Effects of Psilocybin in Concussion Headache

Post-Traumatic Headache Clinical Trial

Official title:

Safety and Efficacy of Psilocybin for the Treatment of Headache Disorders: Sub-Study II

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03806985
• Other study ID #: 1607018057.B
• Status: Terminated
• Phase: Phase 1
• Start date: March 28, 2019
• Est. completion date: June 27, 2023

Study information

• Verified date: October 2023
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 12
• Est. completion date: June 27, 2023
• Est. primary completion date: June 27, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Headache
• Post-Traumatic Headache

Intervention

Drug:
• Placebo oral capsule
microcrystalline cellulose capsule
• Low Dose Psilocybin
0.0143 mg/kg psilocybin capsule (weight-based option) or 1 mg psilocybin capsule (fixed-dose option)
• High Dose Psilocybin
0.143 mg/kg psilocybin capsule (weight-based option) or 10 mg psilocybin capsule (fixed-dose option)

Locations

Country	Name	City	State
United States	VA Connecticut Healthcare System	West Haven	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Yale University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Acute change in pain intensity	4-tiered pain score (0=none, 1=mild, 2=moderate, 3=severe)	Measured at 0, 1, 2, 4, and 24 hours after drug administration
Primary	Acute change in nausea/vomiting	4-tiered pain score (0=none, 1=mild, 2=moderate, 3=severe)	Measured at 0, 1, 2, 4, and 24 hours after drug administration
Primary	Acute change in photophobia	4-tiered pain score (0=none, 1=mild, 2=moderate, 3=severe)	Measured at 0, 1, 2, 4, and 24 hours after drug administration
Primary	Acute change in phonophobia	4-tiered pain score (0=none, 1=mild, 2=moderate, 3=severe)	Measured at 0, 1, 2, 4, and 24 hours after drug administration
Primary	Acute change in functional disability	4-tiered pain score (0=none, 1=mild, 2=moderate, 3=severe)	Measured at 0, 1, 2, 4, and 24 hours after drug administration
Primary	Time to first headache attack	Measured in days	Two weeks following each test session
Primary	Time to last headache attack	Measured in days	Two weeks following each test session
Primary	Change in headache attack frequency	Average number (number per week)	From two weeks before first session to two weeks after second session using a headache diary
Primary	Change in headache attack duration	Average duration (measured in hours)	From two weeks before first session to two weeks after second session using a headache diary
Primary	Change in pain intensity of headache attacks	Average pain intensity (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)	From two weeks before first session to two weeks after second session using a headache diary
Primary	Change in intensity of nausea/vomiting during headache attacks	Average intensity of nausea/vomiting (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)	From two weeks before first session to two weeks after second session using a headache diary
Primary	Change in intensity of photophobia during headache attacks	Average intensity of photophobia (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)	From two weeks before first session to two weeks after second session using a headache diary
Primary	Change in intensity of phonophobia during headache attacks	Average intensity of phonophobia (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)	From two weeks before first session to two weeks after second session using a headache diary
Primary	Change in intensity of functional disability during headache attacks	Average intensity of functional disability (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)	From two weeks before first session to two weeks after second session using a headache diary
Secondary	Use of abortive/rescue medication	number of times per week	From two weeks before first session to two weeks after second session using a headache diary
Secondary	Headache attack-free time	Number of 24 hour days (may be non-consecutive)	From two weeks before first session to two weeks after second session using a headache diary
Secondary	Quality of life using the Centers for Disease Control (CDC) Health-Related Quality of Life Scale: Healthy Days Symptoms Module	4 questions scored 0 to 30 each; higher numbers indicate worse quality of life.; (1) pain-related impairment, (2) mood symptoms, (3) anxiety symptoms, and (4) lack of sleep Percent change for each measure as well as total score (range 0 to 120) will be calculated.	From two weeks before first session to two weeks after second session using a headache diary
Secondary	Depression using Patient Health Questionnaire 9 (PHQ-9)	9 question self-report questionnaire to assess the presence of depression-related symptoms. Each question is rated on a scale of 0-3 (0 = Not at all; 1 = Several days; 2 = More than half the days; 3 = Nearly every day). Higher scores indicate greater presence of depression-related symptoms.; Total score is calculated. Total score 5-9 = minimal symptoms; total score 10-14 = Major Depression, mild; total score 15-19 = Major Depression, moderately severe; total score >20 = Major Depression severe.	From two weeks before first session to two weeks after second session using a headache diary
Secondary	Suicide risk using the Columbia Suicide Severity Rating Scale (CSSRS)	A 10-category assessment of suicidal ideation and behavior. 5 categories (scored "yes/no") relate to the presence of suicidal ideation. 5 categories (scored "yes/no") relate to the presence of suicidal behavior. A "yes" to any of the suicidal ideation categories indicates the presence of suicidal ideation; a "yes" to any of the suicidal behavior categories indicates the presence of suicidal behavior.	From two weeks before first session to two weeks after second session using a headache diary
Secondary	Psychedelic effects using the 5-Dimensional Altered States of Consciousness (5D-ASC) scale	94 questions scored 0 to 100 each; higher numbers indicate greater psychedelic effects Questions address 5 dimensions: (1) Oceanic boundlessness (score range 0-2700), (2) Dread of Ego Dissolution (score range 0-2100), (3) Visionary Restructuralization (score range 0-1800), (4) Auditory Alterations (score range 0-1600), and (5) Vigilance reduction (score range 0-1200) Score for each dimension as well as total score (range 0 to 9400) will be measured.	Taken on each test day approximately 6 hours after drug administration
Secondary	Change in blood pressure	Maximum change from baseline during each test day (mmHg)	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)
Secondary	Change in heart rate	Maximum change from baseline during each test day (beats per minute)	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)
Secondary	Change in peripheral oxygenation	Maximum change from baseline during each test day (SpO2)	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)
Secondary	Change in peripheral levels of calcitonin gene-related peptide (CGRP)	Change from baseline during each test day (pg/mg protein)	Measured during each test session prior to drug administration, and at 2 and 4 hours after drug administration
Secondary	Change in peripheral levels of pituitary adenylate cyclase-activating peptide (PACAP)	Change from baseline during each test day (pg/mg protein)	Measured during each test session prior to drug administration, and at 2 and 4 hours after drug administration