[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT07698470":3,"trial-entities:NCT07698470":156,"trial-summary:NCT07698470":160},{"id":4,"nct_id":4,"org_study_id":5,"brief_title":6,"official_title":7,"overall_status":8,"completion_date":9,"status_verified_date":10,"last_update_date":11,"start_date":12,"sponsor_name":13,"lead_sponsor_class":14,"has_dmc":15,"brief_summary":16,"detailed_description":17,"conditions":18,"keywords":20,"study_type":26,"primary_purpose":27,"phases":28,"enrollment_info":30,"interventions":33,"primary_outcomes":44,"secondary_outcomes":52,"sex":53,"minimum_age":54,"maximum_age":55,"healthy_volunteers":56,"eligibility_criteria":57,"std_ages":74,"locations":76,"central_contacts":92,"overall_officials":94,"references":101,"see_also_links":155},"NCT07698470","UP-25-00525","Brain\u002FCraving Response to Smoking Cues After Oral Nicotine Pouch Use","Cue-Exposure Response Evaluation: Brain Reactivity to ONPs","RECRUITING","2027-08","2026-07","2026-07-13","2026-04-30","University of Southern California","OTHER",false,"Oral nicotine pouches (ONPs) are non-combustible nicotine products that may reduce cigarette craving and smoking cue-induced brain activity, supporting their potential as harm-reduction tools for adults who smoke cigarettes. This within-subject, repeated-measures study will evaluate the acute effects of a single 6 mg oral nicotine pouch on subjective craving and prefrontal neural responses to smoking-related cues using functional near-infrared spectroscopy (fNIRS). Participants will complete assessments before and after nicotine pouch administration following overnight nicotine abstinence to characterize changes in craving and neural cue reactivity.","This study will evaluate the acute effects of oral nicotine pouch (ONP) use on subjective cigarette craving and prefrontal neural responses to smoking-related cues among adult cigarette smokers. Although oral nicotine pouches do not involve combustion or inhalation, their effects on craving relief and neural cue reactivity following nicotine abstinence remain poorly understood. Characterizing these acute responses may improve understanding of the potential role of oral nicotine pouches as lower-risk nicotine products.\n\nThis is a single-arm, within-subject, repeated-measures study consisting of one baseline screening visit and one experimental visit. During the baseline visit, informed consent will be obtained, eligibility will be confirmed, demographic and tobacco use information will be collected, nicotine dependence will be assessed, and head circumference will be measured to determine appropriate functional near-infrared spectroscopy (fNIRS) cap sizing. Participants will also receive instructions to abstain from nicotine use for at least 12 hours before the experimental visit.\n\nAt the experimental visit, overnight nicotine abstinence will be verified before participants complete baseline assessments of subjective craving and nicotine withdrawal. Participants will then complete a standardized smoking cue reactivity task while prefrontal brain activity is recorded using functional near-infrared spectroscopy (fNIRS). Following completion of the baseline task, participants will self-administer one commercially available 6 mg oral nicotine pouch and complete a standardized 25-minute absorption period. Participants will then complete an identical post-pouch cue reactivity task with simultaneous fNIRS recording, followed by post-session assessments of craving, withdrawal, subjective product effects, and product perceptions.\n\nThe smoking cue reactivity task consists of repeated presentations of smoking-related and neutral visual cues, followed by guided imagery in which participants imagine smoking a cigarette or performing a comparable neutral behavior while holding the corresponding object. The task is administered before and after nicotine pouch administration using identical procedures to permit within-subject comparisons of neural and subjective responses.