Clinical trial NCT03806985: Effects of Psilocybin in Concussion Headache
Official title: Safety and Efficacy of Psilocybin for the Treatment of Headache Disorders: Sub-Study II
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Post-Traumatic Headache
Keywords: psilocybin
Lead sponsor: Yale University
Sponsor class: OTHER
First posted: 2019-01-16
Enrollment: 12
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to investigate the effects of oral psilocybin in post-traumatic headache. Subjects will be randomized to receive placebo, low dose psilocybin, or high dose psilocybin on two separate test days approximately 14 days apart. Subjects will maintain a headache diary prior to, during, and after the treatments in order to document headache frequency and intensity, as well as associated symptoms. Blood samples will be drawn at various timepoints to measure levels of inflammatory peptides.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of post-traumatic headache
* Typical pattern of headache attacks with approximately two attacks or more weekly
* Attacks are managed by means involving no more than twice weekly triptan use

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, 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 5 half-lives of test days
* Use of serotonergic antiemetics (i.e. ondansetron) in the past 2 weeks
* Use of antidepressant medication (i.e. TCA, MAOI, SSRI) in the past 6 weeks
* Use of steroids or certain other immunomodulatory agents (i.e. azathioprine) in the past 2 weeks

Primary outcomes:
measure: Acute change in pain intensity
timeFrame: Measured at 0, 1, 2, 4, and 24 hours after drug administration
measure: Acute change in nausea/vomiting
timeFrame: Measured at 0, 1, 2, 4, and 24 hours after drug administration
measure: Acute change in photophobia
timeFrame: Measured at 0, 1, 2, 4, and 24 hours after drug administration
measure: Acute change in phonophobia
timeFrame: Measured at 0, 1, 2, 4, and 24 hours after drug administration
measure: Acute change in functional disability
timeFrame: Measured at 0, 1, 2, 4, and 24 hours after drug administration
measure: Time to first headache attack
timeFrame: Two weeks following each test session
measure: Time to last headache attack
timeFrame: Two weeks following each test session
measure: Change in headache attack frequency
timeFrame: From two weeks before first session to two weeks after second session using a headache diary
measure: Change in headache attack duration
timeFrame: From two weeks before first session to two weeks after second session using a headache diary
measure: Change in pain intensity of headache attacks
timeFrame: From two weeks before first session to two weeks after second session using a headache diary
measure: Change in intensity of nausea/vomiting during headache attacks
timeFrame: From two weeks before first session to two weeks after second session using a headache diary
measure: Change in intensity of photophobia during headache attacks
timeFrame: From two weeks before first session to two weeks after second session using a headache diary
measure: Change in intensity of phonophobia during headache attacks
timeFrame: From two weeks before first session to two weeks after second session using a headache diary
measure: Change in intensity of functional disability during headache attacks
timeFrame: From two weeks before first session to two weeks after second session using a headache diary
Secondary outcomes:
measure: Use of abortive/rescue medication
timeFrame: From two weeks before first session to two weeks after second session using a headache diary
measure: Headache attack-free time
timeFrame: From two weeks before first session to two weeks after second session using a headache diary
measure: Quality of life using the Centers for Disease Control (CDC) Health-Related Quality of Life Scale: Healthy Days Symptoms Module
timeFrame: From two weeks before first session to two weeks after second session using a headache diary
measure: Depression using Patient Health Questionnaire 9 (PHQ-9)
timeFrame: From two weeks before first session to two weeks after second session using a headache diary
measure: Suicide risk using the Columbia Suicide Severity Rating Scale (CSSRS)
timeFrame: From two weeks before first session to two weeks after second session using a headache diary
measure: Psychedelic effects using the 5-Dimensional Altered States of Consciousness (5D-ASC) scale
timeFrame: Taken on each test day approximately 6 hours after drug administration
measure: Change in blood pressure
timeFrame: Measured during each test session prior to drug administration, every 15 min in the first hour, every 30 min in the second hour, and then hourly for 4 hours or until resolution of psychedelic effects (~6 hours post drug)
measure: Change in heart rate
timeFrame: Measured during each test session prior to drug administration, every 15 min in the first hour, every 30 min in the second hour, and then hourly for 4 hours or until resolution of psychedelic effects (~6 hours post drug)
measure: Change in peripheral oxygenation
timeFrame: Measured during each test session prior to drug administration, every 15 min in the first hour, every 30 min in the second hour, and then hourly for 4 hours or until resolution of psychedelic effects (~6 hours post drug)
measure: Change in peripheral levels of calcitonin gene-related peptide (CGRP)
timeFrame: Measured during each test session prior to drug administration, and at 2 and 4 hours after drug administration
measure: Change in peripheral levels of pituitary adenylate cyclase-activating peptide (PACAP)
timeFrame: Measured during each test session prior to drug administration, and at 2 and 4 hours after drug administration
Other outcomes:
Locations:
city: West Haven
country: United States
facility: VA Connecticut Healthcare System
state: Connecticut
Study officials:
References: