Efficacy and safety of minidosing lysergic acid diethylamide (LSD) for chronic cluster headache: a randomized placebo-controlled study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Radboud universitair medisch centrum Stichting

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

1 Apr 2025 → ongoing

Decision date (initial)

2025-01-21

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-520305-39-00

EudraCT number

2022-003272-16

ClinicalTrials.gov

NCT05477459

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the efficacy and safety of LSD 25μg every 3 days for 3 weeks in chronic cluster headache.

Conditions and MedDRA coding

Chronic cluster headache

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 16-75 years of age at screening
2. Diagnosis of chronic cluster headache according to ICHD-3 criteria.
3. 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.
4. 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
5. Subject has signed informed consent; consent by proxy is not allowed.
6. Subject is aware of and willing to conform to all study procedures and visits.
7. 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.
8. Women of child-bearing potential must test negative for pregnancy at screening and start of treatment.
9. 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 16

1. Known or suspected structural cause for cluster headache attacks (cluster-mimics).
2. Other headaches, if the patient cannot reliably distinguish them from attacks of cluster headache.
3. 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.
4. History of or actual psychotic or bipolar disorder; first degree relative(s) with (a history of) psychotic or bipolar disorder
5. A score of 6 or more on the ‘Ervaringenlijst’ (PQ-16).
6. History of suicidal intention or attempt and/or first degree relative with known history of suicidal intention or attempt.
7. 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).
8. 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).
9. 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
10. Positive drug screen at screening.
11. History of cardiac valvular disease or disorder.
12. History or evidence of cognitive disorder at screening; MOCA <26 at screening.
13. 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).
14. Women who are pregnant or nursing.
15. Blood pressure at screening >160/100; pulse rate at screening >100 beats per minute.
16. eGFR at screening <60 ml/min.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Mean change in weekly attack frequency in the third treatment week compared to the 4-week baseline, across treatment groups.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Radboud universitair medisch centrum Stichting

Sponsor organisation

Radboud universitair medisch centrum Stichting

Address

Geert Grooteplein Zuid 10

City

Nijmegen

Postcode

6525 GA

Country

Netherlands

Scientific contact point

Organisation

Radboud universitair medisch centrum Stichting

Contact name

Prof. dr. Kees Kramers

Public contact point

Organisation

Radboud universitair medisch centrum Stichting

Contact name

Prof. dr. Kees Kramers

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications