Clinical trial NCT04218539: Repeat Dosing of Psilocybin in Migraine Headache
Official title: Repeat Dosing of Psilocybin in Headache Disorders
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Migraine Headache
Keywords: psilocybin
inflammation
calcitonin gene-related peptide (CGRP)
pituitary adenylate cyclase-activating peptide (PACAP)
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: The Wallace Foundation
First posted: 2020-01-06
Enrollment: 18
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In seeking to understand the capacity for psilocybin to reduce migraine headache burden, this study will investigate single and repeated dosing of psilocybin up to two doses. In seeking to identify an underlying mechanism in psilocybin's effects, neuroinflammatory markers for migraine headache will be measured.

Detailed description: Migraine headache is a common medical condition and a top cause of disability worldwide. Treatment options for migraine headache are many and varied, though an approximated 10% of migraineurs is refractory to medication and thus, there is a need to develop alternative treatments. There is anecdotal evidence supporting lasting therapeutic effects after limited dosing of psilocybin and related compounds in headache disorders. The cause of this unique effect remains unknown, though the drug class has demonstrable anti-inflammatory activity, a biological process relevant to migraine and other headache disorders. In seeking to understand the capacity for psilocybin to reduce migraine headache burden, this study will investigate single and repeated dosing of psilocybin up to two doses. In seeking to identify an underlying mechanism in psilocybin's effects, neuroinflammatory markers for migraine headache will be measured. The results from this study will serve in the development of larger investigations seeking to understand the effects of psilocybin and related compounds in headache disorders.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of migraine headache per ICHD-3 criteria
* Typical pattern of migraine attacks with approximately two migraines or more weekly
* Attacks are managed by means involving no more than twice weekly triptan use

Exclusion Criteria:

* Axis I psychotic or manic disorder (e.g., schizophrenia, bipolar I, depression with psychosis)
* Axis I psychotic or manic 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 abuse within the past 3 months (excluding tobacco)
* Urine toxicology positive to drugs of abuse
* Alcohol use of \>21 drinks per week (males); \>14 drinks per week (females; NIAAA guidelines)
* Use of alcohol in the week prior to the first test day
* 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
* Use of migraine onabotulinum toxin (i.e., Botox) or monoclonal antibodies against CGRP or its receptor (i.e., erenumab) in the past month or while therapeutic effects are still present

Primary outcomes:
measure: Change in migraine attack frequency
timeFrame: From two weeks before the first session to two months after second session using a headache diary
measure: Change in pain intensity of migraine attacks
timeFrame: From two weeks before the first session to two months after second session using a headache diary
measure: Change in duration of migraine attacks
timeFrame: From two weeks before the first session to two months after second session using a headache diary
measure: Change in intensity of photophobia (light sensitivity)
timeFrame: From two weeks before the first session to two months after second session using a headache diary
measure: Change in intensity of phonophobia (noise sensitivity)
timeFrame: From two weeks before the first session to two months after second session using a headache diary
measure: Average intensity of nausea/vomiting
timeFrame: From two weeks before the first session to two months after second session using a headache diary
measure: Change in functional disability
timeFrame: From two weeks before the first session to two months after second session using a headache diary
Secondary outcomes:
measure: Use of abortive/rescue medication
timeFrame: From two weeks before the first session to two months after second session using a headache diary
measure: Time to first migraine attack
timeFrame: From the second session until two months after second session using a headache diary
measure: Migraine attack-free time
timeFrame: From two weeks before the first session to two months 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 the first session to two months after second session using a headache diary
measure: Psychedelic effects using the 5-Dimensional Altered States of Consciousness (5D-ASC) scale
timeFrame: Starting on the first test day until the second test day approximately one week later; taken both test days approximately 6 hours after drug administration
measure: Change in blood pressure- Systolic
timeFrame: Starting on the first test day until the second test day approximately one week later; measured both test sessions before drug administration, every 30 min in the first hour, then hourly for 4 hours or until resolution of drug effects (~6hrs after drug)
measure: Change in blood pressure- Diastolic
timeFrame: Starting on the first test day until the second test day approximately one week later; measured both test sessions before drug administration, every 30 min in the first hour, then hourly for 4 hours or until resolution of drug effects (~6hrs after drug)
measure: Change in heart rate
timeFrame: Starting on the first test day until the second test day approximately one week later; measured both test sessions before drug administration, every 30 min in the first hour, then hourly for 4 hours or until resolution of drug effects (~6hrs after drug)
measure: Change in peripheral oxygenation
timeFrame: Starting on the first test day until the second test day approximately one week later; measured both test sessions before drug administration, every 30 min in the first hour, then hourly for 4 hours or until resolution of drug effects (~6hrs after drug)
measure: Change in peripheral calcitonin gene-related peptide (CGRP) levels
timeFrame: Approximately 3 months; measured at screening, on both test days (0, 2, and 4 hours after drug administration), and follow-up (~2 months after second test day)
measure: Change in pituitary adenylate cyclase-activating peptide (PACAP) levels
timeFrame: Approximately 3 months; measured at screening, on both test days (0, 2, and 4 hours after drug administration), and follow-up (~2 months after second test day)
Other outcomes:
Locations:
city: West Haven
country: United States
facility: VA Connecticut Healthcare System
state: Connecticut
Study officials:
References: