LYSERGIDE (lysergic acid diethylamide, LSD) for Chronic cluster headache

Inclusion criteria

• {"criterion_text":"- 16-75 years of age at screening\n- Diagnosis of chronic cluster headache according to ICHD-3 criteria.\n- At the screening visit, a retrospective assessment of the 4 weeks prior to screening meets all of the following: An average of at least 8 attacks per week; Attack frequency in each week is within a 40% window around the average.\n- At the randomization visit, both of the following are met (inclusion criterion not to be shared with the subject): an average of at least 8 attacks per week; No absence of attacks on more than 2 consecutive days; Attack frequency in each week is within a 40% window around the average\n- Subject has signed informed consent; consent by proxy is not allowed.\n- Subject is aware of and willing to conform to all study procedures and visits.\n- Subjects are on a stable regimen of cluster headache prophylactics (defined in table 1 of study protocol) and agree not to increase the dose nor start a new cluster prophylactic during the screening and double-blind phase of the study.\n- Women of child-bearing potential must test negative for pregnancy at screening and start of treatment.\n- All females must agree either to abstain from sexual intercourse with a male partner, or to use of a reliable method of birth control during screening and treatment period as well as for 1 week after the last dose of study drug. Acceptable methods of birth control for this study include: oral contraceptives; implantable contraceptives; injectable contraceptives; a contraceptive patch; barrier methods such as diaphragms with contraceptive jelly, cervical caps with contraceptive jelly, condoms with contraceptive foam, or intrauterine devices; or a partner with vasectomy. Birth control is not required if the female is infertile due to surgical sterilization (hysterectomy, or at least 6 weeks after surgical bilateral oophorectomy or tubal ligation) confirmed by medical history or menopause. Menopause is defined as spontaneous amenorrhea for at least 12 months not induced by a medical condition."}

Exclusion criteria

• {"criterion_text":"- Known or suspected structural cause for cluster headache attacks (cluster-mimics).\n- Positive drug screen at screening.\n- History of cardiac valvular disease or disorder.\n- History or evidence of cognitive disorder at screening; MOCA <26 at screening.\n- History of significant and active medical comorbidities, including but not limited to hepatic, renal, urethral, vascular or cardiac valvular disease, cardiac rhythm disorders and hypertension (according to professional judgement).\n- Women who are pregnant or nursing.\n- Blood pressure at screening >160/100; pulse rate at screening >100 beats per minute.\n- eGFR at screening <60 ml/min.\n- Other headaches, if the patient cannot reliably distinguish them from attacks of cluster headache.\n- Current use of any of the prohibited prophylactic cluster headache treatments (defined in study protocol table 1), unless used under de conditions described in table 1 of the study protocol.\n- History of or actual psychotic or bipolar disorder; first degree relative(s) with (a history of) psychotic or bipolar disorder\n- A score of 6 or more on the ‘Ervaringenlijst’ (PQ-16).\n- History of suicidal intention or attempt and/or first degree relative with known history of suicidal intention or attempt.\n- The subject is at significant risk of suicide (at the at the discretion of the investigator or when in the C-SSRS a subject answers ‘yes’ to suicidal ideation questions 4 or 5 or to suicidal behaviour).\n- Active abuse of alcohol and/or any current use or severe past abuse of Schedule I listed drugs (Dutch: lijst 1 van de Opiumwet), at the discretion of the investigator (based on type of drug, reason for abuse (medical or non-medical), duration of abuse and abstinence, professional, relational and social impact, amongst others).\n- Medicinal or recreational use of cannabis, if any of the following applies: a score of ≥8 on the CUDIT-R is attained OR cannabis use within the 6 weeks prior to screening OR abstinence from using cannabis is refused for the duration of the study"}

Primary endpoints

• {"endpoint_text":"- Mean change in weekly attack frequency in the third treatment week compared to the 4-week baseline, across treatment groups.","definition_or_measurement_approach":"Mean change in weekly attack frequency in the third treatment week compared to the 4-week baseline, across treatment groups (i.e. comparison of mean weekly attack frequency in week 3 of treatment vs 4-week baseline period)."}

Netherlands

Earliest CTIS Part Ii Submission Date

21-01-2025

Latest Decision Or Authorization Date

06-03-2026

Processing Time Days

409

Number Of Sites

3

Number Of Participants

52

Primary sponsor

Full Name

Radboud universitair medisch centrum Stichting

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands