rTMS in Promoting Smoking Cessation and Preventing Relapse in Current Smokers

Study Overview
=================
Brief Summary
-----------------
This trial studies best dose and how well repetitive transcranial magnetic stimulation (rTMS) works in promoting smoking cessation and preventing relapse in current smokers. rTMS is a form of brain stimulation therapy that controls nerve cell activity, increases blood flow in the brain, and improves cognitive function.

Detailed Description
-----------------
PRIMARY OBJECTIVES: I. To examine the effects of stimulation duration (stimulation days) and intensity (pulses per day) on outcomes among smokers (sample size [n]=258) motivated to quit. II. To identify the most promising dosing strategy by balancing effect sizes and undesirable effects. III. To examine the effects of 16 20Hz rTMS sessions combined with intensive cognitive behavioral treatment and nicotine replacement on smoking cessation, developmental disability (DD rates), cognitive behavioral skill acquisition, and nicotine patch adherence among lung cancer (LC) patients (n=30). (Study 1 and Study 2) IV. To examine the feasibility and potential efficacy of 20Hz rTMS on the left dorsolateral prefrontal cortex (DLPFC) for concurrent smoking abstinence and reductions in alcohol use among smokers who are heavy drinkers (n=20). (Study 1 and Study 2) OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients undergo rTMS once daily (QD) or twice daily (BID) over 16 minutes for 8, 12, or 16 days. ARM II: Patients undergo sham rTMS QD or BID over 16 minutes for 8, 12, or 16 days.

Official Title
-----------------
Enhancing Relapse Prevention With rTMS: Dose-Response Parameters for Smoking Cessation

Conditions
-----------------
Cigarette Smoker, Current Every Day Smoker, Current Smoker

Intervention / Treatment
-----------------
* Other: Questionnaire Administration
* Procedure: Repetitive Transcranial Magnetic Stimulation
* Procedure: Sham Intervention


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participants will be right-handed lung cancer patients Negative urine drug screen at the baseline assessment Ability to read at the 8th grade level Passes the Transcranial Magnetic Stimulation Adult Safety and Screening Questionnaire (TASS) Participants must smoke between 5 and 25 cigarettes per day with the intent to quit smoking in the next 30 days Participant or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure Study 1: Participants will be right-handed lung cancer or head and neck cancer patients Study 1: Age 18+ Study 1: Negative urine drug screen at the baseline assessment Study 1: Ability to read at the 8th grade level Study 1: Passes the Transcranial Magnetic Stimulation Adult Safety and Screening Questionnaire (TASS) Study 1: Participants must smoke at least 4 cigarettes per day and intend to quit smoking in the next 60 days Study 1: Is a patient - with primary non-small and small cell LC or with primary non-skin squamous cell HNC Study 2: Participants will be healthy right-handed adults Study 2: Age 18-65 years old Study 2: Negative urine drug screen at the baseline assessment Study 2: Ability to read at the 8th grade level Study 2: Passes the Transcranial Magnetic Stimulation Adult Safety and Screening Questionnaire (TASS) Study 2: Participants must smoke between 5 and 25 cigarettes per day with the intent to quit smoking in the next 30 days Study 2: Meet the criteria for heavy alcohol use: > 7 drinks per week for women, > 15 drinks per week for men OR binge drinking >= 5 days in the past month. Binge drinking is defined as >= 4 drinks for women and >= 5 drinks for men, consumed within 2 hours of each other Study 2: Participant or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure Exclusion Criteria: Has a personal history of epilepsy Has a history of anticonvulsant medication use Has a personal history of head injury Has a History of aneurysm, stroke, or previous cranial neurosurgery or abnormal findings on the magnetic resonance imaging (MRI) (e.g., tumor, aneurism, etc.) Has uncontrolled major depressive disorder, bipolar disorder or a schizophrenia-spectrum disorder, or tinnitus Has any metal implants or neuro-stimulators in the head, neck, or cochlea Has a pacemaker Personal history of migraine headaches Currently taking medications that lower seizure threshold (e.g., such as tricyclic antidepressants or bupropion) Currently using medications for tobacco cessation (e.g., nicotine replacement, bupropion, varenicline, etc) Pregnant or planning to become pregnant in the next 24 weeks Current regular use of forms of tobacco other than cigarettes including e-cigarettes Participants who score above 48.3 on the Claustrophobia Questionnaire at the baseline assessment will be excluded because they are likely to be unable to undergo an magnetic resonance imaging (MRI) without distress Individuals who score >15, indicative of moderate-severe Alcohol Use Disorder, on the Alcohol Use Disorders Identification Test (AUDIT). Unwilling or unable to follow protocol requirements Any condition which in the Investigator's opinion deems the participant an unsuitable candidate to participate in the study Study 1:Has a personal history of Brain metastases Study 1: Unable to use nicotine patches Study 1: Has a Personal history of epilepsy Study 1: Has a History of anticonvulsant medication use Study 1: Has a Personal history of head injury Study 1: History of aneurysm, stroke, or previous cranial neurosurgery or abnormal findings on the MRI (e.g., tumor, aneurism, etc.) Study 1: A diagnosis of major depressive disorder, bipolar disorder or a schizophrenia-spectrum disorder, or tinnitus Study 1: Has any Metal implants or neuro-stimulators in the head, neck, or cochlea Study 1: Has a pacemaker Study 1: Personal history of Migraine headaches Study 1: Currently taking medications that lower seizure threshold (e.g., such as tricyclic antidepressants or bupropion) Study 1: Currently using bupropion or varenicline for smoking cessation Study 1: Pregnant or planning to become pregnant in the next 24 weeks Study 1: Current regular use of forms of tobacco other than cigarettes Study 1: Participants who score above 48.3 on the Claustrophobia Questionnaire at the baseline assessment will be excluded because they are likely to be unable to undergo a magnetic resonance imaging (MRI) scan without distress Study 1: Unwilling or unable to follow protocol requirements Study 1: Any condition which in the Investigator's opinion deems the participant an unsuitable candidate to participate in the study Study 2: Has a personal history of epilepsy Study 2: Has a history of anticonvulsant medication use Study 2: Has a personal history of head injury Study 2: Has a history of aneurysm, stroke, or previous cranial neurosurgery or abnormal findings on the MRI (e.g., tumor, aneurism, etc.) Study 2: Has a diagnosis of major depressive disorder, bipolar disorder or a schizophrenia-spectrum disorder, or tinnitus Study 2: Has any metal implants or neuro-stimulators in the head, neck, or cochlea Study 2: Has a pacemaker Study 2: Personal history of Migraine headaches Study 2: Currently taking medications that lower seizure threshold (e.g., such as tricyclic antidepressants or bupropion) Study 2: Currently using medications for tobacco cessation (e.g., nicotine replacement, bupropion, varenicline, etc.) Study 2: Pregnant or planning to become pregnant in the next 24 weeks Study 2: Current regular use of forms of tobacco other than cigarettes Study 2: Participants who score above 48.3 on the Claustrophobia Questionnaire at the baseline assessment will be excluded because they are likely to be unable to undergo a magnetic resonance imaging (MRI) without distress Study 2: Meet the criteria for severe alcohol use disorder (AUD) (> 6 symptoms) or have ever met Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-V) criteria for alcohol withdrawal. Heavy drinking and AUD are not mutually exclusive. Study 2: Unwilling or unable to follow protocol requirements Study 2: Any condition which in the Investigator's opinion deems the participant an unsuitable candidate to participate in the study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (rTMS)<br>Patients undergo rTMS QD or BID over 16 minutes for 8, 12, or 16 days. | Other: Questionnaire Administration<br>* Ancillary studies<br>Procedure: Repetitive Transcranial Magnetic Stimulation<br>* Undergo rTMS<br>* Other names: rTMS;|
| Sham Comparator: Arm II (sham rTMS)<br>Patients undergo sham rTMS QD or BID over 16 minutes for 8, 12, or 16 days. | Other: Questionnaire Administration<br>* Ancillary studies<br>Procedure: Sham Intervention<br>* Undergo sham rTMS<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Latency to relapse | Latency to relapse will be defined as the number of days from the quit day to relapse. Relapse will be defined as smoking for seven consecutive days. Will use Cox proportional-hazards (CPH) models to examine latency to relapse outcome. Ties in failure times will be handled using methods developed by Efron. Compliance with the CPH assumptions will be tested by coding the factors as time-dependent covariates. | Up to 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Point-prevalence abstinence rates | Will use logistic regression models to examine binary 12 and 24-week point prevalence abstinence. | At 12 and 24 weeks after quit date | 
| Delay discounting rates | Will be examined through using repeated measures Generalized Linear models. | At 12 and 24 weeks after quit date | 
| Cognitive-behavioral Therapy Skills Questionnaire | Cognitive behavioral skills will be assessed using the Cognitive-Behavioral Therapy Skills Questionnaire (CBTSQ) | Up to 24 weeks | 
| Side effects | Potential undesirable effects will be measured up to 24 weeks. | Up to 24 weeks | 
| Forever Free (FF) Booklet content Exposure | Will be measured in terms of number of content segments in each booklet. | Up to 24 weeks |