{"protocolSection":{"identificationModule":{"nctId":"NCT00218439","orgStudyIdInfo":{"id":"0310M52790"},"secondaryIdInfos":[{"id":"K23DA017307-01","type":"NIH","link":"https://reporter.nih.gov/quickSearch/K23DA017307-01"},{"id":"DPMC","type":"OTHER","domain":"NIDA"}],"organization":{"fullName":"University of Minnesota","class":"OTHER"},"briefTitle":"Effect of Paroxetine on Smokers' Cardiovascular Response to Stress - 1","officialTitle":"Smoking, Antidepressants, and Response to Mental Stress"},"statusModule":{"statusVerifiedDate":"2019-10","overallStatus":"COMPLETED","expandedAccessInfo":{"hasExpandedAccess":false},"startDateStruct":{"date":"2005-10"},"primaryCompletionDateStruct":{"date":"2010-08","type":"ACTUAL"},"completionDateStruct":{"date":"2010-08","type":"ACTUAL"},"studyFirstSubmitDate":"2005-09-16","studyFirstSubmitQcDate":"2005-09-16","studyFirstPostDateStruct":{"date":"2005-09-22","type":"ESTIMATED"},"resultsFirstSubmitDate":"2013-10-29","resultsFirstSubmitQcDate":"2014-04-28","resultsFirstPostDateStruct":{"date":"2014-05-23","type":"ESTIMATED"},"lastUpdateSubmitDate":"2019-10-30","lastUpdatePostDateStruct":{"date":"2019-11-01","type":"ACTUAL"}},"sponsorCollaboratorsModule":{"responsibleParty":{"type":"SPONSOR"},"leadSponsor":{"name":"University of Minnesota","class":"OTHER"},"collaborators":[{"name":"National Institute on Drug Abuse (NIDA)","class":"NIH"}]},"descriptionModule":{"briefSummary":"Smokers report that they often smoke cigarettes during stressful times. The combined effect of smoking and exposure to stress leads to exaggerated increases in blood pressure, heart rate and other measures of stress response. This combination may result in greater cardiovascular harm than either smoking or stress alone. The purpose of this study is to determine the effects of paroxetine on the response to stress after smoking.","detailedDescription":"Smokers report that they often smoke cigarettes during stressful times. Smoking and stress produce similar physiological responses such as increases in heart rate, blood pressure, and adrenaline levels. The combination of smoking and stress results in greater increases in these physiological responses compared to smoking or stress alone. Such increases are thought to be harmful to cardiovascular health. Additionally, smokers with exaggerated responses to stress may be more likely to relapse following a smoking cessation attempt. The purpose of this study is to assess the effects of paroxetine, a selective serotonin reuptake inhibitor (SSRI), on the cardiovascular response to stress after smoking.\n\nParticipants in this double-blind, placebo-controlled study will receive 1 month of paroxetine and 1 month of placebo with the order of which is taken during the first month randomly assigned. Paroxetine will be administered at a daily dose of 10 mg for the first week and increased to a daily dose of 20 mg for the remainder of the study. After one month of medication, participants will abstain from smoking for one night and then undergo mental stress testing the following day. Immediately prior to the mental stress testing, participants will smoke a cigarette. Mental stressors will include speaking and math tasks. Physiological measures of stress (e.g., blood pressure, heart rate, and plasma catecholamine concentrations) and subjective measures of stress will be evaluated. Following the second month of medication, participants will again undergo the procedure for mental stress testing and evaluation."},"conditionsModule":{"conditions":["Tobacco Use Disorder"],"keywords":["Smoking"]},"designModule":{"studyType":"INTERVENTIONAL","phases":["NA"],"designInfo":{"allocation":"RANDOMIZED","interventionModel":"CROSSOVER","primaryPurpose":"TREATMENT","maskingInfo":{"masking":"DOUBLE","whoMasked":["PARTICIPANT","INVESTIGATOR"]}},"enrollmentInfo":{"count":105,"type":"ACTUAL"}},"armsInterventionsModule":{"armGroups":[{"label":"1","type":"EXPERIMENTAL","description":"Active medication for 4 weeks followed by placebo for 4 weeks","interventionNames":["Drug: Paroxetine","Drug: Placebo"]},{"label":"2","type":"EXPERIMENTAL","description":"Placebo for 4 weeks followed by active for 4 weeks","interventionNames":["Drug: Paroxetine","Drug: Placebo"]}],"interventions":[{"type":"DRUG","name":"Paroxetine","description":"10 mg for 1 week followed by 20 mg for 3 weeks","armGroupLabels":["1","2"]},{"type":"DRUG","name":"Placebo","armGroupLabels":["1","2"]}]},"outcomesModule":{"primaryOutcomes":[{"measure":"Systolic Blood Pressure Response to Stress","description":"Change in systolic blood pressure from Resting period to that observed during a speech delivered immediately after smoking a cigarette","timeFrame":"After 4 weeks of paroxetine / placebo"}],"otherOutcomes":[{"measure":"Diastolic Blood Pressure Response to Stress","description":"Change in diastolic blood pressure from Resting period to that observed during a speech delivered immediately after smoking a cigarette","timeFrame":"After 4 weeks of paroxetine / placebo"},{"measure":"Heart Rate Response to Stress","description":"Change in heart rate from Resting period to that observed during a speech delivered immediately after smoking a cigarette","timeFrame":"After 4 weeks of paroxetine / placebo"},{"measure":"Plasma Epinephrine Concentration Response to Stress","description":"Change in plasma epinephrine concentrations from Resting period to those observed during a speech delivered immediately after smoking a cigarette","timeFrame":"After 4 weeks of paroxetine / placebo"},{"measure":"Plasma Norepinephrine Concentration Response to Stress","description":"Change in plasma norepinephrine concentrations from Resting period to those observed during a speech delivered immediately after smoking a cigarette","timeFrame":"After 4 weeks of paroxetine / placebo"}]},"eligibilityModule":{"eligibilityCriteria":"Inclusion Criteria:\n\n* Smokes an average of at least 10 cigarettes per day during the year prior to enrollment\n\nExclusion Criteria:\n\n* Interested in quitting smoking within the 3 months following enrollment\n* Current unstable medical condition\n* Substance abuse within the year prior to enrollment\n* Current use of any medications (e.g., psychoactive medications, antihypertensives) that, in the opinion of the investigators, might interfere with study measures or that would be expected to interact with paroxetine (e.g., CYP2D6 substrates)\n* Smoking cessation therapy within the 3 months prior to enrollment\n* Regular use of any form of tobacco other than cigarettes\n* Significant psychiatric disorders as assessed by the PRIME-MD and verified by a clinician\n* History of hypersensitivity to any selective serotonin reuptake inhibitor\n* Pregnancy or breastfeeding","healthyVolunteers":true,"sex":"ALL","minimumAge":"18 Years","maximumAge":"65 Years","stdAges":["ADULT","OLDER_ADULT"]},"contactsLocationsModule":{"overallOfficials":[{"name":"Michael Kotlyar","affiliation":"University of Minnesota","role":"PRINCIPAL_INVESTIGATOR"}],"locations":[{"facility":"College of Pharmacy","city":"Minneapolis","state":"Minnesota","zip":"55455","country":"United States","geoPoint":{"lat":44.97997,"lon":-93.26384}}]},"referencesModule":{"references":[{"pmid":"23504241","type":"DERIVED","citation":"Kotlyar M, al'Absi M, Thuras P, Vuchetich JP, Adson DE, Nowack AL, Hatsukami DK. Effect of paroxetine on physiological response to stress and smoking. Psychosom Med. 2013 Apr;75(3):236-43. doi: 10.1097/PSY.0b013e3182898f6d. Epub 2013 Mar 15."}]}},"resultsSection":{"participantFlowModule":{"groups":[{"id":"FG000","title":"Placebo (4 Weeks) Then Paroxetine (4 Weeks)","description":"Placebo once daily in first intervention period and Paroxetine 10 mg daily for 1 week then increased to 20 mg once daily for remainder of second intervention period"},{"id":"FG001","title":"Paroxetine (4 Weeks) the Placebo (4 Weeks)","description":"Paroxetine 10 mg daily for 1 week then increased to 20 mg once daily for remainder of first intervention period, placebo once daily in second intervention period"}],"periods":[{"title":"First Intervention (4 Weeks)","milestones":[{"type":"STARTED","achievements":[{"groupId":"FG000","numSubjects":"58"},{"groupId":"FG001","numSubjects":"47"}]},{"type":"COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"40"},{"groupId":"FG001","numSubjects":"35"}]},{"type":"NOT COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"18"},{"groupId":"FG001","numSubjects":"12"}]}]},{"title":"Second Intervention (4 Weeks)","milestones":[{"type":"STARTED","achievements":[{"groupId":"FG000","numSubjects":"40"},{"groupId":"FG001","numSubjects":"35"}]},{"type":"COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"33"},{"groupId":"FG001","numSubjects":"30"}]},{"type":"NOT COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"7"},{"groupId":"FG001","numSubjects":"5"}]}]}]},"baselineCharacteristicsModule":{"populationDescription":"Includes subjects who completed both laboratory sessions (n=62). One additional subject completed both laboratory sessions but did not have usable measures in the primary outcomes (cardiovascular measures) and was excluded","groups":[{"id":"BG000","title":"Placebo First 4 Weeks, Then Paroxetine for 4 Weeks","description":"Placebo once daily in first intervention period and Paroxetine 10 mg daily for 1 week then increased to 20 mg once daily for remainder of second intervention period"},{"id":"BG001","title":"Paroxetine First 4 Weeks, Then Placebo for 4 Weeks","description":"Paroxetine 10 mg daily for 1 week then increased to 20 mg once daily for remainder of first intervention period, placebo once daily in second intervention period"},{"id":"BG002","title":"Total","description":"Total of all reporting groups"}],"denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"33"},{"groupId":"BG001","value":"29"},{"groupId":"BG002","value":"62"}]}],"measures":[{"title":"Age, Categorical","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"<=18 years","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"}]},{"title":"Between 18 and 65 years","measurements":[{"groupId":"BG000","value":"33"},{"groupId":"BG001","value":"29"},{"groupId":"BG002","value":"62"}]},{"title":">=65 years","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"}]}]}]},{"title":"Age, Continuous","paramType":"MEAN","dispersionType":"STANDARD_DEVIATION","unitOfMeasure":"years","classes":[{"categories":[{"measurements":[{"groupId":"BG000","value":"40.4","spread":"14.1"},{"groupId":"BG001","value":"40.0","spread":"11.0"},{"groupId":"BG002","value":"40.2","spread":"12.7"}]}]}]},{"title":"Sex: Female, Male","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"Female","measurements":[{"groupId":"BG000","value":"16"},{"groupId":"BG001","value":"14"},{"groupId":"BG002","value":"30"}]},{"title":"Male","measurements":[{"groupId":"BG000","value":"17"},{"groupId":"BG001","value":"15"},{"groupId":"BG002","value":"32"}]}]}]},{"title":"Region of Enrollment","paramType":"NUMBER","unitOfMeasure":"participants","classes":[{"title":"United States","categories":[{"measurements":[{"groupId":"BG000","value":"33"},{"groupId":"BG001","value":"29"},{"groupId":"BG002","value":"62"}]}]}]}]},"outcomeMeasuresModule":{"outcomeMeasures":[{"type":"PRIMARY","title":"Systolic Blood Pressure Response to Stress","description":"Change in systolic blood pressure from Resting period to that observed during a speech delivered immediately after smoking a cigarette","reportingStatus":"POSTED","paramType":"MEAN","dispersionType":"Standard Error","unitOfMeasure":"mmHg","timeFrame":"After 4 weeks of paroxetine / placebo","groups":[{"id":"OG000","title":"After 4 Weeks of Placebo","description":"Change in systolic blood pressure from Resting period to that observed during a speech delivered immediately after smoking a cigarette in those receiving 4 weeks of placebo"},{"id":"OG001","title":"After 4 Weeks of Paroxetine","description":"Change in systolic blood pressure from Resting period to that observed during a speech delivered immediately after smoking a cigarette in those receiving 4 weeks of paroxetine (1 week of 10 mg once daily followed by 3 weeks of 20 mg once daily)"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"62"},{"groupId":"OG001","value":"62"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"16.85","spread":"0.78"},{"groupId":"OG001","value":"11.71","spread":"0.78"}]}]}],"analyses":[{"groupIds":["OG000","OG001"],"nonInferiorityType":"SUPERIORITY_OR_OTHER_LEGACY","pValue":"<0.001","statisticalMethod":"Mixed Models Analysis","ciPctValue":"95"}]},{"type":"OTHER_PRE_SPECIFIED","title":"Diastolic Blood Pressure Response to Stress","description":"Change in diastolic blood pressure from Resting period to that observed during a speech delivered immediately after smoking a cigarette","reportingStatus":"POSTED","paramType":"MEAN","dispersionType":"Standard Error","unitOfMeasure":"mm Hg","timeFrame":"After 4 weeks of paroxetine / placebo","groups":[{"id":"OG000","title":"After 4 Weeks of Placebo","description":"Change in diastolic blood pressure fom Resting period to that observed during