Psilocybin for the Treatment of Cluster Headache

NCT02981173 | Completed Phase 1

• 1 other identifier: 1607018057
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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.

Conditions

Cluster Headache

Outcome Measures

Primary Outcomes (9)

• Time to first attack after completion of pulse regimen

  Measured in days

  Two months following the completion of pulse regimen (after completion of experimental sessions 1, 2, and 3)

• Time to last attack after completion of pulse regimen

  Measured in days

  Six months following the completion of pulse regimen (after completion of experimental sessions 1, 2, and 3)

• Change in frequency of attacks

  Average number of attacks (number per week)

  Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary

• Change in intensity of attacks

  Average intensity of attacks (1-10 on visual analog scale)

  Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary

• Change in duration of attacks

  Average duration of attacks (minutes)

  Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary

• Change in cluster period duration compared to typical cluster period (episodic subjects only)

  Duration of cluster period after intervention (days)

  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

• 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

  Measured from 2 weeks before to 2 months after completion for each of the two pulse regimens using a headache diary

• 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

  Measured from 2 weeks before to 2 months after completion for each of the two pulse regimens using a headache diary

• 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

  Measured from 2 weeks before to 2 months after completion for each of the two pulse regimens using a headache diary

Secondary Outcomes (7)

• Use of abortive/rescue medication

  Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary

• Attack-free time

  Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary

• Health-Related Quality of life

  Measured from 2 weeks before to 2 months after completion of pulse regimen using a headache diary

• Psychedelic effects

  Taken daily on each experimental day after the resolution of psychedelic effects, approximately 6 hours after drug administration

• 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)

Study Arms (3)

Psilocybin High Dose

ACTIVE COMPARATOR

Drug: 0.143 mg/kg Psilocybin or 10 mg Psilocybin

Psilocybin Low Dose

ACTIVE COMPARATOR

Drug: 0.0143 mg/kg Psilocybin or 1 mg Psilocybin

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

0.143 mg/kg Psilocybin or 10 mg Psilocybin DRUG

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)

Psilocybin High Dose

0.0143 mg/kg Psilocybin or 1 mg Psilocybin DRUG

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)

Psilocybin Low Dose

Placebo DRUG

Microcrystalline cellulose capsule ingested on each of three test days (5 days apart +/- 1-2 days)

Placebo

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Yale University: lead
• Heffter Research Institute: collaborator
• Ceruvia Lifesciences: collaborator
• CH TAC LLC: collaborator

Study Sites (1)

VA Connecticut Healthcare System

West Haven, Connecticut, 06516, United States

Location

Related Publications (1)

• Schindler EAD, Sewell RA, Gottschalk CH, Flynn LT, Zhu Y, Pittman BP, Cozzi NV, D'Souza DC. Psilocybin pulse regimen reduces cluster headache attack frequency in the blinded extension phase of a randomized controlled trial. J Neurol Sci. 2024 May 15;460:122993. doi: 10.1016/j.jns.2024.122993. Epub 2024 Apr 2.

  PMID: 38581739 DERIVED

MeSH Terms

Conditions

Cluster Headache

Interventions

Psilocybin

Condition Hierarchy (Ancestors)

Trigeminal Autonomic Cephalalgias; Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychiatry

Study Record Dates

• First Submitted: November 11, 2016
• First Posted: December 5, 2016
• Study Start: December 5, 2016
• Primary Completion: June 30, 2022
• Study Completion: October 21, 2022
• Last Updated: December 15, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)