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Psilocybin for the Treatment of Cluster Headache

Primary Purpose

Cluster Headache

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
0.143 mg/kg Psilocybin or 10 mg Psilocybin
0.0143 mg/kg Psilocybin or 1 mg Psilocybin
Placebo
Sponsored by
Yale University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cluster Headache

Eligibility Criteria

21 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Chronic cluster headache with at least one attack daily
  • Episodic cluster headache with periods that are predictable and have a duration of approximately 2 months
  • Attacks are managed by means involving no more than twice weekly triptan use (e.g., high-flow oxygen, heat/cold pack)

Exclusion Criteria:

  • Axis I psychotic disorder (e.g. schizophrenia, bipolar I, depression with psychosis)
  • Axis I psychotic disorder in first degree relative
  • Unstable medical condition, severe renal, cardiac or hepatic disease, pacemaker, or serious central nervous system pathology
  • Pregnant, breastfeeding, lack of adequate birth control
  • History of intolerance to psilocybin, lysergic acid diethylamide (LSD), or related compounds
  • Drug or alcohol abuse within the past 3 months (excluding tobacco)
  • Urine toxicology positive to drugs of abuse
  • Use of vasoconstrictive medications (i.e. sumatriptan, pseudoephedrine, midodrine) within five half-lives of test days
  • Use of serotonergic antiemetics (i.e. ondansetron) in the past 2 weeks
  • Use of antidepressant medications (i.e. amitriptyline, isocarboxazid, fluoxetine, citalopram) in the past 6 weeks
  • Use of steroids or certain other immunomodulatory agents (i.e. azathioprine) in the past 2 weeks

Sites / Locations

  • VA Connecticut Healthcare System

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Placebo Comparator

Arm Label

Psilocybin High Dose

Psilocybin Low Dose

Placebo

Arm Description

Outcomes

Primary Outcome Measures

Time to first attack after completion of pulse regimen
Measured in days
Time to last attack after completion of pulse regimen
Measured in days
Change in frequency of attacks
Average number of attacks (number per week)
Change in intensity of attacks
Average intensity of attacks (1-10 on visual analog scale)
Change in duration of attacks
Average duration of attacks (minutes)
Change in cluster period duration compared to typical cluster period (episodic subjects only)
Duration of cluster period after intervention (days)
Difference in the change in cluster attack frequency between 1st and 2nd round
Average number of attacks (number per week); only in those subjects who return for 2nd round
Difference in the change in cluster attack intensity between 1st and 2nd round
Average intensity of attacks (1-10 on visual analog scale); only in those subjects who return for 2nd round
Difference in the change in the duration of attacks between 1st and 2nd round
Average duration of attacks (minutes); only in those subjects who return for 2nd round

Secondary Outcome Measures

Use of abortive/rescue medication
Number of times per week
Attack-free time
Number of 24 hour days (may be nonconsecutive)
Health-Related Quality of life
Using the CDC's Health-Related Quality of Life (HRQOL) scale
Psychedelic effects
Using the 5-Dimensional Altered States of Consciousness (5D-ASC) scale
Change in blood pressure
Maximum change from baseline during each experimental session (mmHg)
Change in heart rate
Maximum change from baseline during each experimental session (beats per minute)
Change in peripheral oxygenation
Maximum change from baseline during each experimental session (SpO2)

Full Information

First Posted
November 11, 2016
Last Updated
June 13, 2023
Sponsor
Yale University
Collaborators
Heffter Research Institute, Ceruvia Lifesciences
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1. Study Identification

Unique Protocol Identification Number
NCT02981173
Brief Title
Psilocybin for the Treatment of Cluster Headache
Official Title
Safety and Efficacy of Psilocybin for the Treatment of Headache Disorders
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 2016 (undefined)
Primary Completion Date
June 30, 2022 (Actual)
Study Completion Date
September 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Yale University
Collaborators
Heffter Research Institute, Ceruvia Lifesciences

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to investigate the effects of an oral psilocybin pulse regimen in cluster headache. Subjects will be randomized to receive oral placebo, low dose psilocybin, or high dose psilocybin in three experimental sessions, each separated by 5 days. Subjects will maintain a headache diary prior to, during, and after the pulse regimen in order to document headache frequency and intensity before, during, and after the pulse regimen. After at least 6 months from the last experimental session, subjects may be invited for a second round, in which they will be randomized to receive either low dose or high dose psilocybin.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cluster Headache

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Psilocybin High Dose
Arm Type
Active Comparator
Arm Title
Psilocybin Low Dose
Arm Type
Active Comparator
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
0.143 mg/kg Psilocybin or 10 mg Psilocybin
Intervention Description
0.143 mg/kg psilocybin capsule (weight-based option) or 10 mg psilocybin capsule (fixed-dose option) ingested on each of three test days (5 days apart +/- 1-2 days)
Intervention Type
Drug
Intervention Name(s)
0.0143 mg/kg Psilocybin or 1 mg Psilocybin
Intervention Description
0.0143 mg/kg psilocybin capsule (weight-based option) or 1 mg psilocybin (fixed-dose option) ingested on each of three test days (5 days apart +/- 1-2 days)
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Microcrystalline cellulose capsule ingested on each of three test days (5 days apart +/- 1-2 days)
Primary Outcome Measure Information:
Title
Time to first attack after completion of pulse regimen
Description
Measured in days
Time Frame
Two months following the completion of pulse regimen (after completion of experimental sessions 1, 2, and 3)
Title
Time to last attack after completion of pulse regimen
Description
Measured in days
Time Frame
Six months following the completion of pulse regimen (after completion of experimental sessions 1, 2, and 3)
Title
Change in frequency of attacks
Description
Average number of attacks (number per week)
Time Frame
Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary
Title
Change in intensity of attacks
Description
Average intensity of attacks (1-10 on visual analog scale)
Time Frame
Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary
Title
Change in duration of attacks
Description
Average duration of attacks (minutes)
Time Frame
Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary
Title
Change in cluster period duration compared to typical cluster period (episodic subjects only)
Description
Duration of cluster period after intervention (days)
Time Frame
Measured from 2 weeks before pulse regimen to 6 months following the completion of pulse regimen, then comparing to historical average duration of cluster periods
Title
Difference in the change in cluster attack frequency between 1st and 2nd round
Description
Average number of attacks (number per week); only in those subjects who return for 2nd round
Time Frame
Measured from 2 weeks before to 2 months after completion for each of the two pulse regimens using a headache diary
Title
Difference in the change in cluster attack intensity between 1st and 2nd round
Description
Average intensity of attacks (1-10 on visual analog scale); only in those subjects who return for 2nd round
Time Frame
Measured from 2 weeks before to 2 months after completion for each of the two pulse regimens using a headache diary
Title
Difference in the change in the duration of attacks between 1st and 2nd round
Description
Average duration of attacks (minutes); only in those subjects who return for 2nd round
Time Frame
Measured from 2 weeks before to 2 months after completion for each of the two pulse regimens using a headache diary
Secondary Outcome Measure Information:
Title
Use of abortive/rescue medication
Description
Number of times per week
Time Frame
Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary
Title
Attack-free time
Description
Number of 24 hour days (may be nonconsecutive)
Time Frame
Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary
Title
Health-Related Quality of life
Description
Using the CDC's Health-Related Quality of Life (HRQOL) scale
Time Frame
Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary
Title
Psychedelic effects
Description
Using the 5-Dimensional Altered States of Consciousness (5D-ASC) scale
Time Frame
Taken daily on each experimental day after the resolution of psychedelic effects, approximately 6 hours after drug administration
Title
Change in blood pressure
Description
Maximum change from baseline during each experimental session (mmHg)
Time Frame
Measured during each experimental session prior to drug administration, every 15 min in the first hour after drug administration, every 30 min in the second hour, and then hourly for 4 hours or until resolution of psychedelic effects (~6 hours post drug)
Title
Change in heart rate
Description
Maximum change from baseline during each experimental session (beats per minute)
Time Frame
Measured during each experimental session prior to drug administration, every 15 min in the first hour after drug administration, every 30 min in the second hour, and then hourly for 4 hours or until resolution of psychedelic effects (~6 hours post drug)
Title
Change in peripheral oxygenation
Description
Maximum change from baseline during each experimental session (SpO2)
Time Frame
Measured during each experimental session prior to drug administration, every 15 min in the first hour after drug administration, every 30 min in the second hour, and then hourly for 4 hours or until resolution of psychedelic effects (~6 hours post drug)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Chronic cluster headache with at least one attack daily Episodic cluster headache with periods that are predictable and have a duration of approximately 2 months Attacks are managed by means involving no more than twice weekly triptan use (e.g., high-flow oxygen, heat/cold pack) Exclusion Criteria: Axis I psychotic disorder (e.g. schizophrenia, bipolar I, depression with psychosis) Axis I psychotic disorder in first degree relative Unstable medical condition, severe renal, cardiac or hepatic disease, pacemaker, or serious central nervous system pathology Pregnant, breastfeeding, lack of adequate birth control History of intolerance to psilocybin, lysergic acid diethylamide (LSD), or related compounds Drug or alcohol abuse within the past 3 months (excluding tobacco) Urine toxicology positive to drugs of abuse Use of vasoconstrictive medications (i.e. sumatriptan, pseudoephedrine, midodrine) within five half-lives of test days Use of serotonergic antiemetics (i.e. ondansetron) in the past 2 weeks Use of antidepressant medications (i.e. amitriptyline, isocarboxazid, fluoxetine, citalopram) in the past 6 weeks Use of steroids or certain other immunomodulatory agents (i.e. azathioprine) in the past 2 weeks
Facility Information:
Facility Name
VA Connecticut Healthcare System
City
West Haven
State/Province
Connecticut
ZIP/Postal Code
06516
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Psilocybin for the Treatment of Cluster Headache

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