\n\nFunctional near-infrared spectroscopy is a non-invasive neuroimaging technique that measures changes in oxygenated and deoxygenated hemoglobin within cortical tissue as an indirect measure of neural activity. Brain activity will be recorded continuously throughout both cue reactivity task runs using a standardized prefrontal optode montage. Participants will be monitored throughout study procedures for discomfort, and study procedures will be discontinued if requested by the participant or if study staff determine continuation is not appropriate.",[19],"Nicotine Dependence",[21,22,23,24,25],"Oral Nicotine Pouches","Oral Nicotine Products","Smoking","Cigarettes","Harm Reduction","INTERVENTIONAL","BASIC_SCIENCE",[29],"NA",{"count":31,"type":32},45,"ESTIMATED",[34,39],{"type":14,"name":35,"description":36,"armGroupLabels":37},"Oral Nicotine Pouch","Participants will self-administer one commercially available 6 mg oral nicotine pouch following overnight nicotine abstinence. The pouch will be used for approximately 25 minutes before participants complete the post-pouch cue reactivity assessment.",[38],"Acute Oral Nicotine Pouch Administration",{"type":40,"name":41,"description":42,"armGroupLabels":43},"BEHAVIORAL","Smoking Cue Reactivity Task","Participants will complete a standardized smoking cue reactivity task before and after oral nicotine pouch administration. During each task, participants will view smoking-related and neutral images, complete guided imagination trials while holding either a cigarette or a neutral object, and undergo simultaneous functional near-infrared spectroscopy (fNIRS) to measure prefrontal brain activity.",[38],[45,49],{"measure":46,"description":47,"timeFrame":48},"Change in Prefrontal Neural Cue Reactivity to Smoking-Related Cues Measured by Functional Near-Infrared Spectroscopy (fNIRS)","Prefrontal neural responses to smoking-related and neutral cues will be assessed using functional near-infrared spectroscopy (fNIRS). The primary outcome will be the within-subject change in oxygenated (HbO) and deoxygenated (HbR) hemoglobin concentration from the pre-pouch assessment to the post-pouch assessment. Larger positive HbO responses to smoking-related cues indicate greater neural cue reactivity.","Baseline (pre-pouch) and approximately 25 minutes after administration of a 6 mg oral nicotine pouch (post-pouch) during the experimental session.",{"measure":50,"description":51,"timeFrame":48},"Change in Subjective Cigarette Craving Measured by the Questionnaire of Smoking Urges-Brief (QSU-Brief)","Subjective cigarette craving will be assessed using the Questionnaire of Smoking Urges-Brief (QSU-Brief). The QSU-Brief consists of 10 items, each rated on a 7-point Likert scale (1 = strongly disagree to 7 = strongly agree). Total scores range from 10 to 70, with higher scores indicating greater cigarette craving (worse outcome). The primary outcome will be the within-subject change in total QSU-Brief score from the pre-pouch assessment to the post-pouch assessment.",[],"ALL","21 Years","55 Years",true,{"inclusion":58,"exclusion":66,"raw_text":73},[59,60,61,62,63,64,65],"Age 21 years - 55 years","Self-reported use of cigarettes within the past 30 days","Biochemical confirmation of cigarette use:","Fagerström Test for Nicotine Dependence (FTND) score ≥5, indicating moderate to high nicotine dependence","Fluent in English","Willing to try an oral nicotine pouch","Willing to abstain from nicotine for at least 12 hours prior to each experimental session",[67,68,69,70,71,72],"Age younger than 21 years or older than 55 years","Biochemical evidence inconsistent with recent cigarette use:","Expressed intent to reduce or quit nicotine use within the next 30 days","History of medical conditions contraindicated for nicotine use (e.g., uncontrolled hypertension, recent cardiac events)","Primary use of non-cigarette products (e.g., cigars, pipe tobacco, smokeless tobacco)","Prior use of oral nicotine products in their lifetime","Inclusion Criteria:\n\n* Age 21 years - 55 years\n* Self-reported use of cigarettes within the past 30 days\n* Biochemical confirmation of cigarette use:\n\n  o Carbon monoxide (CO) breath sample ≥10 ppm\n* Fagerström Test for Nicotine Dependence (FTND) score ≥5, indicating moderate to high nicotine dependence\n* Fluent in English\n* Willing to try an oral nicotine pouch\n* Willing to abstain from nicotine for at least 12 hours prior to each experimental session\n\nExclusion Criteria:\n\n* Age younger than 21 years or older than 55 years\n* Biochemical evidence inconsistent with recent cigarette use:\n\n  o CO breath sample \\\u003C10 ppm\n* Expressed intent to reduce or quit nicotine use within the next 30 days\n* History of medical conditions contraindicated for nicotine use (e.g., uncontrolled hypertension, recent cardiac events)\n* Primary use of non-cigarette products (e.g., cigars, pipe tobacco, smokeless tobacco)\n* Prior use of oral nicotine products in their lifetime",[75],"ADULT",[77],{"facility":78,"status":8,"city":79,"state":80,"zip":81,"country":82,"contacts":83,"geoPoint":89},"University of Southern California - 3641 Watt Way (HNB B22)","Los Angeles","California","90089","United States",[84],{"name":85,"role":86,"phone":87,"email":88},"USC Nicotine and Tobacco Studies","CONTACT","213-821-0807","USCONPStudy@gmail.com",{"lat":90,"lon":91},34.05223,-118.24368,[93],{"name":85,"role":86,"phone":87,"email":88},[95,98],{"name":96,"affiliation":13,"role":97},"Natalia Peraza","PRINCIPAL_INVESTIGATOR",{"name":99,"affiliation":13,"role":100},"John Monterosso","STUDY_CHAIR",[102,106,109,112,115,118,121,124,127,130,133,136,139,142,144,147,150,153],{"pmid":103,"type":104,"citation":105},"22334123","BACKGROUND","Sofuoglu M, Herman AI, Nadim H, Jatlow P. Rapid nicotine clearance is associated with greater reward and heart rate increases from intravenous nicotine. Neuropsychopharmacology. 2012 May;37(6):1509-16. doi: 10.1038\u002Fnpp.2011.336. Epub 2012 Feb 15.",{"pmid":107,"type":104,"citation":108},"17295582","Leventhal AM, Waters AJ, Boyd S, Moolchan ET, Lerman C, Pickworth WB. Gender differences in acute tobacco withdrawal: effects on subjective, cognitive, and physiological measures. Exp Clin Psychopharmacol. 2007 Feb;15(1):21-36. doi: 10.1037\u002F1064-1297.15.1.21.",{"pmid":110,"type":104,"citation":111},"31852818","Leventhal A, Cho J, Barrington-Trimis J, Pang R, Schiff S, Kirkpatrick M. Sensory attributes of e-cigarette flavours and nicotine as mediators of interproduct differences in appeal among young adults. Tob Control. 2020 Nov;29(6):679-686. doi: 10.1136\u002Ftobaccocontrol-2019-055172. Epub 2019 Dec 18.",{"pmid":113,"type":104,"citation":114},"3954551","Hughes JR, Hatsukami D. Signs and symptoms of tobacco withdrawal. Arch Gen Psychiatry. 1986 Mar;43(3):289-94. doi: 10.1001\u002Farchpsyc.1986.01800030107013.",{"pmid":116,"type":104,"citation":117},"1932883","Heatherton TF, Kozlowski LT, Frecker RC, Fagerstrom KO. The Fagerstrom Test for Nicotine Dependence: a revision of the Fagerstrom Tolerance Questionnaire. Br J Addict. 1991 Sep;86(9):1119-27. doi: 10.1111\u002Fj.1360-0443.1991.tb01879.x.",{"pmid":119,"type":104,"citation":120},"34772504","Rest EC, Brikmanis KN, Mermelstein RJ. Preferred flavors and tobacco use patterns in adult dual users of cigarettes and ENDS. Addict Behav. 2022 Feb;125:107168. doi: 10.1016\u002Fj.addbeh.2021.107168. Epub 2021 Oct 30.",{"pmid":122,"type":104,"citation":123},"31961168","Pang RD, Goldenson NI, Kirkpatrick M, Barrington-Trimis JL, Cho J, Leventhal AM. Sex differences in the appeal of flavored e-cigarettes among young adult e-cigarette users. Psychol Addict Behav. 2020 Mar;34(2):303-307. doi: 10.1037\u002Fadb0000548. Epub 2020 Jan 20.",{"pmid":125,"type":104,"citation":126},"26687485","Kroczek AM, Haeussinger FB, Fallgatter AJ, Batra A, Ehlis AC. Prefrontal functional connectivity measured with near-infrared spectroscopy during smoking cue exposure. Addict Biol. 2017 Mar;22(2):513-522. doi: 10.1111\u002Fadb.12344. Epub 2015 Dec 21.",{"pmid":128,"type":104,"citation":129},"22708884","Shiffman S, Dunbar M, Kirchner T, Li X, Tindle H, Anderson S, Scholl S. Smoker reactivity to cues: effects on craving and on smoking behavior. J Abnorm Psychol. 2013 Feb;122(1):264-80. doi: 10.1037\u002Fa0028339. Epub 2012 Jun 18.",{"pmid":131,"type":104,"citation":132},"35923180","Keijsers M, Vega-Corredor MC, Hoermann S, Tomintz M. Cue Reactivity to Electronic Cigarettes: A Systematic Review. Subst Abuse. 2022 Jul 28;16:11782218221114971. doi: 10.1177\u002F11782218221114971. eCollection 2022.",{"pmid":134,"type":104,"citation":135},"12359667","Goldstein RZ, Volkow ND. Drug addiction and its underlying neurobiological basis: neuroimaging evidence for the involvement of the frontal cortex. Am J Psychiatry. 2002 Oct;159(10):1642-52. doi: 10.1176\u002Fappi.ajp.159.10.1642.",{"pmid":137,"type":104,"citation":138},"26806774","Ekhtiari H, Nasseri P, Yavari F, Mokri A, Monterosso J. Neuroscience of drug craving for addiction medicine: From circuits to therapies. Prog Brain Res. 2016;223:115-41. doi: 10.1016\u002Fbs.pbr.2015.10.002. Epub 2015 Dec 19.",{"pmid":140,"type":104,"citation":141},"9234050","Killen JD, Fortmann SP. Craving is associated with smoking relapse: findings from three prospective studies. Exp Clin Psychopharmacol. 1997 May;5(2):137-42. doi: 10.1037\u002F\u002F1064-1297.5.2.137.",{"type":104,"citation":143},"FDA. FDA Authorizes Marketing of 20 ZYN Nicotine Pouch Products after Extensive Scientific Review. Accessed May 14, 2025. https:\u002F\u002Fwww.fda.gov\u002Fnews-events\u002Fpress-announcements\u002Ffda-authorizes-marketing-20-zyn-nicotine-pouch-products-after-extensive-scientific-review",{"pmid":145,"type":104,"citation":146},"34034614","Azzopardi D, Liu C, Murphy J. Chemical characterization of tobacco-free \"modern\" oral nicotine pouches and their position on the toxicant and risk continuums. Drug Chem Toxicol. 2022 Sep;45(5):2246-2254. doi: 10.1080\u002F01480545.2021.1925691. Epub 2021 May 25.",{"pmid":148,"type":104,"citation":149},"36484137","Azzopardi D, Haswell LE, Frosina J, McEwan M, Gale N, Thissen J, Meichanetzidis F, Hardie G. Assessment of biomarkers of exposure and potential harm, and physiological and subjective health measures in exclusive users of nicotine pouches and current, former and never smokers. Biomarkers. 2023 Feb;28(1):118-129. doi: 10.1080\u002F1354750X.2022.2148747. Epub 2022 Dec 13.",{"pmid":151,"type":104,"citation":152},"36048111","Han DH, Cho J, Harlow AF, Tackett AP, Vogel EA, Wong M, Barrington-Trimis JL, Lerman C, Unger JB, Leventhal AM. Young adults' beliefs about modern oral nicotine products: Implications for uptake in nonvapers, dual use with e-cigarettes, and use to reduce\u002Fquit vaping. Exp Clin Psychopharmacol. 2023 Apr;31(2):455-463. doi: 10.1037\u002Fpha0000595. Epub 2022 Sep 1.",{"type":104,"citation":154},"NIDA. What is the scope of tobacco, nicotine, and e-cigarette use in the United States? . Accessed June 4, 2025. https:\u002F\u002Fnida.nih.gov\u002Fpublications\u002Fresearch-reports\u002Ftobacco-nicotine-e-cigarettes\u002Fwhat-scope-tobacco-use-its-cost-to-society",[],{"nct_id":4,"conditions":157,"biomarkers":159},[158,19],"Cigarette Smoking",[],{"nct_id":4,"found":56,"summary":161,"prompt_version":171},{"design":162,"status":163,"heading":164,"summary":165,"follow_up":166,"word_count":167,"commitments":168,"compensation":169,"drugs_mentioned":170},"This is a single-arm study, meaning all participants will receive the same intervention. It involves a small group of 45 participants.","completed","Oral Nicotine Pouch Use and Brain Response to Smoking Cues","This study is looking at how a single 6 mg oral nicotine pouch affects cigarette cravings and brain activity in people who smoke. Researchers want to see if using an oral nicotine pouch can reduce your craving for cigarettes and change how your brain reacts to smoking-related sights and thoughts. You might be able to join if you are between 21 and 55 years old, smoke cigarettes regularly, and are willing to try an oral nicotine pouch. The study will measure changes in your brain's response to smoking cues using a special brain scan (fNIRS) and your craving levels before and after using the pouch. The study is currently unclear on its recruitment status and plans to include 45 participants.","Your brain activity and craving levels will be measured at baseline and about 25 minutes after using the oral nicotine pouch during the experimental session.",120,"You will have one screening visit and one experimental visit. For the experimental visit, you will need to not use nicotine for at least 12 hours beforehand.","Not stated in the trial record.",[35],"v2"]