Effects of Psilocybin in Post-Traumatic Headache

• Sponsor: Yale University
• Information provided by (Responsible Party): Yale University

Tracking Information

• First Submitted Date: January 14, 2019
• First Posted Date: January 16, 2019
• Last Update Posted Date: June 12, 2019
• Actual Study Start Date: March 28, 2019
• Estimated Primary Completion Date: January 15, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 14, 2019)

• Acute change in pain intensity [ Time Frame: Measured at 0, 1, 2, 4, and 24 hours after drug administration ]
  4-tiered pain score (0=none, 1=mild, 2=moderate, 3=severe)
• Acute change in nausea/vomiting [ Time Frame: Measured at 0, 1, 2, 4, and 24 hours after drug administration ]
  4-tiered pain score (0=none, 1=mild, 2=moderate, 3=severe)
• Acute change in photophobia [ Time Frame: Measured at 0, 1, 2, 4, and 24 hours after drug administration ]
  4-tiered pain score (0=none, 1=mild, 2=moderate, 3=severe)
• Acute change in phonophobia [ Time Frame: Measured at 0, 1, 2, 4, and 24 hours after drug administration ]
  4-tiered pain score (0=none, 1=mild, 2=moderate, 3=severe)
• Acute change in functional disability [ Time Frame: Measured at 0, 1, 2, 4, and 24 hours after drug administration ]
  4-tiered pain score (0=none, 1=mild, 2=moderate, 3=severe)
• Time to first headache attack [ Time Frame: Two weeks following each test session ]
  Measured in days
• Time to last headache attack [ Time Frame: Two weeks following each test session ]
  Measured in days
• Change in headache attack frequency [ Time Frame: From two weeks before first session to two weeks after second session using a headache diary ]
  Average number (number per week)
• Change in headache attack duration [ Time Frame: From two weeks before first session to two weeks after second session using a headache diary ]
  Average duration (measured in hours)
• Change in pain intensity of headache attacks [ Time Frame: From two weeks before first session to two weeks after second session using a headache diary ]
  Average pain intensity (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
• Change in intensity of nausea/vomiting during headache attacks [ Time Frame: From two weeks before first session to two weeks after second session using a headache diary ]
  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 [ Time Frame: From two weeks before first session to two weeks after second session using a headache diary ]
  Average intensity of photophobia (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
• Change in intensity of phonophobia during headache attacks [ Time Frame: From two weeks before first session to two weeks after second session using a headache diary ]
  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 [ Time Frame: From two weeks before first session to two weeks after second session using a headache diary ]
  Average intensity of functional disability (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)

• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT03806985 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: January 14, 2019)

• Use of abortive/rescue medication [ Time Frame: From two weeks before first session to two weeks after second session using a headache diary ]
  number of times per week
• Headache attack-free time [ Time Frame: From two weeks before first session to two weeks after second session using a headache diary ]
  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 [ Time Frame: From two weeks before first session to two weeks after second session using a headache diary ]
  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) [ Time Frame: From two weeks before first session to two weeks after second session using a headache diary ]
  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) [ Time Frame: From two weeks before first session to two weeks after second session using a headache diary ]
  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 [ Time Frame: Taken on each test day approximately 6 hours after drug administration ]
  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 [ 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) ]
  Maximum change from baseline during each test day (mmHg)
• Change in heart rate [ 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) ]
  Maximum change from baseline during each test day (beats per minute)
• Change in peripheral oxygenation [ 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) ]
  Maximum change from baseline during each test day (SpO2)
• Change in peripheral levels of calcitonin gene-related peptide (CGRP) [ Time Frame: Measured during each test session prior to drug administration, and at 2 and 4 hours after drug administration ]
  Change from baseline during each test day (pg/mg protein)
• Change in peripheral levels of pituitary adenylate cyclase-activating peptide (PACAP) [ Time Frame: Measured during each test session prior to drug administration, and at 2 and 4 hours after drug administration ]
  Change from baseline during each test day (pg/mg protein)

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Effects of Psilocybin in Post-Traumatic Headache
• Official Title: Safety and Efficacy of Psilocybin for the Treatment of Headache Disorders: Sub-Study II
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Double (Participant, Care Provider); Primary Purpose: Treatment
• Condition: Post-Traumatic Headache

Intervention

• Drug: Placebo oral capsule
  microcrystalline cellulose capsule
• Drug: Low Dose Psilocybin
  0.0143 mg/kg psilocybin capsule
• Drug: High Dose Psilocybin
  0.143 mg/kg psilocybin capsule

Study Arms

• Experimental: Placebo/Low Dose Psilocybin
  Subjects in this arm receive placebo in the first session and low dose psilocybin in the second session.
  Interventions:

  • Drug: Placebo oral capsule
  • Drug: Low Dose Psilocybin
• Experimental: Placebo/High Dose Psilocybin
  Subjects in this arm receive placebo in the first session and high dose psilocybin in the second session.
  Interventions:

  • Drug: Placebo oral capsule
  • Drug: High Dose Psilocybin
• Experimental: Low Dose Psilocybin/Placebo
  Subjects in this arm receive low dose psilocybin in the first session and placebo in the second session.
  Interventions:

  • Drug: Placebo oral capsule
  • Drug: Low Dose Psilocybin
• Experimental: High Dose Psilocybin/Placebo
  Subjects in this arm receive high dose psilocybin in the first session and placebo in the second session.
  Interventions:

  • Drug: Placebo oral capsule
  • Drug: High Dose Psilocybin
• Experimental: High Dose Psilocybin/Low Dose Psilocybin
  Subjects in this arm receive high dose psilocybin in the first session and low dose psilocybin in the second session.
  Interventions:

  • Drug: Low Dose Psilocybin
  • Drug: High Dose Psilocybin
• Experimental: Low Dose Psilocybin/High Dose Psilocybin
  Subjects in this arm receive low dose psilocybin in the first session and high dose psilocybin in the second session.
  Interventions:

  • Drug: Low Dose Psilocybin
  • Drug: High Dose Psilocybin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 14, 2019): 24
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 15, 2022
• Estimated Primary Completion Date: January 15, 2021 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 21 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Emmanuelle Schindler, MD, PhD; 203-932-5711 ext 4335; emmanuelle.schindler@yale.edu

Contact: Leigh T Flynn, BS; 203-932-5711 ext 2557; leigh.flynn@yale.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03806985
• Other Study ID Numbers: 1607018057.B
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Yale University
• Study Sponsor: Yale University
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Yale University
• Verification Date: June 2019