[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100475940":3},{"organization":4,"outcomesModule":7,"designInfo":89,"detailedDescription":102,"studyPopulation":16,"armGroups":103,"interventions":116,"overallOfficials":127,"centralContacts":131,"locations":137,"responsibleParty":176,"collaborators":178,"id":185,"slug":16,"hasResults":186,"nctId":187,"briefTitle":188,"officialTitle":189,"acronym":190,"eligibilityCriteria":191,"healthyVolunteers":186,"sex":192,"minAge":193,"maxAge":194,"enrollmentInfo":195,"targetDuration":16,"studyType":198,"phases":199,"briefSummary":201,"conditions":202,"keywords":204,"overallStatus":140,"whyStopped":16,"lastUpdateSubmitDate":206,"lastUpdatePostDateStruct":207,"startDateStruct":210,"completionDateStruct":212,"leadSponsor":214,"locationsCount":215},{"fullName":5,"class":6},"Radboud University Medical Center","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":13,"otherOutcomes":80},[9],{"measure":10,"description":11,"timeFrame":12},"Mean change in weekly attack frequency, across treatments groups.","In week 3 post-randomization, compared to the 4-week baseline average per week","week 3 of treatment",[14,18,22,25,28,30,33,36,38,41,43,45,46,48,50,54,58,61,64,68,72,76],{"measure":15,"description":16,"timeFrame":17},"Mean change in weekly attack frequency across weeks 4-8 compared to the 4-week baseline and for each week separately.",null,"week 8 post-randomization",{"measure":19,"description":20,"timeFrame":21},"100% reduction (remission rate) in number of weekly attacks in the third treatment week, compared to the 4-week baseline, across treatment groups.","Rate of subjects with 100% reduction in weekly attack frequency compared to baseline","week 3 post-randomization",{"measure":23,"description":24,"timeFrame":21},"≥50% reduction (50% responder rate) in number of weekly attacks in the third treatment week, compared to the 4-week baseline, across treatment groups.","Rate of subjects with more than 50% reduction in weekly attack frequency compared to baseline",{"measure":26,"description":27,"timeFrame":21},"≥30% reduction (30% responder rate) in number of weekly attacks in the third treatment week, compared to the 4-week baseline, across treatment groups.","Rate of subjects with more than 30% reduction in weekly attack frequency compared to baseline",{"measure":29,"description":20,"timeFrame":17},"100% reduction (remission rate) in number of weekly attacks across weeks 4-8 compared to the 4-week baseline and for each week separately.",{"measure":31,"description":32,"timeFrame":17},"≥50% reduction (50% responder rate) in number of weekly attacks across weeks 4-8 compared to the 4-week baseline and for each week separately.","Rate of subjects with 50% reduction in weekly attack frequency compared to baseline",{"measure":34,"description":35,"timeFrame":17},"≥30% reduction (30% responder rate) in number of weekly attacks across weeks 4-8 compared to the 4-week baseline and for each week separately.","Rate of subjects with 30% reduction in weekly attack frequency compared to baseline",{"measure":37,"description":16,"timeFrame":21},"Mean change in weekly attack frequency in the entire 3 week treatment period compared to the 4-week baseline.",{"measure":39,"description":40,"timeFrame":21},"Mean change in mean headache attack duration (minutes) per week, across treatment groups","In week 3 compared to the weekly average during 4-week baseline",{"measure":39,"description":42,"timeFrame":17},"Across weeks 4-8 compared to the 4-week baseline and for each week separately.",{"measure":44,"description":40,"timeFrame":21},"Mean change in mean headache attack severity (VAS 1-10), across treatment groups",{"measure":44,"description":42,"timeFrame":17},{"measure":47,"description":40,"timeFrame":21},"Mean change in number of abortive medication use, across treatment groups",{"measure":47,"description":49,"timeFrame":17},"Across weeks 4-8 compared to the 4-week baseline",{"measure":51,"description":52,"timeFrame":53},"Failure of sustained response'","Time to initiation of additional prophylactic treatment and\u002For GON-block during weeks 4-8, across treatment groups","Weeks 4-8 post-randomization",{"measure":55,"description":56,"timeFrame":57},"Patient Global Impression of Change (PGIC)","Patient Global Impression of Change at week 3 post-randomization; scale 0-7, higher scores representing better improvement","Day 21 post-randomization",{"measure":55,"description":59,"timeFrame":60},"Patient Global Impression of Change at week 8 post-randomization; scale 0-7, higher scores representing better improvement","weeks 3 and 8",{"measure":62,"description":63,"timeFrame":60},"Health-related quality of life","Change from baseline in EQ-5D-5L Visual Analogue Scale (VAS) at weeks 3 and 8.",{"measure":65,"description":66,"timeFrame":67},"Hospital Anxiety and Depression Score (HADS)","Change from baseline in Hospital Anxiety and Depression Scale (HADS) at weeks 3 and 8.","weeks 3 and 8.",{"measure":69,"description":70,"timeFrame":71},"Pharmacokinetic (PK)-pharmacodynamic (PD) modelling","Plasma LSD concentrations on day 18 post-randomization frequency","Day 18 post-randomization",{"measure":73,"description":74,"timeFrame":75},"Cost-effectiveness analysis (CEA) from a societal perspective comparing the LSD intervention with usual care.","Healthcare use and productivity losses will be measured by patient questionnaires (iMCQ, and iPCQ)","Week 1, 3 and 8",{"measure":77,"description":78,"timeFrame":79},"Efficacy of treatment masking","measured as perceived treatment assignment on a 5-point scale (likely verum\u002Fpossibly verum\u002Fdon't know\u002Fpossibly placebo\u002Flikely placebo).","Week 1 and 3 post-randomization",[81,85],{"measure":82,"description":83,"timeFrame":84},"Alcohol consumption","Units of alcohol consumed during baseline, treatment and follow-up","during the entire 12-week duration of the study",{"measure":86,"description":87,"timeFrame":88},"PK-PD modelling","Correlation between individual pharmacokinetics of LSD and relative change of weekly attack frequency","Week 1 and 3",{"allocation":90,"interventionModel":91,"interventionModelDescription":92,"primaryPurpose":93,"observationalModel":16,"timePerspective":16,"maskingInfo":94},"RANDOMIZED","PARALLEL","3-week double-blind placebo-controlled intervention study, preceded by a 4-week baseline observation period and followed by 5 weeks post-treatment observation period.","TREATMENT",{"masking":95,"maskingDescription":96,"whoMasked":97},"QUADRUPLE","Study drug or placebo are similar in appearance, taste and smell",[98,99,100,101],"PARTICIPANT","CARE_PROVIDER","INVESTIGATOR","OUTCOMES_ASSESSOR","Treatment of cluster headache consists of acute remedies for attacks (mainly 100% O2, sumatriptan), transitional treatment for temporary frequency reduction (subcutaneous steroid injection at the greater occipital nerve (GON block), oral steroids or frovatriptan) and prolonged prophylaxis (e.g. verapamil, lithium, topiramate). Although the latter compounds have shown some efficacy in reducing the attack frequency, the evidence for their effect is weak. All current prophylactics are prescribed off-label and are limited in their utility due to associated side effects. Despite treatment, many (notably chronic) cluster headache patients continue suffering headache attacks.\n\nInvasive, expensive treatments like hypothalamic deep brain stimulation, occipital nerve stimulation and sphenopalatine ganglion stimulation are last resort options. Recently, a monoclonal antibody targeting calcitonin gene related peptide (CGRP) received FDA approval for episodic cluster headache, but was shown to be ineffective in cCH. Thus, there is a considerable unmet need for effective treatments that are better tolerated, safe and affordable.\n\nIn this study, the investigators will assess the efficacy of prophylactic treatment with LSD in cCH. The evidence for the efficacy of LSD is limited, with the majority of data originating from case reports or uncontrolled and retrospective (internet) surveys. Nevertheless, these studies do provide indications that LSD may hold potential as a cluster headache prophylaxis.\n\nThe primary objective of this randomized double-blind placebo-controlled trial is to compare the efficacy of LSD 25μg every 3 days for 3 weeks versus placebo in cCH. The investigators aim to show that, at the end of treatment, verum is more efficacious than placebo with comparable tolerability in an ambulatory setting. To explore the sustainability of benefit the investigators will also assess the (sustained) response at 5 weeks post-treatment (8 weeks postrandomization).\n\nIf the study findings are positive, LSD should be further studied before use in routine clinical practice. Non-hallucinogenic low-dosed LSD may provide an alternative or adjunctive option for patients who do not respond to or cannot tolerate currently available treatments.",[104,110],{"label":105,"type":106,"description":107,"interventionNames":108},"Verum","EXPERIMENTAL","Lysergic diethylamide tartrate (equivalent to 25 microgram LSD base), one dose every 3 days for 3 weeks (totalling 7 vials)",[109],"Drug: LSD tartrate",{"label":111,"type":112,"description":113,"interventionNames":114},"Placebo","PLACEBO_COMPARATOR","Placebo vial looking like verum vial, one vial every 3 days for 3 weeks (totalling 7 vials)",[115],"Drug: Placebo",[117,124],{"type":118,"name":119,"description":120,"armGroupLabels":121,"otherNames":122},"DRUG","LSD tartrate","LSD tartrate equivalent to 25 microgram LSD base",[105],[123],"Lysergic acid diethylamide",{"type":118,"name":111,"description":125,"armGroupLabels":126,"otherNames":16},"Placebo with equal appearance",[111],[128],{"name":129,"affiliation":5,"role":130},"Kees Kramers, Prof.","PRINCIPAL_INVESTIGATOR",[132],{"name":133,"role":134,"phone":135,"phoneExt":16,"email":136},"Julia Jansen, MD","CONTACT","+31 24 3658765","julia.jansen@cwz.nl",[138,160],{"facility":139,"status":140,"city":141,"state":16,"zip":16,"country":142,"countryCode":143,"cosmosGeoPoint":144,"geoPoint":149,"contacts":150},"Leiden University Medical Center (LUMC)","RECRUITING","Leiden","Netherlands","NL",{"type":145,"coordinates":146},"Point",[147,148],4.49306,52.15833,{"lat":148,"lon":147},[151,155,157],{"name":152,"role":134,"phone":153,"phoneExt":16,"email":154},"Martien van Liefland","071 526 21 11","LICIT@LUMC.nl",{"name":156,"role":130,"phone":16,"phoneExt":16,"email":16},"Rolf Fronczek, MD, PhD",{"name":158,"role":159,"phone":16,"phoneExt":16,"email":16},"Martien van Liefland, MD","SUB_INVESTIGATOR",{"facility":161,"status":140,"city":162,"state":16,"zip":16,"country":142,"countryCode":143,"cosmosGeoPoint":163,"geoPoint":167,"contacts":168},"Canisius-Wilhelmina Ziekenhuis (CWZ)","Nijmegen",{"type":145,"coordinates":164},[165,166],5.85278,51.8425,{"lat":166,"lon":165},[169,173,175],{"name":170,"role":134,"phone":171,"phoneExt":16,"email":172},"Julia Jansen","024 365 82 10","LICIT@cwz.nl",{"name":174,"role":130,"phone":16,"phoneExt":16,"email":16},"Willemijn Leen, MD, PhD",{"name":133,"role":159,"phone":16,"phoneExt":16,"email":16},{"type":177,"investigatorFullName":16,"investigatorTitle":16,"investigatorAffiliation":16,"oldNameTitle":16,"oldOrganization":16},"SPONSOR",[179,181,183],{"name":180,"class":6},"ZonMw: The Netherlands Organisation for Health Research and Development",{"name":182,"class":6},"Canisius-Wilhelmina Hospital",{"name":184,"class":6},"Leiden University Medical Center","100475940",false,"NCT05477459","LSD to Improve Cluster Headache Impact Trial","Efficacy and Safety of Minidosing Lysergic Acid Diethylamide (LSD) for Chronic Cluster Headache: a Randomized Placebo-controlled Study","LICIT","Inclusion Criteria:\n\n* CCH according to the International Classification of Headache Disorders version 3 (ICHD-3)\n* At screening: stable weekly attack frequency in the 4 weeks prior to screening (assessed retrospectively), averaging at least 8 per week and each week within a 40% window around the average\n* At randomization: average of at least 8 attacks per week and no absence of attacks on more than two consecutive days during baseline\n\nExclusion Criteria:\n\n* Use of excluded concomitant treatment at screening (lithium; other prophylactics if not on a stable dose for less than one month; steroids\u002FGON block within 2 months before screening; sphenopalatinum block, neurostimulation (changed setting within 3 months before screening) or botulinum toxin within 3 months before screening) and during the double-blind phase\n* Use of LSD(-derivatives) (other than investigational drug), psilocybin, ketamine or cannabis within 3 months prior to screening and throughout the study\n* Lifetime and\u002For family history (first degree relatives) of psychotic or bipolar disorder, suicidal intention or attempt\n* A score of 6 or more on the 'Ervaringenlijst' (PQ-16) to exclude subclinical susceptibility to psychosis\n* Actual abuse of alcohol and\u002For recreational drugs\n* Lifetime history of cardiac valvular disease\n* History or evidence of cognitive disorder at screening\n* Positive urine drug screen at screening\n* Females: Pregnancy, lactation, no acceptable contraceptive use","ALL","16 Years","75 Years",{"count":196,"type":197},65,"ESTIMATED","INTERVENTIONAL",[200],"PHASE2","This study aims to investigate the efficacy and safety of LSD 25μg every 3 days for 3 weeks versus placebo in the treatment of chronic cluster headache (cCH).\n\nIt is a 3-week double-blind placebo-controlled intervention study, preceded by a 4-week baseline observation period and followed by a 5-week post-treatment observation period.\n\nPrimary objective: to evaluate the efficacy of LSD 25μg every 3 days for 3 weeks in cCH.\n\nAdditional objectives:\n\n* To evaluate the safety of LSD 25μg every 3 days for 3 weeks in cCH.\n* To explore the exposure-response relationship of 25μg LSD in cCH.\n* To explore cost-effectiveness of treatment with LSD in cCH.\n* To evaluate the efficacy of LSD on health-related quality of life.",[203],"Chronic Cluster Headache",[205,123],"Chronic cluster headache","2025-04-10",{"date":208,"type":209},"2025-04-15","ACTUAL",{"date":211,"type":197},"2025-04-16",{"date":213,"type":197},"2027-04",{"name":5,"class":6},2]