Psilocybin for the Treatment of Cluster Headache

• ClinicalTrials.gov Identifier: NCT02981173
• Recruitment Status: Active, not recruiting
• First Posted: December 5, 2016
• Last Update Posted: July 28, 2022
• 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

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.

Condition or disease	Intervention/treatment	Phase
Cluster Headache	Drug: 0.143 mg/kg Psilocybin or 10 mg Psilocybin; Drug: 0.0143 mg/kg Psilocybin or 1 mg Psilocybin; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Safety and Efficacy of Psilocybin for the Treatment of Headache Disorders
• Study Start Date: November 2016
• Estimated Primary Completion Date: June 2023
• Estimated Study Completion Date: June 2023

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Psilocybin High Dose	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)
Active Comparator: Psilocybin Low Dose	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)
Placebo Comparator: Placebo	Drug: Placebo; Microcrystalline cellulose capsule ingested on each of three test days (5 days apart +/- 1-2 days)

Outcome Measures

Primary Outcome Measures :

1. 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
2. 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
3. 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)
4. 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)
5. 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)
6. 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)
7. 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
8. 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
9. 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

Secondary Outcome Measures :

1. 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
2. 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)
3. 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
4. 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
5. 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)
6. 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)
7. 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)

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Connecticut

VA Connecticut Healthcare System

West Haven, Connecticut, United States, 06516

Sponsors and Collaborators

Yale University

Heffter Research Institute

Cluster Headache-Trigeminal Autonomic Cephalalgia (CH-TAC), LLC

More Information

• Responsible Party: Deepak C. D'Souza, Professor of Psychiatry, Yale University
• ClinicalTrials.gov Identifier: NCT02981173
• Other Study ID Numbers: 1607018057
• First Posted: December 5, 2016
• Last Update Posted: July 28, 2022
• Last Verified: July 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Additional relevant MeSH terms:

Cluster Headache; Headache; Pain; Neurologic Manifestations; Trigeminal Autonomic Cephalalgias; Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Psilocybin; Hallucinogens; Physiological Effects of Drugs; Psychotropic Drugs