- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03781128
Lysergic Acid Diethylamide (LSD) as Treatment for Cluster Headache (LCH)
Safety and Efficacy of Lysergic Acid Diethylamide (LSD) as Treatment for Cluster Headache: a Randomized, Double-blind, Placebo-controlled Phase II Study
Background: After no official research in humans in the last 40 years, research and therapeutic uses of the serotonergic psychedelic lysergic acid diethylamide (LSD) are now re-recognized and include its use in brain research, alcoholism, anxiety associated with terminal illness, and treatment of headache disorders. Specifically, LSD has been reported to abort attacks, to decrease frequency and intensity of attacks, and to induce remission in patients suffering from cluster headache (CH).
Objective: To investigate the effects of an oral LSD pulse regimen (3 x 100 µg LSD in three weeks) in patients suffering from CH compared with placebo.
Design: Double-blind, randomized, placebo-controlled two-phase cross-over study design.
Participants: 30 patients aged ≥ 25 and ≤ 75 years with chronic or episodic CH with predictable periods lasting approximately 2 months and attacks responding to oxygen.
Main outcome measures: Changes in frequency and intensity of CH attacks assessed with a standardized headache diary Significance: CH is often rated as the most painful of all primary headaches, which not only causes significant disability, but is also associated with enormous personal, economic, and psychiatric burden. At the moment, there is no specific treatment available for CH, but serotonergic compounds represent an important drug class, especially in the abortive management of cluster attacks. However, there is a need for new treatment approaches, as CH is also often insufficiently managed with available medication. This study will evaluate the potential benefit and safety of a treatment with LSD for patients with CH.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Matthias Liechti, Prof.
- Phone Number: 0041 61 328 68 68
- Email: matthias.liechti@usb.ch
Study Contact Backup
- Name: Yasmin Schmid, Dr. med.
- Phone Number: 0041 61 328 68 66
- Email: yasmin.schmid@usb.ch
Study Locations
-
-
-
Basel, Switzerland, 4031
- Recruiting
- Clinical Pharmacology & Toxicology, University Hospital Basel
-
Contact:
- Matthias Liechti, Prof.
- Phone Number: +41 61 328 68 68
- Email: matthias.liechti@usb.ch
-
Contact:
- Yasmin Schmid, Dr. med.
- Phone Number: +41 61 328 68 66
- Email: yasmin.schmid@usb.ch
-
Principal Investigator:
- Matthias Liechti, Prof.
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Age ≥ 25 and ≤ 75 years
- Chronic cluster headache (according to the International Headache Society (IHS) criteria) OR
- Episodic cluster headache (according to the IHS criteria) with recurrent predictable episodes lasting approximately 2 months and expected ongoing cluster period for at least one month beyond the inclusion
- Attacks respond to oxygen
- Sufficient understanding of the study procedures and risks associated with the study
- Participants must be willing to adhere to the study procedures and sign the consent form
- Participants are willing to abstain from taking preventive and abortive medication (except from oxygen) long enough before and after the LSD/placebo treatment session to avoid the possibility of a drug-drug interaction
- Participants are willing to refrain from taking any psychiatric medications during the experimental session period. If they are being treated with antidepressants, lithium or are taking anxiolytic medications on a fixed daily regimen, such drugs must be discontinued long enough before the LSD/placebo treatment session to avoid the possibility of a drug-drug interaction.
- Participants must also refrain from the use of any psychoactive drugs and caffeine within 24 hours of each LSD/placebo treatment session. They must agree not to use nicotine for at least 2 hours before and 6 hours after each dose of LSD. They must agree to not ingest alcohol-containing beverages for at least 1 day before each LSD treatment session. Non-routine medications for treating breakthrough pain taken in the 24 hours before the LSD treatment session may result in rescheduling the treatment session to another date, with the decision at the discretion of the investigators after discussion with the participant.
- Participants must be willing not to drive a traffic vehicle or to operate machines within 24 hours after LSD/placebo administration.
Exclusion Criteria:
- Other forms of headache attacks (migraine, paroxysmal hemicranias, shortlasting unilateral neuralgiform headache attacks with conjunctival injection, tearing, sweating and rhinorrhea (SUNCT) or with cranial autonomic symptoms (SUNA))
- Women who are pregnant, nursing or of child-bearing potential and are not practicing an effective means of birth control (double-barrier method, i.e. pill/intrauterine device and preservative/diaphragm)
- Past or present diagnosis of a primary psychotic disorder. Subjects with a first degree relative with psychotic disorders are also excluded.
