[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT05866471":3,"trial-entities:NCT05866471":134,"trial-summary:NCT05866471":137},{"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":22,"study_type":26,"primary_purpose":27,"phases":28,"enrollment_info":30,"interventions":33,"primary_outcomes":59,"secondary_outcomes":75,"sex":76,"minimum_age":77,"maximum_age":78,"healthy_volunteers":79,"eligibility_criteria":80,"std_ages":101,"locations":104,"central_contacts":122,"overall_officials":125,"references":129,"see_also_links":130},"NCT05866471","2024-0463","The ENHANCE Study: taVNS and Psilocybin","Activating Neuroplasticity to ENHANCE the Perception Box Expanding Effects of Psilocybin","RECRUITING","2028-01","2026-07","2026-07-29","2025-01-27","University of Wisconsin, Madison","OTHER",null,"This study will examine whether combining a single dose of psilocybin with non-invasive transcutaneous auricular vagus nerve stimulation (taVNS), a potential inducer of neuroplasticity and enhanced memory formation, will enhance the long-term beneficial behavioral effects of psilocybin when compared to sham taVNS or no VNS by allowing memory for insights gained during the psychedelic experience to remain vivid after they will have faded in subjects who receive psilocybin followed by sham taVNS or no VNS.","One hundred and eight medically healthy adult volunteers with a modest decrement in wellbeing will receive a single open-label 25 mg dose of psilocybin administered within a \"set and setting\" (SaS) framework of psychological support provided by trained facilitators, such as has been successfully employed in prior psychedelic studies at UW-Madison. The SaS protocol will include 2-4 hours of preparation, a 6- to 8-hour psilocybin dosing session and an hour-long integration session 1 day and 9 days post dosing. All subjects will receive various combinations of active taVNS or sham taVNS prior to, or following, psilocybin dosing.\n\nActive and sham taVNS sessions will last 20 minutes and will occur twice daily (morning and afternoon\u002Fevening) for 7 consecutive days, using an \"at home\" protocol that has been used safely and effectively by study collaborators. taVNS is a non-invasive low-risk procedure.\n\nSubjects will be randomized with equal allocation to one of four conditions: 1) seven days of sham taVNS prior to psilocybin dosing and 7 days of active taVNS post- psilocybin dosing (Group 1: n=27); 2) seven days of sham taVNS prior to psilocybin dosing and 7 days of sham taVNS post- psilocybin dosing (Group 2: n=27); 3) seven days of sham taVNS prior to psilocybin dosing and psilocybin with psychosocial support post-dosing (Group 3: n=27); and 4) seven days of active taVNS prior to psilocybin dosing and 7 days of sham taVNS post- psilocybin dosing (Group 4: n=27). Importantly, participants in all groups will receive psychosocial support in addition to their randomization status (i.e., taVNS or sham taVNS prior to, or following psilocybin, or psychosocial support alone), as the provision of psychosocial support is the current standard of care for the use of psychedelics in FDA-regulated clinical trials (FDA 2023). It is anticipated that a total sample of 108 subjects will be enrolled to provide 100 subjects who complete study activities\u002Fassessments sufficient to provide evaluable data for testing study primary and exploratory outcomes.",[19,20,21],"Healthy","Psychedelic Experiences","Vagus Nerve Stimulation",[23,24,21,25],"Psilocybin","Psychedelics","Healthy Volunteer","INTERVENTIONAL","BASIC_SCIENCE",[29],"PHASE1",{"count":31,"type":32},108,"ESTIMATED",[34,46,51,56],{"type":35,"name":23,"description":36,"armGroupLabels":37,"otherNames":42},"DRUG","The psilocybin is produced under Good Manufacturing Practice and is in a capsule that contains 25 mg of botanically-derived psilocybin.",[38,39,40,41],"Group 1: Sham taVNS + Psilocybin + taVNS","Group 2: Sham taVNS + Psilocybin + Sham taVNS","Group 3: Sham taVNS + Psilocybin + Psychosocial Support Alone","Group 4: taVNS + Psilocybin + Sham taVNS",[43,44,45],"Psilocybine, Psilocibin","Filament Health Psilocybin","PEX010",{"type":47,"name":48,"description":49,"armGroupLabels":50},"DEVICE","Transcutaneous auricular Vagus Nerve Stimulation (taVNS)","For both the active and sham taVNS procedure, participants will be provided with, and trained on, taVNS devices that apply gentle stimulation to the left ear via either electrodes or an earpiece that fits over the left ear.",[38,41],{"type":52,"name":53,"description":54,"armGroupLabels":55},"BEHAVIORAL","Psychosocial Support Alone","Participants assigned to Psychosocial Support Alone will not receive taVNS following psilocybin dosing.",[40],{"type":14,"name":57,"description":49,"armGroupLabels":58},"Sham taVNS",[38,39,40,41],[60,64,68,71],{"measure":61,"description":62,"timeFrame":63},"Memory Experiences Questionnaire (MEM-Q-PSIL): Comparison of taVNS Administration vs. Treatment as Usual","The MEM-Q is 31-item self-report scales designed to measure 10 phenomenological qualities of autobiographical memories: Vividness, Coherence, Accessibility, Time Perspective, Sensory Details, Visual Perspective, Emotional Intensity, Sharing, Distancing and Valence. Ratings are made on a 5-point Likert scale, ranging from 1 (strongly disagree) to 5 (strongly agree).","8 weeks",{"measure":65,"description":66,"timeFrame":67},"Functional Magnetic Resonance Imaging (fMRI): Comparison of taVNS Administration vs. Treatment as Usual","Activation in brain regions associated with cued autobiographical memory retrieval will be assessed with fMRI. Group comparisons will examine differences in whole brain blood oxygenated level dependent (BOLD) signal and connectivity based on previously established seed-based methods using a priori brain regions implicated in autobiographical memory retrieval corresponding dosing session stimuli. The study team will update with more specific information when the details are confirmed.","Day 1 and Day 56 Post- Psilocybin Dose",{"measure":69,"description":70,"timeFrame":63},"Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS): Comparison of taVNS Administration vs. Treatment as Usual","The WEMWBS is a 14-item self-report scale that was designed to measure the psychological well-being of a population. The questions use a five-point Likert scale. The items are all worded positively and cover both feeling and functioning aspects of mental wellbeing. Items on the questionnaire are rated on a 5-point scale, where 1= \"None of the time\", 2= \"rarely\", 3= \"some of the time\", 4= \"often\", 5= \"all the time\". A total scale score is calculated by summing the 14 individual item scores. The total possible range of scores for the WEMWBS is 14-70 with higher scores indicating a greater well-being.",{"measure":72,"description":73,"timeFrame":74},"Summary of Adverse Events","Adverse events (AEs) categorized by CTCAE v5.0 criteria at all assessments (6 study visits).","up to 8 weeks",[],"ALL","18 Years","70 Years",true,{"inclusion":81,"exclusion":85,"raw_text":100},[82,83,84],"English speaking","Ability\u002Fwillingness to complete all study activities","Modest reduction in emotional well-being",[86,87,88,89,90,91,92,93,94,95,96,97,98,99],"Blood pressure and heart rate within established ranges at screening","Use of acceptable contraceptive methods (sexually active males and women of childbearing potential)","Clinically significant safety lab abnormalities (i.e., Complete Blood Count with Differential, Comprehensive Metabolic Panel, and urinalysis)","Current or clinically significant psychiatric disorder that, in the investigator's judgment, would interfere with participation or increase risk","Current use of drugs or medications, prescribed or otherwise, that may interact with psilocybin","Use of investigational drugs, biologics, or devices within 30 days of enrollment","Use of psychedelic or related agents within three months of Dosing Day","Clinically significant electrocardiogram (ECG)","Vitals outside acceptable range","Pregnancy and currently breastfeeding","Unwillingness to go without tobacco products for 12 hours or more","Inability to undergo fMRI scanning","Recent ear trauma, hearing loss (if clinically significant), or deafness","Family history of a psychotic disorder in a first degree relative","Inclusion Criteria:\n\n* English speaking\n* Ability\u002Fwillingness to complete all study activities\n* Modest reduction in emotional well-being\n* Medically healthy (does not meet criteria for an exclusionary medical condition)\n* Blood pressure and heart rate within established ranges at screening\n* Use of acceptable contraceptive methods (sexually active males and women of childbearing potential)\n\nExclusion Criteria:\n\n* Clinically significant safety lab abnormalities (i.e., Complete Blood Count with Differential, Comprehensive Metabolic Panel, and urinalysis)\n* Current or clinically significant psychiatric disorder that, in the investigator's judgment, would interfere with participation or increase risk\n* Current use of drugs or medications, prescribed or otherwise, that may interact with psilocybin\n* Use of investigational drugs, biologics, or devices within 30 days of enrollment\n* Use of psychedelic or related agents within three months of Dosing Day\n* Clinically significant electrocardiogram (ECG)\n* Vitals outside acceptable range\n* Pregnancy and currently breastfeeding\n* Unwillingness to go without tobacco products for 12 hours or more\n* Inability to undergo fMRI scanning\n* Recent ear trauma, hearing loss (if clinically significant), or deafness\n* Family history of a psychotic disorder in a first degree relative",[102,103],"ADULT","OLDER_ADULT",[105],{"facility":106,"status":8,"city":107,"state":108,"zip":109,"country":110,"contacts":111,"geoPoint":119},"University of Wisconsin - Madison","Madison","Wisconsin","53715","United States",[112,116],{"name":113,"role":114,"email":115},"Program Manager","CONTACT","enhance@psychiatry.wisc.edu",{"name":117,"role":118},"Christopher Nicholas, PhD","SUB_INVESTIGATOR",{"lat":120,"lon":121},43.07305,-89.40123,[123],{"name":113,"role":114,"phone":124,"email":115},"608-265-4987",[126],{"name":127,"affiliation":13,"role":128},"Charles Raison, MD","PRINCIPAL_INVESTIGATOR",[],[131],{"label":132,"url":133},"Take the pre-screening survey","https:\u002F\u002Fredcap.wisc.edu\u002Fsurveys\u002F?s=RTTDHYJJ7TKKN9C8",{"nct_id":4,"conditions":135,"biomarkers":136},[25],[],{"nct_id":4,"found":79,"summary":138,"prompt_version":148},{"design":139,"status":140,"heading":141,"summary":142,"follow_up":143,"word_count":144,"commitments":145,"compensation":146,"drugs_mentioned":147},"This interventional study plans to enroll 108 healthy adult volunteers. Participants will be randomized into one of four groups, receiving different combinations of active or sham taVNS before and after a single open-label 25 mg dose of psilocybin.","completed","The ENHANCE Study: Psilocybin and Vagus Nerve Stimulation","This study, called the ENHANCE Study, is looking at whether combining a single dose of psilocybin (a psychedelic compound) with transcutaneous auricular Vagus Nerve Stimulation (taVNS), a gentle electrical stimulation applied to the ear, can improve well-being. Researchers want to see if this combination helps people remember positive insights from their psychedelic experience for longer. You might be eligible if you are a healthy adult between 18 and 70 years old, speak English, and have a modest reduction in your emotional well-being. The study will measure success by looking at your memory of the experience, brain activity using fMRI (functional Magnetic Resonance Imaging), and overall mental well-being after 8 weeks. The current status of this study is unclear.","Your memory experiences and mental well-being will be assessed at 8 weeks. Functional MRI will be conducted at Day 1 and Day 56 after the psilocybin dose.",118,"You would receive a single 25 mg dose of psilocybin with psychological support. You would also use a taVNS device at home twice daily for 20 minutes for 7 consecutive days, either before or after psilocybin dosing. There will be preparation and integration sessions, and assessments at Day 1, Day 56, and 8 weeks post-psilocybin dose.","Not stated in the trial record.",[23,48],"v2"]