{ "FullStudy":{ "Rank":218186, "Study":{ "ProtocolSection":{ "IdentificationModule":{ "NCTId":"NCT01511614", "OrgStudyIdInfo":{ "OrgStudyId":"999912474" }, "SecondaryIdInfoList":{ "SecondaryIdInfo":[ { "SecondaryId":"12-DA-N474" } ] }, "Organization":{ "OrgFullName":"National Institutes of Health Clinical Center (CC)", "OrgClass":"NIH" }, "BriefTitle":"Nicotine Withdrawal Symptoms and Smoking Relapse", "OfficialTitle":"Identifying Neurobiological Mechanisms That Underlie Acute Nicotine Withdrawal and Drive Early Relapse in Smokers" }, "StatusModule":{ "StatusVerifiedDate":"March 6, 2020", "OverallStatus":"Recruiting", "ExpandedAccessInfo":{ "HasExpandedAccess":"No" }, "StartDateStruct":{ "StartDate":"May 20, 2013", "StartDateType":"Actual" }, "PrimaryCompletionDateStruct":{ "PrimaryCompletionDate":"December 31, 2020", "PrimaryCompletionDateType":"Anticipated" }, "CompletionDateStruct":{ "CompletionDate":"December 31, 2022", "CompletionDateType":"Anticipated" }, "StudyFirstSubmitDate":"January 13, 2012", "StudyFirstSubmitQCDate":"January 13, 2012", "StudyFirstPostDateStruct":{ "StudyFirstPostDate":"January 18, 2012", "StudyFirstPostDateType":"Estimate" }, "LastUpdateSubmitDate":"March 14, 2020", "LastUpdatePostDateStruct":{ "LastUpdatePostDate":"March 17, 2020", "LastUpdatePostDateType":"Actual" } }, "SponsorCollaboratorsModule":{ "ResponsibleParty":{ "ResponsiblePartyType":"Sponsor" }, "LeadSponsor":{ "LeadSponsorName":"National Institute on Drug Abuse (NIDA)", "LeadSponsorClass":"NIH" } }, "OversightModule":{ "IsFDARegulatedDrug":"No", "IsFDARegulatedDevice":"No" }, "DescriptionModule":{ "BriefSummary":"Background:\n\n- Smoking is thought to cause changes in the brain that lead to addiction and craving. Smokers who try to quit experience nicotine withdrawal symptoms that include irritability, anxiety, and difficulty concentrating. These symptoms make it difficult for people to stop smoking. Many people say that they continue smoking to help relieve these symptoms, often within the first week after trying to quit. Researchers want to study what is happening in the brain to cause these symptoms, which may help identify new ways to successfully quit smoking.\n\nObjectives:\n\n- To study nicotine withdrawal symptoms and brain function in smokers who stop smoking for 36 hours.\n\nEligibility:\n\n- Individuals between 18 and 65 years of age who smoke at least 10 cigarettes per day. Participants must be able to stop smoking for 36 hours on two occasions.\n\nDesign:\n\nPhase 1\n\nThis study will involve three visits to the National Institute on Drug Abuse.\nNOT be able to smoke for 36 hours before the two imaging visits.\nWear a nicotine skin patch or a placebo (fake) patch during your 36 hour smoking abstinence period and study visits.\nHave your blood drawn to test for levels of stress-related hormones.\nComplete multiple MRI scanning sessions that last about 1.5 to 2 hours each.\nUndergo EEG (brain waves) recording.\nAnswer questionnaires about how you think and feel.\nComplete various tasks and procedures inside and outside of the MRI scanner.\n\nPhase 2\n\nThis study will involve thirteen visits to the National Institute on Drug Abuse.\nSet a quit date and develop a treatment plan with a study therapist.\nTake Chantix (varenicline) every day for a period of 12 weeks.\nMeet for weekly and biweekly counseling sessions with a therapist.\nAnswer questionnaires about how you think and feel.\n\nPhase 3\n\nThis study will involve three visits to the National Institute on Drug Abuse.\nComplete an MRI scanning session that will last about 20min each visit\nMeet with a study staff member on each visit who will ask you questions about your smoking behavior and how you think and feel.", "DetailedDescription":"Objective\n\nThe primary objective of the current protocol is to gain a greater understanding of the neurobiological mechanisms underlying acute nicotine withdrawal and contributing to the maintenance of, or return to smoking behavior among nicotine-dependent individuals, in the service of developing future smoking cessation treatments. The Nicotine Withdrawal Syndrome is a major cause of failed quit attempts in smokers, and targeting this time period for intervention may help improve smoking cessation outcomes.\n\nStudy Population\n\nWe will recruit treatment seeking and non-treatment seeking smokers, as well as matched non-smoker control participants.\n\nDesign\n\nThere are 3 arms included in this protocol, each of which aims to understand the neurobiology of the Nicotine Withdrawal Syndrome during the initial quit period, with the broader goal of increasing quit success rate in the future.\n\nMain Study: To understand (1) the acute neurobiological effects of nicotine withdrawal on treatment-seeking and non-treatment seeking smokers, (2) the long term neurobiological outcomes of varenicline treatment and smoking cessation counseling at 1, 6, and 12 months. We will recruit 85 treatment seeking and 35 non-treatment seeking smokers for a within (nicotine deprivation), between (treatment-seeking status) subjects randomized, double blind, placebo controlled study.\n\nMotivational Interviewing Arm: (1) To increase motivation and preparation for smoking cessation treatment among individuals who express an interest in quitting smoking but are not currently ready to enter treatment, in the service of increasing quit success rate and (2) to understand the neurobiological basis of motivation to quit smoking, and the interaction between motivation to quit and mechanisms that underlie acute nicotine withdrawal. We will recruit 300 current smokers interested in quitting smoking, but not yet ready to set a quit date.\n\nTranscranial Direct Current Stimulation (tDCS) Arm: To understand the acute effect of tDCS on 3 large-scale brain networks dysregulated in nicotine addiction and withdrawal, the Default Mode Network, the Executive Control Network, and the Salience Network. We will enroll 60 non-treatment seeking smokers, with the expectation of 35 completers; and enroll 55 non-smoking controls, with the expectation of 45 completers, for a double blind, sham controlled, randomized crossover study. Smokers will be studied in nicotine abstinence and nicotine sated conditions, as in the Main Study design.\n\nOutcome measures\n\nPrimary outcome measures:\n\nChange in BOLD signal and FC related to task parameters, between drug (or tDCS) condition.\nBehavioral performance on each of the tasks assessing inhibitory control processes, reward responsiveness, amygdala, striatal, BNST reactivity, impulsive decision making, cue reactivity and working memory (e.g., reaction time, error rate, hit rate, reward bias).\nSelf-reported craving, withdrawal symptoms and mood/affect\nSmoking abstinence as determined by self-reported tobacco use, urine cotinine, and breath CO.\n\nSecondary outcome measures:\n\nMRS for glutamate concentration.\nPlasma ACTH and cortisol.\nResting state CBF from ASL.\nERP and EEG measures.\nRatings and scores on self-report characterization measures.\nStructural MRI and DTI data.\nResting state FC at 1, 6 and 12 months post-treatment." }, "ConditionsModule":{ "ConditionList":{ "Condition":[ "Nicotine Dependence" ] }, "KeywordList":{ "Keyword":[ "fMRI", "tDCS" ] } }, "DesignModule":{ "StudyType":"Interventional", "PhaseList":{ "Phase":[ "Not Applicable" ] }, "DesignInfo":{ "DesignAllocation":"Randomized", "DesignInterventionModel":"Crossover Assignment", "DesignPrimaryPurpose":"Basic Science", "DesignMaskingInfo":{ "DesignMasking":"Triple", "DesignWhoMaskedList":{ "DesignWhoMasked":[ "Participant", "Investigator", "Outcomes Assessor" ] } } }, "EnrollmentInfo":{ "EnrollmentCount":"577", "EnrollmentType":"Anticipated" } }, "ArmsInterventionsModule":{ "ArmGroupList":{ "ArmGroup":[ { "ArmGroupLabel":"active tDCS", "ArmGroupType":"Active Comparator", "ArmGroupDescription":"(1) anodal left-dlPFC + cathodal rightvmPFC