- Past or present bipolar disorder (DSM-IV).
- Current substance use disorder (within the last 2 months, DSM-V, except nicotine).
- Somatic disorders including severe cardiovascular disease, untreated hypertension (systolic blood pressure > 160mmHg without treatment, systolic blood pressure > 140 mmHg with treatment), severe liver disease (liver enzymes increase by more than 5 times the upper limit of normal) or severely impaired renal function (estimated creatinine clearance <30 ml/min), or other that in the judgement of the investigators pose too great potential for side effects.
- Weight < 45kg
- Participation in another clinical trial (currently or within the last 30 days)
- Participants taking higher steroid doses (>10mg/d) over a longer time period (>2 weeks), as this would require tapering
- Use of immunomodulatory agents (i.e. azathioprine) in the past 2 weeks
- Use of serotonergic antiemetics (i.e. ondansetron) in the past 2 weeks
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: LSD, Placebo
Lysergic acid diethylamide (3 x 100 µg LSD in three weeks, per os) followed by Placebo
|
100 µg, per os, 3 times within 3 weeks
Other Names:
placebo in an identical-looking vial as LSD, per os, 3 times within 3 weeks
|
Other: Placebo, LSD
Placebo (3 x 1 vial looking like LSD in three weeks, per os) followed by Lysergic acid diethylamide
|
100 µg, per os, 3 times within 3 weeks
Other Names:
placebo in an identical-looking vial as LSD, per os, 3 times within 3 weeks
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in frequency of the cluster headache attacks
Time Frame: 8 weeks before and after pulse regimen
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assessed with a standardized headache diary, within-subjects analysis
|
8 weeks before and after pulse regimen
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Change in intensity of the cluster headache attacks
Time Frame: 8 weeks before and after pulse regimen
|
assessed with a standardized headache diary, within-subjects analysis
|
8 weeks before and after pulse regimen
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Episode abortion
Time Frame: through study completion, an average of 1 year
|
assessed with a standardized headache diary
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through study completion, an average of 1 year
|
Change in duration of attacks
Time Frame: 8 weeks after pulse regimen
|
assessed with a standardized headache diary
|
8 weeks after pulse regimen
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Time to first attack after completion of pulse regimen
Time Frame: 8 weeks after pulse regimen
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assessed with a standardized headache diary
|
8 weeks after pulse regimen
|
Cumulative time with headache
Time Frame: 8 weeks after pulse regimen
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assessed with a standardized headache diary
|
8 weeks after pulse regimen
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Change in cluster period duration and interval between cluster periods
Time Frame: 8 weeks after pulse regimen
|
assessed with a standardized headache diary
|
8 weeks after pulse regimen
|
Number of attacks requiring abortive medication
Time Frame: 8 weeks after pulse regimen
|
assessed with a standardized headache diary
|
8 weeks after pulse regimen
|
Number of Attack-associated autonomic symptoms
Time Frame: 8 weeks after pulse regimen
|
assessed with a standardized headache diary
|
8 weeks after pulse regimen
|
Quality of life assessed by questionnaires: 36-item short-form health survey (SF-36)
Time Frame: through study completion, an average of 1 year
|
assessment with the validated 36-item short-form health survey (SF-36), which measures health-related quality of life
|
through study completion, an average of 1 year
|
Quality of life assessed by questionnaires: 5-level EuroQoL-5D (EQ-5D-5L)
Time Frame: through study completion, an average of 1 year
|
assessment with the 5-level EuroQoL-5D (EQ-5D-5L), which is a standardized instrument developed by the EuroQol Group as a measure of health-related quality of life
|
through study completion, an average of 1 year
|
Quality of life assessed by questionnaires: Headache Impact Test (HIT-6)
Time Frame: through study completion, an average of 1 year
|
assessment with the Headache Impact Test (HIT-6), which measures the adverse impact of headache on social functioning, role functioning, vitality, cognitive functioning and psychological distress.
