Cluster Headache
Conditions
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.
Interventions
DRUG0.143 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)
DRUG0.0143 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)
DRUGPlacebo
Microcrystalline cellulose capsule ingested on each of three test days (5 days apart +/- 1-2 days)
Sponsors
Heffter Research Institute
Ceruvia Lifesciences
CH TAC LLC
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in the change in the duration of attacks between 1st and 2nd round | 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 |
| Time to last attack after completion of pulse regimen | 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 | 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 | 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 | 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) | 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 | 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 | 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 |
| Time to first attack after completion of pulse regimen | Two months following the completion of pulse regimen (after completion of experimental sessions 1, 2, and 3) | Measured in days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Attack-free time | 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 | 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 | 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 | 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 | 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 | 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) |
| Use of abortive/rescue medication | Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary | Number of times per week |
Countries
United States
Outcome results
None listed