stimulation, with anode over the left dlPFC and cathode over the right-vmPFC; (2) cathodal left-dlPFC + anodal right-vmPFC stimulation, in which polarity is reversed between the two electrodes", "ArmGroupInterventionList":{ "ArmGroupInterventionName":[ "Device: Transcranial Direct Current Stimulation" ] } },{ "ArmGroupLabel":"sham tDCS", "ArmGroupType":"Sham Comparator", "ArmGroupDescription":"To simulate the experience of tDCS stimulation, current is ramped on and turned off at the beginning and end of the tDCS session. An additional sham option is to have the current ramp up and down only at the beginning of the sham session, and not at the end. This second sham is supported in the literature as an effective blinding technique, which subjects cannot distinguish from active stimulation. One of these sham options will be used for data that will be analyzed together, to be determined based on equipment capabilities and preliminary analysis of blinding efficacy in our cross over design. We will assess the efficacy of sham condition by providing participants and the investigator with a questionnaire on the MRI/tDCS session, wherein they will report whether they thought the tDCS session was active or sham. The MRIoperator (or other non protocol personnel) will control active/sham conditions.", "ArmGroupInterventionList":{ "ArmGroupInterventionName":[ "Device: Sham" ] } } ] }, "InterventionList":{ "Intervention":[ { "InterventionType":"Device", "InterventionName":"Transcranial Direct Current Stimulation", "InterventionDescription":"Transcranial Direct Current Stimulation (tDCS), a type of Non-invasive Brain Stimulation (NIBS), has the potential to modify neuronal circuits by application of a subthreshold conductive current through the scalp. Two potential targets for tDCS as a smoking cessation aid are the dorsolateral prefrontal cortex (dlPFC), a node of the ECN, and the ventromedial prefrontal cortex (vmPFC), a node of the DMN. tDCS can potentially strengthen the control of the ECN through excitatory stimulation of the dlPFC, and weaken the influence of the DMN by inhibitory stimulation of the vmPFC. The tDCS model we will use is the neuroConn DCStimulator MR (neuroCare Group GmbH, Munchen, Germany).", "InterventionArmGroupLabelList":{ "InterventionArmGroupLabel":[ "active tDCS" ] } },{ "InterventionType":"Device", "InterventionName":"Sham", "InterventionDescription":"Sham Comparator", "InterventionArmGroupLabelList":{ "InterventionArmGroupLabel":[ "sham tDCS" ] } } ] } }, "OutcomesModule":{ "PrimaryOutcomeList":{ "PrimaryOutcome":[ { "PrimaryOutcomeMeasure":"MRI BOLD signal and FC", "PrimaryOutcomeDescription":"Change in BOLD signal and Functional Connectivity related to task parameters, between tDCS conditions.", "PrimaryOutcomeTimeFrame":"each scan visit ( 2 days)" },{ "PrimaryOutcomeMeasure":"Behavioral tasks", "PrimaryOutcomeDescription":"Behavioral performance on each of the tasks assessing inhibitory control processes, reward responsiveness, amygdala, striatal, BNST reactivity, impulsive decision making, cue reactivity and working memory (e.g., reaction time, error rate, hit rate, reward bias).", "PrimaryOutcomeTimeFrame":"each scan visit (2 days)" } ] } }, "EligibilityModule":{ "EligibilityCriteria":"INCLUSION CRITERIA:\n\nAll Subjects must:\n\nBe between the ages of 18-65.\nBe right-handed. Assessment tool(s): Edinburgh Handedness Inventory.\nBe in good health. Justification: Many illnesses may alter fMRI signals as well as cognitive processes and neural functioning. Assessment tool(s): Participants will provide a brief health history during phone screening, and undergo a medical history and physical examination with a qualified IRP clinician.