|
through study completion, an average of 1 year
|
Acute autonomic effects assessed by blood pressure
Time Frame: 10 hours after drug administration
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systolic and diastolic blood pressure in mmHg
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10 hours after drug administration
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Acute autonomic effects assessed by heart rate
Time Frame: 10 hours after drug administration
|
heart rate in beats per minute
|
10 hours after drug administration
|
Acute autonomic effects assessed by body temperature
Time Frame: 10 hours after drug administration
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body temperature in °Celsius
|
10 hours after drug administration
|
Adverse Events
Time Frame: through study completion, an average of 1 year
|
adverse events will be recorded
|
through study completion, an average of 1 year
|
Acute psychological effects assessed by questionnaire Visual analogue scales (VAS)
Time Frame: 10 hours after drug administration
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assessment of subjective effects using visual analogue scales
|
10 hours after drug administration
|
Acute psychological effects assessed by SCQ
Time Frame: 10 hours after drug administration
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assessed with the states of consciousness questionnaire (SCQ)
|
10 hours after drug administration
|
Acute psychological effects assessed by questionnaire 5-dimensions of altered states of consciousness
Time Frame: 10 hours after drug administration
|
assessed with the 5-dimensions of altered states of consciousness questionnaire (5D-ASC)
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10 hours after drug administration
|
Persisting effects attributed to the LSD experience
Time Frame: through study completion, an average of 1 year
|
assessment of persisting effects with the persisting effects questionnaire (PEQ) which assesses changes in attitude, mood, behavior and spiritual experience.
The questionnaire will be completed at the beginning, after pulse regimens, and at the end of the study.
|
through study completion, an average of 1 year
|
Change of attack frequency at the end of the study compared with baseline
Time Frame: through study completion, an average of 1 year
|
pre-post study comparison in all subjects, assessed with a standardized headache diary
|
through study completion, an average of 1 year
|
Change of attack intensity at the end of the study compared with baseline
Time Frame: through study completion, an average of 1 year
|
pre-post study comparison in all subjects, assessed with a standardized headache diary
|
through study completion, an average of 1 year
|
Change in attack frequency before and after pulse regimen
Time Frame: 8 weeks after first pulse regimen
|
between-subjects analysis before cross-over, assessed with a standardized headache diary
|
8 weeks after first pulse regimen
|
Change in attack intensity before and after pulse regimen
Time Frame: 8 weeks after first pulse regimen
|
between-subjects analysis before cross-over, assessed with a standardized headache diary
|
8 weeks after first pulse regimen
|
Effects on depressive /anxious symptoms assessed by questionnaires: State-trait anxiety inventory (STAI)
Time Frame: through study completion, an average of 1 year
|
assessment with the State-trait anxiety inventory (STAI), which measures anxiety
|
through study completion, an average of 1 year
|
Effects on depressive /anxious symptoms assessed by questionnaires: Generalized anxiety disorder-7 (GAD-7)
Time Frame: through study completion, an average of 1 year
|
assessment with the Generalized anxiety disorder (GAD-7), which measures anxiety
|
through study completion, an average of 1 year
|
Effects on depressive /anxious symptoms assessed by questionnaires: Hospital Anxiety and Depression Scale (HADS)
Time Frame: through study completion, an average of 1 year
|
assessment with the Hospital Anxiety and Depression Scale (HADS), which measures anxiety and depression severity
|
through study completion, an average of 1 year
|
Effects on depressive /anxious symptoms assessed by questionnaires: Beck Depression Inventory (BDI)
Time Frame: through study completion, an average of 1 year
|
assessment with the Beck Depression Inventory (BDI), which measures depression
|
through study completion, an average of 1 year
|
Effects on depressive /anxious symptoms assessed by questionnaires: Patient health questionnaire-9 (PHQ-9)
Time Frame: through study completion, an average of 1 year
|
assessment with the Patient health questionnaire-9 (PHQ-9), which measures depression
|
through study completion, an average of 1 year
|
Blinding
Time Frame: after study days and at the end of study visit
|
patients and investigators will be asked at the end of a study day and and the end of the study visit to guess the drug treatment
|
after study days and at the end of study visit
|
Expectancy
Time Frame: at screening
|
a modified 2-item version of the Credibility / Expectancy Questionnaire (CEQ) will be used
|
at screening
|
Collaborators and Investigators
Investigators
- Principal Investigator: Matthias Liechti, University Hospital, Basel, Switzerland
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Pain
- Neurologic Manifestations
- Headache Disorders, Primary
- Headache Disorders
- Trigeminal Autonomic Cephalalgias
- Headache
- Cluster Headache
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Psychotropic Drugs
- Serotonin Agents
- Serotonin Receptor Agonists
- Serotonin Antagonists
- Hallucinogens
- Lysergic Acid Diethylamide
Other Study ID Numbers
- BASEC 2018-01082
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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