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Lysergic Acid Diethylamide (LSD) as Treatment for Cluster Headache (LCH)

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ClinicalTrials.gov Identifier: NCT03781128
Recruitment Status : Recruiting
First Posted : December 19, 2018
Last Update Posted : April 20, 2021
Sponsor:
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland

Tracking Information
First Submitted Date  ICMJE November 7, 2018
First Posted Date  ICMJE December 19, 2018
Last Update Posted Date April 20, 2021
Actual Study Start Date  ICMJE January 2, 2019
Estimated Primary Completion Date October 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 18, 2018)
  • Change in frequency of the cluster headache attacks [ Time Frame: 8 weeks before and after pulse regimen ]
    assessed with a standardized headache diary, within-subjects analysis
  • 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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 18, 2018)
  • Episode abortion [ Time Frame: through study completion, an average of 1 year ]
    assessed with a standardized headache diary
  • Change in duration of attacks [ Time Frame: 8 weeks after pulse regimen ]
    assessed with a standardized headache diary
  • Time to first attack after completion of pulse regimen [ Time Frame: 8 weeks after pulse regimen ]
    assessed with a standardized headache diary
  • Cumulative time with headache [ Time Frame: 8 weeks after pulse regimen ]
    assessed with a standardized headache diary
  • Change in cluster period duration and interval between cluster periods [ Time Frame: 8 weeks after pulse regimen ]
    assessed with a standardized headache diary
  • Number of attacks requiring abortive medication [ Time Frame: 8 weeks after pulse regimen ]
    assessed with a standardized headache diary
  • Number of Attack-associated autonomic symptoms [ Time Frame: 8 weeks after pulse regimen ]
    assessed with a standardized headache diary
  • 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
  • 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
  • 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.
  • Acute autonomic effects assessed by blood pressure [ Time Frame: 10 hours after drug administration ]
    systolic and diastolic blood pressure in mmHg
  • Acute autonomic effects assessed by heart rate [ Time Frame: 10 hours after drug administration ]
    heart rate in beats per minute
  • Acute autonomic effects assessed by body temperature [ Time Frame: 10 hours after drug administration ]
    body temperature in °Celsius
  • Adverse Events [ Time Frame: through study completion, an average of 1 year ]
    adverse events will be recorded
  • Acute psychological effects assessed by questionnaire Visual analogue scales (VAS) [ Time Frame: 10 hours after drug administration ]
    assessment of subjective effects using visual analogue scales
  • Acute psychological effects assessed by SCQ [ Time Frame: 10 hours after drug administration ]
    assessed with the states of consciousness questionnaire (SCQ)
  • 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)
  • 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.
  • 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
  • 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
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Lysergic Acid Diethylamide (LSD) as Treatment for Cluster Headache
Official Title  ICMJE Safety and Efficacy of Lysergic Acid Diethylamide (LSD) as Treatment for Cluster Headache: a Randomized, Double-blind, Placebo-controlled Phase II Study
Brief Summary

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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:
Double-blind, randomized, placebo-controlled two-phase cross-over study design.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
double-blind
Primary Purpose: Treatment
Condition  ICMJE Cluster Headache
Intervention  ICMJE
  • Drug: Lysergic Acid Diethylamide
    100 µg, per os, 3 times within 3 weeks
    Other Name: LSD
  • Drug: Placebo
    placebo in an identical-looking vial as LSD, per os, 3 times within 3 weeks
Study Arms  ICMJE
  • LSD, Placebo
    Lysergic acid diethylamide (3 x 100 µg LSD in three weeks, per os) followed by Placebo
    Interventions:
    • Drug: Lysergic Acid Diethylamide
    • Drug: Placebo
  • Placebo, LSD
    Placebo (3 x 1 vial looking like LSD in three weeks, per os) followed by Lysergic acid diethylamide
    Interventions:
    • Drug: Lysergic Acid Diethylamide
    • Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 18, 2018)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2023
Estimated Primary Completion Date October 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 25 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Matthias Liechti, Prof. 0041 61 328 68 68 matthias.liechti@usb.ch
Contact: Yasmin Schmid, Dr. med. 0041 61 328 68 66 yasmin.schmid@usb.ch
Listed Location Countries  ICMJE Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03781128
Other Study ID Numbers  ICMJE BASEC 2018-01082
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University Hospital, Basel, Switzerland
Study Sponsor  ICMJE University Hospital, Basel, Switzerland
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Matthias Liechti University Hospital, Basel, Switzerland
PRS Account University Hospital, Basel, Switzerland
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP