Back to resultsEffects of Psilocybin in Concussion Headache
Primary Purpose
Post-Traumatic Headache
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Placebo oral capsule
Low Dose Psilocybin
High Dose Psilocybin
Sponsored by
About this trial
This is an interventional treatment trial for Post-Traumatic Headache focused on measuring psilocybin
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
Sites / Locations
- VA Connecticut Healthcare System
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Placebo/Low Dose Psilocybin
Placebo/High Dose Psilocybin
Low Dose Psilocybin/Placebo
High Dose Psilocybin/Placebo
High Dose Psilocybin/Low Dose Psilocybin
Low Dose Psilocybin/High Dose Psilocybin
Arm Description
Subjects in this arm receive placebo in the first session and low dose psilocybin in the second session.
Subjects in this arm receive placebo in the first session and high dose psilocybin in the second session.
Subjects in this arm receive low dose psilocybin in the first session and placebo in the second session.
Subjects in this arm receive high dose psilocybin in the first session and placebo in the second session.
Subjects in this arm receive high dose psilocybin in the first session and low dose psilocybin in the second session.
Subjects in this arm receive low dose psilocybin in the first session and high dose psilocybin in the second session.
Outcomes
Primary Outcome Measures
Acute change in pain intensity
4-tiered pain score (0=none, 1=mild, 2=moderate, 3=severe)
Acute change in nausea/vomiting
4-tiered pain score (0=none, 1=mild, 2=moderate, 3=severe)
Acute change in photophobia
4-tiered pain score (0=none, 1=mild, 2=moderate, 3=severe)
Acute change in phonophobia
4-tiered pain score (0=none, 1=mild, 2=moderate, 3=severe)
Acute change in functional disability
4-tiered pain score (0=none, 1=mild, 2=moderate, 3=severe)
Time to first headache attack
Measured in days
Time to last headache attack
Measured in days
Change in headache attack frequency
Average number (number per week)
Change in headache attack duration
Average duration (measured in hours)
Change in pain intensity of headache attacks
Average pain intensity (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
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)
Change in intensity of photophobia during headache attacks
Average intensity of photophobia (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
Change in intensity of phonophobia during headache attacks
Average intensity of phonophobia (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
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)
Secondary Outcome Measures
Use of abortive/rescue medication
number of times per week
Headache attack-free time
Number of 24 hour days (may be non-consecutive)
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.
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.
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.
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.
Change in blood pressure
Maximum change from baseline during each test day (mmHg)
Change in heart rate
Maximum change from baseline during each test day (beats per minute)
Change in peripheral oxygenation
Maximum change from baseline during each test day (SpO2)
Change in peripheral levels of calcitonin gene-related peptide (CGRP)
Change from baseline during each test day (pg/mg protein)
Change in peripheral levels of pituitary adenylate cyclase-activating peptide (PACAP)
Change from baseline during each test day (pg/mg protein)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03806985
Brief Title
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
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Terminated
Why Stopped
Challenging to recruit qualifying subjects
Study Start Date
March 28, 2019 (Actual)
Primary Completion Date
June 27, 2023 (Actual)
Study Completion Date
June 27, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yale University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Post-Traumatic Headache
Keywords
psilocybin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare Provider
Allocation
Randomized
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo/Low Dose Psilocybin
Arm Type
Experimental
Arm Description
Subjects in this arm receive placebo in the first session and low dose psilocybin in the second session.
Arm Title
Placebo/High Dose Psilocybin
Arm Type
Experimental
Arm Description
Subjects in this arm receive placebo in the first session and high dose psilocybin in the second session.
Arm Title
Low Dose Psilocybin/Placebo
Arm Type
Experimental
Arm Description
Subjects in this arm receive low dose psilocybin in the first session and placebo in the second session.
Arm Title
High Dose Psilocybin/Placebo
Arm Type
Experimental
Arm Description
Subjects in this arm receive high dose psilocybin in the first session and placebo in the second session.
Arm Title
High Dose Psilocybin/Low Dose Psilocybin
Arm Type
Experimental
Arm Description
Subjects in this arm receive high dose psilocybin in the first session and low dose psilocybin in the second session.
Arm Title
Low Dose Psilocybin/High Dose Psilocybin
Arm Type
Experimental
Arm Description
Subjects in this arm receive low dose psilocybin in the first session and high dose psilocybin in the second session.
Intervention Type
Drug
Intervention Name(s)
Placebo oral capsule
Intervention Description
microcrystalline cellulose capsule
Intervention Type
Drug
Intervention Name(s)
Low Dose Psilocybin
Intervention Description
0.0143 mg/kg psilocybin capsule (weight-based option) or 1 mg psilocybin capsule (fixed-dose option)
Intervention Type
Drug
Intervention Name(s)
High Dose Psilocybin
Intervention Description
0.143 mg/kg psilocybin capsule (weight-based option) or 10 mg psilocybin capsule (fixed-dose option)
Primary Outcome Measure Information:
Title
Acute change in pain intensity
Description
4-tiered pain score (0=none, 1=mild, 2=moderate, 3=severe)
Time Frame
Measured at 0, 1, 2, 4, and 24 hours after drug administration
Title
Acute change in nausea/vomiting
Description
4-tiered pain score (0=none, 1=mild, 2=moderate, 3=severe)
Time Frame
Measured at 0, 1, 2, 4, and 24 hours after drug administration
Title
Acute change in photophobia
Description
4-tiered pain score (0=none, 1=mild, 2=moderate, 3=severe)
Time Frame
Measured at 0, 1, 2, 4, and 24 hours after drug administration
Title
Acute change in phonophobia
Description
4-tiered pain score (0=none, 1=mild, 2=moderate, 3=severe)
Time Frame
Measured at 0, 1, 2, 4, and 24 hours after drug administration
Title
Acute change in functional disability
Description
4-tiered pain score (0=none, 1=mild, 2=moderate, 3=severe)
Time Frame
Measured at 0, 1, 2, 4, and 24 hours after drug administration
Title
Time to first headache attack
Description
Measured in days
Time Frame
Two weeks following each test session
Title
Time to last headache attack
Description
Measured in days
Time Frame
Two weeks following each test session
Title
Change in headache attack frequency
Description
Average number (number per week)
Time Frame
From two weeks before first session to two weeks after second session using a headache diary
Title
Change in headache attack duration
Description
Average duration (measured in hours)
Time Frame
From two weeks before first session to two weeks after second session using a headache diary
Title
Change in pain intensity of headache attacks
Description
Average pain intensity (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
Time Frame
From two weeks before first session to two weeks after second session using a headache diary
Title
Change in intensity of nausea/vomiting during headache attacks
Description
Average intensity of nausea/vomiting (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
Time Frame
From two weeks before first session to two weeks after second session using a headache diary
Title
Change in intensity of photophobia during headache attacks
Description
Average intensity of photophobia (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
Time Frame
From two weeks before first session to two weeks after second session using a headache diary
Title
Change in intensity of phonophobia during headache attacks
Description
Average intensity of phonophobia (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
Time Frame
From two weeks before first session to two weeks after second session using a headache diary
Title
Change in intensity of functional disability during headache attacks
Description
Average intensity of functional disability (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
Time Frame
From two weeks before first session to two weeks after second session using a headache diary
Secondary Outcome Measure Information:
Title
Use of abortive/rescue medication
Description
number of times per week
Time Frame
From two weeks before first session to two weeks after second session using a headache diary
Title
Headache attack-free time
Description
Number of 24 hour days (may be non-consecutive)
Time Frame
From two weeks before first session to two weeks after second session using a headache diary
Title
Quality of life using the Centers for Disease Control (CDC) Health-Related Quality of Life Scale: Healthy Days Symptoms Module
Description
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.
Time Frame
From two weeks before first session to two weeks after second session using a headache diary
Title
Depression using Patient Health Questionnaire 9 (PHQ-9)
Description
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.
Time Frame
From two weeks before first session to two weeks after second session using a headache diary
Title
Suicide risk using the Columbia Suicide Severity Rating Scale (CSSRS)
Description
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.
Time Frame
From two weeks before first session to two weeks after second session using a headache diary
Title
Psychedelic effects using the 5-Dimensional Altered States of Consciousness (5D-ASC) scale
Description
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.
Time Frame
Taken on each test day approximately 6 hours after drug administration
Title
Change in blood pressure
Description
Maximum change from baseline during each test day (mmHg)
Time Frame
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)
Title
Change in heart rate
Description
Maximum change from baseline during each test day (beats per minute)
Time Frame
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)
Title
Change in peripheral oxygenation
Description
Maximum change from baseline during each test day (SpO2)
Time Frame
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)
Title
Change in peripheral levels of calcitonin gene-related peptide (CGRP)
Description
Change from baseline during each test day (pg/mg protein)
Time Frame
Measured during each test session prior to drug administration, and at 2 and 4 hours after drug administration
Title
Change in peripheral levels of pituitary adenylate cyclase-activating peptide (PACAP)
Description
Change from baseline during each test day (pg/mg protein)
Time Frame
Measured during each test session prior to drug administration, and at 2 and 4 hours after drug administration
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
VA Connecticut Healthcare System
City
West Haven
State/Province
Connecticut
ZIP/Postal Code
06516
Country
United States
12. IPD Sharing Statement
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Effects of Psilocybin in Concussion Headache
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