\nBe free of current moderate to severe DSM-V Substance Use Disorder on any drug, except nicotine in smokers. Those with past moderate to severe use disorder on substances may be included, provided they are in sustained remission (and not on maintenance therapy for opioid use disorder) and are not intoxicated on the day of the imaging session. Justification: Moderate to severe use disorder on other substances may result in unique CNS deficits that could confound results and introduce excessive variance, while mild substance use disorder and substance use disorder in remission are common in community samples of smokers. Assessment tool(s): Computerized SCID or comparable assessment and DSM-5 substance use disorder assessment.\nBe able to abstain from alcohol and other recreational drugs for 24 hours before each imaging session, and able to moderate caffeine intake 12 hours before each imaging session. Justification: Recent substance use, including alcohol, and caffeine modulate neural functioning in a way that would complicate data interpretation. Assessment tool(s): Self-report, breathalyzer, and urine toxicology screen with follow up neuromotor assessment to ensure absence of acute impairment with positive urine test.\n\nSmokers must meet the additional criteria:\n\nHave a urine cotinine (NicAlert) level of 4 or higher and have been smoking for at least 1 year. Justification: The present protocol is interested in neurobiological mechanisms that underlie nicotine withdrawal, and is thus contingent on the presence of nicotine dependence. Assessment tool(s): Selfreport, NicAlert of 4 or higher\nBe able to abstain from smoking for 12 hours prior to MRI-tDCS study sessions. Justification: The present protocol will investigate the effect of acute nicotine withdrawal on cognitive processes and response to tDCS. Assessment: Self-report and expired CO levels\n\nIn addition, non-smokers must meet:\n\nNot have a history of daily cigarette smoking or have used any nicotine products continuously lasting more than a month, and no smoking or continuous use of any nicotine products within the past year. Assessment Tools: Self-report, NicAlert, and expired CO levels.\n\nEXCLUSION CRITERIA:\n\nAll participants will be excluded if they:\n\nAre not suitable to undergo an fMRI experiment due to certain implanted devices (cardiac pacemaker or neurostimulator, some artificial joints, metal pins, surgical clips or other implanted metal parts), body morphology, or claustrophobia. Justification: MR scanning is one of the primary measurement tools used in the protocol. Assessment tool(s): Prospective participants will fill out an MRI screening questionnaire and undergo an interview with an MR technologist. Questions concerning suitability for scanning will be referred to the MR Medical Safety Officer. Prospective participants will be questioned about symptoms of claustrophobia and placed in the mock scanner during their first visit to assess for possible difficulty tolerating the confinement of the scanner and for ability to fit into the scanner.\nHave musculoskeletal abnormalities restricting an individual s ability to lie flat for extended periods of time. Justification: MR scanning sessions require participants to lie flat on their backs and remain perfectly still for approximately one hour. Therefore, conditions that would make that difficult (e.g. chronic back pain, significant scoliosis) will be exclusionary. Assessment tool(s): History and physical examination by a qualified IRP clinician, supplemented with a trial of lying in the mock scanner to assess comfort issues.\nHave HIV or Syphilis. Justification: HIV and Syphilis both can have central nervous system (CNS) sequelae, thus introducing unnecessary variability into the data. Assessment tool(s): Oral HIV followed by blood test if oral test is + and STS+ without adequate prior treatment\nRegularly or intermittently use any prescription (e.g., benzodiazepines, barbiturates), over-the-counter (e.g., cold medicine) medications that are likely to alter BOLD signal (neuronal-vascular coupling). Justification: The use of these substances may alter the fMRI signal and/or neural functions of interest in the current study. Assessment tool(s): History and comprehensive urine drug screening to detect benzodiazepines, antipsychotics, anticonvulsants, and barbiturates. Note: If a participant is intermittently taking a medication likely to affect BOLD signal, the participant may be excluded or if scanned, will be scanned in the same medication state for data continuity purposes (i.e. either all scan days are scheduled after 5 half-lives since last medication use; or all scan days are scheduled on medication).\nHave any current neurological illnesses including, but not limited to, seizure disorders, frequent migraines or on prophylaxis, multiple sclerosis, cerebrovascular accident, movement disorders (except essential tremor, so long as it would not interfere with study tasks such as button pressing), history of significant head trauma, or CNS tumor. Justification: Neurological diseases alter CNS function and, possibly, the neuronal-vascular coupling that forms the basis of the fMRI signal. Assessment tool(s): History and physical examination by a qualified IRP clinician, urine drug screening for anticonvulsants not disclosed by history. History of head trauma with loss of consciousness of more than 30 minutes or with post-concussive sequelae lasting more than two days, regardless of loss of consciousness, will be exclusionary. The MAI who will also retain discretion to exclude based on a history of neurological illness that may compromise data integrity.\nHave current major psychotic disorders, mania, substance-induced psychiatric disorders, or any current suicidal ideations or history of suicide attempts. Moderate to severe current symptoms of mood or anxiety disorders will be exclusionary as well. However, mild mood or anxiety disorder symptoms will not be exclusionary, whether medicated or unmedicated. The MAI will reserve the right to exclude on the basis of psychiatric history not explicitly described in this criterion. Justification: Psychiatric disorders involve the central neural system (CNS) and, therefore, can be expected to alter the fMRI measures being used in this study, however, some degree of mood and anxiety symptoms are common in community samples of smokers. Assessment tool(s): Computerized SCID or comparable assessment, and clinical interview confirmation by clinician.\nAre cognitively impaired or learning disabled. Justification: Cognitive impairment and learning disabilities may be associated with altered brain functioning in regions recruited during laboratory task performance. Cognitive impairment may affect one s ability to give informed consent. Assessment tool(s): History of placement in special-education classes as a consequence of serious learning problems and not solely as a consequence of behavioral problems, assessed during the History and Physical screening assessment.\nHave significant cardiovascular conditions that would make use of nicotine patch unsafe. Justification: Nicotine patch may cause significant arrhythmias in susceptible individuals. Assessment tool(s): History and physical exam, including 12-lead EKG.\n\nHave any other major medical condition, such as diabetes mellitus, that in the view of the investigators would compromise the safety of an individual during participation, or the quality of data obtainable. Justification: Many illnesses not explicitly covered here may increase risk or alter important outcome measures. Assessment tool(s): History and physical examination by a qualified IRP clinician and CBC, urinalysis, NIDA chemistry panel (liver function tests, electrolytes, kidney function). The following lab values will result in exclusion from the study:\n\ni. Hemoglobin < 10 g/dl\n\nii. White Blood Cell Count < 2400/microl\n\niii. Liver Function Tests > 3X upper limit of normal\n\niv. Serum glucose > 200 mg/dl\n\nv. Urine protein > 2+\n\nvi. Serum creatinine > 2 mg/dl\n\nThe MAI will retain discretion to exclude based on less extreme lab results. After the screening process has been completed, the MAI will take into account all data collected in order to decide if there is an existing medical illness that would compromise participation in this research.\n\nPregnant, planning to become pregnant, or breastfeeding. Females are instructed in the consent to use effective forms of birth control during the study period. Justification: study procedures and drugs used in the current protocol may complicate pregnancy or be transferred to nursing children. Assessment tool(s): Urine and/or serum pregnancy tests, and clinical interview. Urine pregnancy tests will be conducted at the beginning of each imaging visit.\n\nThe following exclusion criteria are new for the tDCS study:\n\nParticipated in any brain stimulation session less than two weeks ago, or underwent brain stimulation exposure for treatment purposes in the last 6 months, including tDCS or transcranial magnetic stimulation (TMS). Justification: Prior exposure to brain stimulation may result in carry-over effects that could confound the results of this study. Participants may enroll in the study once the listed time periods have passed. Assessment tool(s): Participant medical history and physical (H&P).", "HealthyVolunteers":"Accepts Healthy Volunteers", "Gender":"All", "MinimumAge":"18 Years", "MaximumAge":"55 Years", "StdAgeList":{ "StdAge":[ "Adult" ] } }, "ContactsLocationsModule":{ "CentralContactList":{ "CentralContact":[ { "CentralContactName":"Elliot Stein, Ph.D.", "CentralContactRole":"Contact", "CentralContactPhone":"(443) 740-2650", "CentralContactEMail":"estein@mail.nih.gov" } ] }, "OverallOfficialList":{ "OverallOfficial":[ { "OverallOfficialName":"Elliot Stein, Ph.D.", "OverallOfficialAffiliation":"National Institute on Drug Abuse (NIDA)", "OverallOfficialRole":"Principal Investigator" } ] }, "LocationList":{ "Location":[ { "LocationFacility":"National Institute on Drug Abuse", "LocationStatus":"Recruiting", "LocationCity":"Baltimore", "LocationState":"Maryland", "LocationZip":"21224", "LocationCountry":"United States", "LocationContactList":{ "LocationContact":[ { "LocationContactName":"For more information contact Mathew's Media Group Recruiting", "LocationContactRole":"Contact", "LocationContactPhone":"800-535-8254", "LocationContactEMail":"researchstudies@mail.nih.gov" } ] } } ] } } }, "DerivedSection":{ "MiscInfoModule":{ "VersionHolder":"April 22, 2020" }, "ConditionBrowseModule":{ "ConditionMeshList":{ "ConditionMesh":[ { "ConditionMeshId":"D000014029", "ConditionMeshTerm":"Tobacco Use Disorder" } ] }, "ConditionAncestorList":{ "ConditionAncestor":[ { "ConditionAncestorId":"D000019966", "ConditionAncestorTerm":"Substance-Related Disorders" },{ "ConditionAncestorId":"D000064419", "ConditionAncestorTerm":"Chemically-Induced Disorders" },{ "ConditionAncestorId":"D000001523", "ConditionAncestorTerm":"Mental Disorders" } ] }, "ConditionBrowseLeafList":{ "ConditionBrowseLeaf":[ { "ConditionBrowseLeafId":"M15368", "ConditionBrowseLeafName":"Tobacco Use Disorder", "ConditionBrowseLeafAsFound":"Nicotine Dependence", "ConditionBrowseLeafRelevance":"high" },{ "ConditionBrowseLeafId":"M20421", "ConditionBrowseLeafName":"Substance-Related Disorders", "ConditionBrowseLeafRelevance":"low" },{ "ConditionBrowseLeafId":"M28889", "ConditionBrowseLeafName":"Chemically-Induced Disorders", "ConditionBrowseLeafRelevance":"low" },{ "ConditionBrowseLeafId":"M3396", "ConditionBrowseLeafName":"Mental Disorders", "ConditionBrowseLeafRelevance":"low" },{ "ConditionBrowseLeafId":"M13056", "ConditionBrowseLeafName":"Psychotic Disorders", "ConditionBrowseLeafRelevance":"low" } ] }, "ConditionBrowseBranchList":{ "ConditionBrowseBranch":[ { "ConditionBrowseBranchAbbrev":"BC25", "ConditionBrowseBranchName":"Substance Related Disorders" },{ "ConditionBrowseBranchAbbrev":"BXM", "ConditionBrowseBranchName":"Behaviors and Mental Disorders" },{ "ConditionBrowseBranchAbbrev":"All", "ConditionBrowseBranchName":"All Conditions" } ] } } } } } }