3-month follow-up
Other outcomes:
measure: Self-report posttraumatic stress disorder (PTSD) symptoms
timeFrame: End of treatment, about five weeks after beginning study
measure: Self-report posttraumatic stress disorder (PTSD) symptoms
timeFrame: 3-month follow-up
measure: Self-reported depressive symptoms
timeFrame: End of treatment, about five weeks after beginning study
measure: Self-reported depressive symptoms
timeFrame: 3-month follow-up
measure: Severity of baseline smoking on abstinence
timeFrame: End of treatment, about five weeks after beginning study
measure: Severity of baseline smoking on abstinence
timeFrame: 3-month follow-up
Locations:
city: Durham
country: United States
facility: Durham VA Medical Center, Durham, NC
state: North Carolina
Study officials:
affiliation: Durham VA Medical Center, Durham, NC
name: Jonathan R Young, MD
role: PRINCIPAL_INVESTIGATOR
References: