LSD to Improve Cluster Headache Impact Trial

NCT05477459 | Recruiting Phase 2 DMC

• 1 other identifier: 131-2022
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 2

Brief Summary

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). It 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. Primary objective: to evaluate the efficacy of LSD 25μg every 3 days for 3 weeks in cCH. Additional objectives:

• To evaluate the safety of LSD 25μg every 3 days for 3 weeks in cCH.
• To explore the exposure-response relationship of 25μg LSD in cCH.
• To explore cost-effectiveness of treatment with LSD in cCH.
• To evaluate the efficacy of LSD on health-related quality of life.

Conditions

Chronic Cluster Headache

Keywords

Chronic cluster headache; Lysergic acid diethylamide

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (22)

• Mean change in weekly attack frequency across weeks 4-8 compared to the 4-week baseline and for each week separately.

  week 8 post-randomization

• 100% reduction (remission rate) in number of weekly attacks in the third treatment week, compared to the 4-week baseline, across treatment groups.

  week 3 post-randomization

• ≥50% reduction (50% responder rate) in number of weekly attacks in the third treatment week, compared to the 4-week baseline, across treatment groups.

  week 3 post-randomization

• ≥30% reduction (30% responder rate) in number of weekly attacks in the third treatment week, compared to the 4-week baseline, across treatment groups.

  week 3 post-randomization

• 100% reduction (remission rate) in number of weekly attacks across weeks 4-8 compared to the 4-week baseline and for each week separately.

  week 8 post-randomization

Other Outcomes (2)

• Alcohol consumption

  during the entire 12-week duration of the study

• PK-PD modelling

  Week 1 and 3

Study Arms (2)

Verum

EXPERIMENTAL

Lysergic diethylamide tartrate (equivalent to 25 microgram LSD base), one dose every 3 days for 3 weeks (totalling 7 vials)

Drug: LSD tartrate

Placebo

PLACEBO COMPARATOR

Placebo vial looking like verum vial, one vial every 3 days for 3 weeks (totalling 7 vials)

Drug: Placebo

Interventions

LSD tartrate DRUG

LSD tartrate equivalent to 25 microgram LSD base

Also known as: Lysergic acid diethylamide

Verum

Placebo DRUG

Placebo with equal appearance

Placebo

Eligibility Criteria

• Age: 16 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• CCH according to the International Classification of Headache Disorders version 3 (ICHD-3)
• 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
• At randomization: average of at least 8 attacks per week and no absence of attacks on more than two consecutive days during baseline

You may not qualify if:

• Use of excluded concomitant treatment at screening (lithium; other prophylactics if not on a stable dose for less than one month; steroids/GON 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
• Use of LSD(-derivatives) (other than investigational drug), psilocybin, ketamine or cannabis within 3 months prior to screening and throughout the study
• Lifetime and/or family history (first degree relatives) of psychotic or bipolar disorder, suicidal intention or attempt
• A score of 6 or more on the 'Ervaringenlijst' (PQ-16) to exclude subclinical susceptibility to psychosis
• Actual abuse of alcohol and/or recreational drugs
• Lifetime history of cardiac valvular disease
• History or evidence of cognitive disorder at screening
• Positive urine drug screen at screening
• Females: Pregnancy, lactation, no acceptable contraceptive use

Sponsors & Collaborators

• Radboud University Medical Center: lead
• ZonMw: The Netherlands Organisation for Health Research and Development: collaborator
• Canisius-Wilhelmina Hospital: collaborator
• Leiden University Medical Center: collaborator

Study Sites (2)

Leiden University Medical Center (LUMC)

Leiden, Netherlands

RECRUITING

Canisius-Wilhelmina Ziekenhuis (CWZ)

Nijmegen, Netherlands

RECRUITING

Related Publications (8)

• Hoffmann J, May A. Diagnosis, pathophysiology, and management of cluster headache. Lancet Neurol. 2018 Jan;17(1):75-83. doi: 10.1016/S1474-4422(17)30405-2. Epub 2017 Nov 23.

  PMID: 29174963 BACKGROUND

• Rozen TD, Fishman RS. Cluster headache in the United States of America: demographics, clinical characteristics, triggers, suicidality, and personal burden. Headache. 2012 Jan;52(1):99-113. doi: 10.1111/j.1526-4610.2011.02028.x. Epub 2011 Nov 11.

  PMID: 22077141 BACKGROUND

• Tepper SJ, Stillman MJ. Cluster headache: potential options for medically refractory patients (when all else fails). Headache. 2013 Jul-Aug;53(7):1183-90. doi: 10.1111/head.12148. Epub 2013 Jun 28.

  PMID: 23808603 BACKGROUND

• McGeeney BE. Cannabinoids and hallucinogens for headache. Headache. 2013 Mar;53(3):447-58. doi: 10.1111/head.12025. Epub 2012 Dec 20.

  PMID: 23278122 BACKGROUND

• Andersson M, Persson M, Kjellgren A. Psychoactive substances as a last resort-a qualitative study of self-treatment of migraine and cluster headaches. Harm Reduct J. 2017 Sep 5;14(1):60. doi: 10.1186/s12954-017-0186-6.

  PMID: 28870224 BACKGROUND

• Sewell RA, Halpern JH, Pope HG Jr. Response of cluster headache to psilocybin and LSD. Neurology. 2006 Jun 27;66(12):1920-2. doi: 10.1212/01.wnl.0000219761.05466.43.

  PMID: 16801660 BACKGROUND

• Schindler EA, Gottschalk CH, Weil MJ, Shapiro RE, Wright DA, Sewell RA. Indoleamine Hallucinogens in Cluster Headache: Results of the Clusterbusters Medication Use Survey. J Psychoactive Drugs. 2015 Nov-Dec;47(5):372-81. doi: 10.1080/02791072.2015.1107664. Epub 2015 Nov 23.

  PMID: 26595349 BACKGROUND

• de Coo IF, Naber WC, Wilbrink LA, Haan J, Ferrari MD, Fronczek R. Increased use of illicit drugs in a Dutch cluster headache population. Cephalalgia. 2019 Apr;39(5):626-634. doi: 10.1177/0333102418804160. Epub 2018 Oct 5.

  PMID: 30290701 BACKGROUND

MeSH Terms

Conditions

Cluster Headache

Interventions

Lysergic Acid Diethylamide

Condition Hierarchy (Ancestors)

Trigeminal Autonomic Cephalalgias; Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Lysergic Acid; Ergolines; Ergot Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring

Study Officials

• Kees Kramers, Prof.

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Julia Jansen, MD

CONTACT

+31 24 3658765; julia.jansen@cwz.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Study drug or placebo are similar in appearance, taste and smell
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: July 5, 2022
• First Posted: July 28, 2022
• Study Start: April 16, 2025
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: April 15, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: 9-36 months after article publication
• Access Criteria: For purpose of meta-analysis and approved by an independent review board

Locations

NL (2)