Psilocybin for the Treatment of Cluster Headache

• ClinicalTrials.gov Identifier: NCT02981173
• Recruitment Status: Recruiting
• First Posted: December 5, 2016
• Last Update Posted: January 8, 2021
• Sponsor: Yale University
• Collaborators: Heffter Research Institute; Cluster Headache-Trigeminal Autonomic Cephalalgia (CH-TAC), LLC
• Information provided by (Responsible Party): Deepak C. D'Souza, Yale University

Tracking Information

• First Submitted Date: November 11, 2016
• First Posted Date: December 5, 2016
• Last Update Posted Date: January 8, 2021
• Study Start Date: November 2016
• Estimated Primary Completion Date: June 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 14, 2020)

• Time to first attack after completion of pulse regimen [ Time Frame: Two months following the completion of pulse regimen (after completion of experimental sessions 1, 2, and 3) ]
  Measured in days
• Time to last attack after completion of pulse regimen [ Time Frame: Six months following the completion of pulse regimen (after completion of experimental sessions 1, 2, and 3) ]
  Measured in days
• Change in frequency of attacks [ Time Frame: Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary ]
  Average number of attacks (number per week)
• Change in intensity of attacks [ Time Frame: Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary ]
  Average intensity of attacks (1-10 on visual analog scale)
• Change in duration of attacks [ Time Frame: Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary ]
  Average duration of attacks (minutes)
• Change in cluster period duration compared to typical cluster period (episodic subjects only) [ 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 ]
  Duration of cluster period after intervention (days)
• Difference in the change in cluster attack frequency between 1st and 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 ]
  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 [ Time Frame: Measured from 2 weeks before to 2 months after completion for each of the two pulse regimens using a headache diary ]
  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 [ Time Frame: Measured from 2 weeks before to 2 months after completion for each of the two pulse regimens using a headache diary ]
  Average duration of attacks (minutes); only in those subjects who return for 2nd round

Original Primary Outcome Measures (submitted: November 30, 2016)

• Time to first attack after completion of pulse regimen [ Time Frame: Two months following the completion of pulse regimen (after completion of experimental sessions 1, 2, and 3) ]
  Measured in days
• Change in frequency of attacks [ Time Frame: Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary ]
  Average number of attacks (number per week)
• Change in intensity of attacks [ Time Frame: Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary ]
  Average intensity of attacks (1-10 on visual analog scale)
• Change in duration of attacks [ Time Frame: Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary ]
  Average duration of attacks (minutes)

Current Secondary Outcome Measures (submitted: December 18, 2018)

• Use of abortive/rescue medication [ Time Frame: Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary ]
  Number of times per week
• Attack-free time [ Time Frame: Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary ]
  Number of 24 hour days (may be nonconsecutive)
• Health-Related Quality of life [ Time Frame: Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary ]
  Using the CDC's Health-Related Quality of Life (HRQOL) scale
• Psychedelic effects [ Time Frame: Taken daily on each experimental day after the resolution of psychedelic effects, approximately 6 hours after drug administration ]
  Using the 5-Dimensional Altered States of Consciousness (5D-ASC) scale
• Change in blood pressure [ 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) ]
  Maximum change from baseline during each experimental session (mmHg)
• Change in heart rate [ 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) ]
  Maximum change from baseline during each experimental session (beats per minute)
• Change in peripheral oxygenation [ 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) ]
  Maximum change from baseline during each experimental session (SpO2)

Original Secondary Outcome Measures (submitted: November 30, 2016)

• Use of abortive/rescue medication [ Time Frame: Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary ]
  Number of times per week
• Attack-free time [ Time Frame: Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary ]
  Number of 24 hour days (may be nonconsecutive)
• Quality of life [ Time Frame: Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary ]
  Using the CDC's Health-Related Quality of Life (HRQOL) scale
• Psychedelic effects [ Time Frame: Taken daily on each experimental day after the resolution of psychedelic effects, approximately 6 hours after drug administration ]
  Using the 5-Dimensional Altered States of Consciousness (5D-ASC) scale
• Change in blood pressure [ 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) ]
  Maximum change from baseline during each experimental session (mmHg)
• Change in heart rate [ 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) ]
  Maximum change from baseline during each experimental session (beats per minute)
• Change in peripheral oxygenation [ 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) ]
  Maximum change from baseline during each experimental session (SpO2)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Psilocybin for the Treatment of Cluster Headache
• Official Title: Safety and Efficacy of Psilocybin for the Treatment of Headache Disorders
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Cluster Headache

Intervention

• Drug: 0.143 mg/kg Psilocybin or 10 mg Psilocybin
  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)
• Drug: 0.0143 mg/kg Psilocybin or 1 mg Psilocybin
  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)
• Drug: Placebo
  Microcrystalline cellulose capsule ingested on each of three test days (5 days apart +/- 1-2 days)

Study Arms

• Active Comparator: Psilocybin High Dose
  Intervention: Drug: 0.143 mg/kg Psilocybin or 10 mg Psilocybin
• Active Comparator: Psilocybin Low Dose
  Intervention: Drug: 0.0143 mg/kg Psilocybin or 1 mg Psilocybin
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 30, 2016): 24
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: November 2021
• Estimated Primary Completion Date: June 2021 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 21 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Emmanuelle Schindler, MD, PhD; 203-932-5711 ext 4335; emmanuelle.schindler@yale.edu

Contact: Christina Forte, BA; 203-932-5711 ext 2526; christina.forte@yale.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02981173
• Other Study ID Numbers: 1607018057
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Deepak C. D'Souza, Yale University
• Study Sponsor: Yale University

Collaborators

• Heffter Research Institute
• Cluster Headache-Trigeminal Autonomic Cephalalgia (CH-TAC), LLC

• Investigators: Not Provided
• PRS Account: Yale University
• Verification Date: January 2021