a speech delivered immediately after smoking a cigarette in those receiving 4 weeks of placebo"},{"id":"OG001","title":"After 4 Weeks of Paroxetine","description":"Change in diastolic blood pressure from Resting period to that observed during a speech delivered immediately after smoking a cigarette in those receiving 4 weeks of paroxetine (1 week of 10 mg once daily followed by 3 weeks of 20 mg once daily)"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"62"},{"groupId":"OG001","value":"62"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"9.78","spread":"0.49"},{"groupId":"OG001","value":"8.07","spread":"0.5"}]}]}],"analyses":[{"groupIds":["OG000","OG001"],"nonInferiorityType":"SUPERIORITY_OR_OTHER_LEGACY","pValue":"0.006","statisticalMethod":"Mixed Models Analysis"}]},{"type":"OTHER_PRE_SPECIFIED","title":"Heart Rate Response to Stress","description":"Change in heart rate from Resting period to that observed during a speech delivered immediately after smoking a cigarette","reportingStatus":"POSTED","paramType":"MEAN","dispersionType":"Standard Error","unitOfMeasure":"beats/minute","timeFrame":"After 4 weeks of paroxetine / placebo","groups":[{"id":"OG000","title":"After 4 Weeks of Placebo","description":"Change in heart rate from Resting period to that observed during a speech delivered immediately after smoking a cigarette in those receiving 4 weeks of placebo"},{"id":"OG001","title":"After 4 Weeks of Paroxetine","description":"Change in heart rate from Resting period to that observed during a speech delivered immediately after smoking a cigarette in those receiving 4 weeks of paroxetine (1 week of 10 mg once daily followed by 3 weeks of 20 mg once daily)"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"62"},{"groupId":"OG001","value":"62"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"20.39","spread":"0.56"},{"groupId":"OG001","value":"20.02","spread":"0.56"}]}]}],"analyses":[{"groupIds":["OG000","OG001"],"nonInferiorityType":"SUPERIORITY_OR_OTHER_LEGACY","pValue":"0.56","statisticalMethod":"Mixed Models Analysis"}]},{"type":"OTHER_PRE_SPECIFIED","title":"Plasma Epinephrine Concentration Response to Stress","description":"Change in plasma epinephrine concentrations from Resting period to those observed during a speech delivered immediately after smoking a cigarette","reportingStatus":"POSTED","paramType":"MEAN","dispersionType":"Standard Error","unitOfMeasure":"pg / ml","timeFrame":"After 4 weeks of paroxetine / placebo","groups":[{"id":"OG000","title":"After 4 Weeks of Placebo","description":"Change in plasma epinephrine concentrations from Resting period to those observed during a speech delivered immediately after smoking a cigarette in those receiving 4 weeks of placebo"},{"id":"OG001","title":"After 4 Weeks of Paroxetine","description":"Change in plasma epinephrine concentrations from Resting period to those observed during a speech delivered immediately after smoking a cigarette in those receiving 4 weeks of paroxetine (1 week of 10 mg once daily followed by 3 weeks of 20 mg once daily)"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"62"},{"groupId":"OG001","value":"62"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"40.98","spread":"3.42"},{"groupId":"OG001","value":"34.94","spread":"3.48"}]}]}],"analyses":[{"groupIds":["OG000","OG001"],"nonInferiorityType":"SUPERIORITY_OR_OTHER_LEGACY","pValue":"0.33","statisticalMethod":"Mixed Models Analysis"}]},{"type":"OTHER_PRE_SPECIFIED","title":"Plasma Norepinephrine Concentration Response to Stress","description":"Change in plasma norepinephrine concentrations from Resting period to those observed during a speech delivered immediately after smoking a cigarette","reportingStatus":"POSTED","paramType":"MEAN","dispersionType":"Standard Error","unitOfMeasure":"pg / ml","timeFrame":"After 4 weeks of paroxetine / placebo","groups":[{"id":"OG000","title":"After 4 Weeks of Placebo","description":"Change in plasma norepinephrine concentrations from Resting period to those observed during a speech delivered immediately after smoking a cigarette in those receiving 4 weeks of placebo"},{"id":"OG001","title":"After 4 Weeks of Paroxetine","description":"Change in plasma norepinephrine concentrations from Resting period to those observed during a speech delivered immediately after smoking a cigarette in those receiving 4 weeks of paroxetine (1 week of 10 mg once daily followed by 3 weeks of 20 mg once daily)"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"62"},{"groupId":"OG001","value":"62"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"72.31","spread":"18.32"},{"groupId":"OG001","value":"63.37","spread":"18.32"}]}]}],"analyses":[{"groupIds":["OG000","OG001"],"nonInferiorityType":"SUPERIORITY_OR_OTHER_LEGACY","pValue":"0.82","statisticalMethod":"Mixed Models Analysis"}]}]},"adverseEventsModule":{"frequencyThreshold":"5","timeFrame":"Adverse events data collected during treatment (i.e. 4 weeks of paroxetine or 4 weeks of placebo)","description":"Subjects were asked at each visit an open ended question if they've experienced any side effects","eventGroups":[{"id":"EG000","title":"During 4 Weeks of Placebo","description":"Participants receive placebo daily for 4 weeks","seriousNumAffected":0,"seriousNumAtRisk":62,"otherNumAffected":34,"otherNumAtRisk":62},{"id":"EG001","title":"During 4 Weeks of Paroxetine","description":"Participants received paroxetine 10 mg once daily for 1 week followed by 20 mg once daily for 3 weeks","seriousNumAffected":0,"seriousNumAtRisk":62,"otherNumAffected":35,"otherNumAtRisk":62}],"otherEvents":[{"term":"Dizziness","organSystem":"General disorders","assessmentType":"NON_SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numAffected":1,"numAtRisk":62},{"groupId":"EG001","numAffected":6,"numAtRisk":62}]},{"term":"Gastrointenstinal symptoms","organSystem":"Gastrointestinal disorders","assessmentType":"NON_SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numAffected":7,"numAtRisk":62},{"groupId":"EG001","numAffected":13,"numAtRisk":62}]},{"term":"drowsiness","organSystem":"General disorders","assessmentType":"NON_SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numAffected":10,"numAtRisk":62},{"groupId":"EG001","numAffected":16,"numAtRisk":62}]},{"term":"sexual side effects","organSystem":"Reproductive system and breast disorders","assessmentType":"NON_SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numAffected":1,"numAtRisk":62},{"groupId":"EG001","numAffected":5,"numAtRisk":62}]},{"term":"insomnia","organSystem":"General disorders","assessmentType":"NON_SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numAffected":3,"numAtRisk":62},{"groupId":"EG001","numAffected":4,"numAtRisk":62}]},{"term":"dry mouth / taste changes","organSystem":"General disorders","assessmentType":"NON_SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numAffected":1,"numAtRisk":62},{"groupId":"EG001","numAffected":6,"numAtRisk":62}]},{"term":"headache","organSystem":"General disorders","assessmentType":"NON_SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numAffected":1,"numAtRisk":62},{"groupId":"EG001","numAffected":4,"numAtRisk":62}]},{"term":"change in appetite","organSystem":"Gastrointestinal disorders","assessmentType":"NON_SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numAffected":5,"numAtRisk":62},{"groupId":"EG001","numAffected":3,"numAtRisk":62}]},{"term":"unusual dreams","organSystem":"General disorders","assessmentType":"NON_SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numAffected":5,"numAtRisk":62},{"groupId":"EG001","numAffected":0,"numAtRisk":62}]},{"term":"anxiety / irritability","organSystem":"General disorders","assessmentType":"NON_SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numAffected":8,"numAtRisk":62},{"groupId":"EG001","numAffected":3,"numAtRisk":62}]}]},"moreInfoModule":{"certainAgreement":{"piSponsorEmployee":false,"restrictiveAgreement":false},"pointOfContact":{"title":"Dr. Michael Kotlyar","organization":"University of Minnesota College of Pharmacy","email":"kotly001@umn.edu","phone":"612-625-1160"}}},"derivedSection":{"miscInfoModule":{"versionHolder":"2026-10-13"},"conditionBrowseModule":{"meshes":[{"id":"D014029","term":"Tobacco Use Disorder"},{"id":"D012907","term":"Smoking"}],"ancestors":[{"id":"D019966","term":"Substance-Related Disorders"},{"id":"D064419","term":"Chemically-Induced Disorders"},{"id":"D001523","term":"Mental Disorders"},{"id":"D001519","term":"Behavior"}]},"interventionBrowseModule":{"meshes":[{"id":"D017374","term":"Paroxetine"}],"ancestors":[{"id":"D010880","term":"Piperidines"},{"id":"D006573","term":"Heterocyclic Compounds, 1-Ring"},{"id":"D006571","term":"Heterocyclic Compounds"}]}},"hasResults":true}