Clinical trial NCT06464367: Mechanistic Studies of Psilocybin in Headache Disorders
Official title: Mechanistic Studies of Psilocybin in Headache Disorders
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Migraine
Keywords: psilocybin
resting state functional connectivity
synaptic density
synaptic vessel glycoprotein 2A (SV2A)
circadian rhythm
sleep
inflammation
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: The Wallace Foundation
First posted: 2024-06-18
Enrollment: 50
Sex: ALL
Minimum age (years): 21
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: In previous clinical trial work, the investigators observed lasting reductions in headache burden after limited dosing of psilocybin. This purpose of this study is to examine potential sources for this observed effect. This study will measure brain resting state functional connectivity (fMRI), central synaptic density (SV2A PET), peripheral markers of inflammation, circadian rhythm (actigraphy), and sleep (sleep EEG) in both migraine and healthy control participants before and one week after the administration of psilocybin or an active control agent.


Eligibility criteria: Inclusion criteria:

* Age 21 to 70 (inclusive)
* Migraine disease per ICHD-3 criteria (for migraine participants) OR Healthy control patient

Exclusion criterion

* Unstable medical condition or serious nervous system pathology
* Pregnant, breastfeeding, lack of adequate birth control
* Psychotic or manic disorder
* Substance abuse in the prior 3 months
* Use of classic psychedelics (e.g., psilocybin, LSD, mescaline) in the past 6 months
* Use of cannabis or other THC products in the prior 2 weeks
* Urine toxicology positive to drugs of abuse
* The use of triptans (e.g., sumatriptan) or ditans (e.g., lasmiditan) more than twice weekly on average
* Use of serotonergic preventive therapies (i.e., taken chronically; amitriptyline, fluoxetine, imipramine, cyproheptadine) in the past 6 weeks
* Use of preventive or transitional treatments that produce spikes and waning of symptom relief (e.g., botulinum toxin, calcitonin gene-related peptide system targeting antibodies, peripheral nerve or ganglion blocks, chiropractic manipulation)
* History of a bleeding disorder or are currently taking anticoagulants (e.g., warfarin, enoxaparin, dabigatran, apixaban).
* Use of non-steroidal anti-inflammatory drugs (NSAIDs; e.g., ibuprofen, naproxen) in the 7 days before PET scan and 7 days after PET scan.

Primary outcomes:
measure: Baseline SV2A PET
timeFrame: from date of randomization until the date of first PET scan, assessed up to 6 months
measure: Baseline RSFC
timeFrame: from date of randomization until the date of first MRI, assessed up to 6 months
measure: Change in SV2A PET after drug administration
timeFrame: from date of first PET scan to the date of second PET scan, assessed up to 6 months
measure: Change in resting state functional connectivity (RSFC) after drug administration
timeFrame: from date of first MRI to the date of second MRI, assessed up to 6 months
Secondary outcomes:
measure: Change in TNF-alpha
timeFrame: from screening to 7 days after drug administration
measure: Change in IL-1beta
timeFrame: from screening to 7 days after drug administration
measure: Change in IL-6
timeFrame: from screening to 7 days after drug administration
measure: Change in calcitonin gene-related peptide (CGRP)
timeFrame: from screening to 7 days after drug administration
measure: Change in pituitary adenylate cyclase activating polypeptide (PACAP)
timeFrame: from screening to 7 days after drug administration
measure: Change in bedtime (via actigraphy)
timeFrame: from screening through 14 days after drug administration
measure: Change in get-up time (via actigraphy)
timeFrame: from screening through 14 days after drug administration
measure: Change in daily active period (via actigraphy)
timeFrame: from screening through 14 days after drug administration
measure: Change in daily rest period (via actigraphy)
timeFrame: from screening through 14 days after drug administration
measure: Change in REM latency (via sleep electroencephalography)
timeFrame: from screening to 7 days after drug administration
measure: Change in percent REM (via sleep electroencephalography)
timeFrame: from screening to 7 days after drug administration
measure: Change in sleep efficiency (via sleep electroencephalography)
timeFrame: from screening to 7 days after drug administration
measure: Adverse events
timeFrame: from screening through 3 months after drug administration
Other outcomes:
measure: Acute change in TNF-alpha during drug administration
timeFrame: 0, 120, and 240 minutes after drug administration
measure: Acute change in IL-1beta during drug administration
timeFrame: 0, 120, and 240 minutes after drug administration
measure: Acute change in IL-6 during drug administration
timeFrame: 0, 120, and 240 minutes after drug administration
measure: Acute change in calcitonin gene related peptide (CGRP) during drug administration
timeFrame: 0, 120, and 240 minutes after drug administration
measure: Acute change in pituitary adenylate cyclase activating polypeptide (PACAP) during drug administration
timeFrame: 0, 120, and 240 minutes after drug administration
measure: Acute change in mean arterial pressure (MAP) during drug administration
timeFrame: 0, 30, 60, 120, 180, 240, 300, and 360 minutes after drug administration
measure: Acute change in heart rate during drug administration
timeFrame: 0, 30, 60, 120, 180, 240, 300, and 360 minutes after drug administration
measure: Acute change in SpO2 during drug administration
timeFrame: 0, 30, 60, 120, 180, 240, 300, and 360 minutes after drug administration
measure: Acute change in general drug effects during drug administration
timeFrame: 0, 30, 60, 120, 180, 240, 300, and 360 minutes after drug administration
measure: Acute psychedelic effects during drug administration
timeFrame: up to 8 hours after drug administration
Locations:
city: West Haven
country: United States
facility: VA Connecticut Healthcare System
state: Connecticut
Study officials:
References: