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Psilocybin for the Treatment of Migraine Headache

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03341689
Recruitment Status : Active, not recruiting
First Posted : November 14, 2017
Last Update Posted : February 25, 2022
Sponsor:
Information provided by (Responsible Party):
Deepak C. D'Souza, Yale University

Tracking Information
First Submitted Date  ICMJE November 9, 2017
First Posted Date  ICMJE November 14, 2017
Last Update Posted Date February 25, 2022
Actual Study Start Date  ICMJE November 1, 2017
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 18, 2020)
  • Change in migraine headache days [ Time Frame: From two weeks before first session to two weeks after second session using a headache diary ]
    Average days (number of days per week)
  • Change in migraine 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 migraine 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 migraine 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 migraine attacks [ Time Frame: From two weeks before first session to two weeks after second session using a headache diary ]
    Average intensity (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
  • Change in intensity of photophobia [ Time Frame: From two weeks before first session to two weeks after second session using a headache diary ]
    Average intensity (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
  • Change in intensity of phonophobia [ Time Frame: From two weeks before first session to two weeks after second session using a headache diary ]
    Average intensity (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
  • Change in migraine attack-related functional disability [ Time Frame: From two weeks before first session to two weeks after second session using a headache diary ]
    Average disability (4-tiered pain score; 0=none, 1=mild, 2=moderate, 3=severe)
Original Primary Outcome Measures  ICMJE
 (submitted: November 9, 2017)
  • Acute change in pain intensity [ Time Frame: Measured at 0, 1, 2, 4, and 24 hours after drug administration ]
    4-tiered pain score (1=none, 2=mild, 3=moderate, 4=severe)
  • Acute change in nausea/vomiting [ Time Frame: Measured at 0, 1, 2, 4, and 24 hours after drug administration ]
    4-tiered pain score (1=none, 2=mild, 3=moderate, 4=severe)
  • Acute change in photophobia [ Time Frame: Measured at 0, 1, 2, 4, and 24 hours after drug administration ]
    4-tiered pain score (1=none, 2=mild, 3=moderate, 4=severe)
  • Acute change in phonophobia [ Time Frame: Measured at 0, 1, 2, 4, and 24 hours after drug administration ]
    4-tiered pain score (1=none, 2=mild, 3=moderate, 4=severe)
  • Acute change in functional disability [ Time Frame: Measured at 0, 1, 2, 4, and 24 hours after drug administration ]
    4-tiered pain score (1=none, 2=mild, 3=moderate, 4=severe)
  • Time to first migraine attack [ Time Frame: Two weeks following each test session ]
    Measured in days
  • Time to last migraine attack [ Time Frame: Two weeks following each test session ]
    Measured in days
  • Change in migraine 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 migraine 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 migraine 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; 1=none, 2=mild, 3=moderate, 4=severe)
  • Change in intensity of nausea/vomiting during migraine attacks [ Time Frame: From two weeks before first session to two weeks after second session using a headache diary ]
    Average intensity (4-tiered pain score; 1=none, 2=mild, 3=moderate, 4=severe)
  • Change in intensity of photophobia [ Time Frame: From two weeks before first session to two weeks after second session using a headache diary ]
    Average intensity (4-tiered pain score; 1=none, 2=mild, 3=moderate, 4=severe)
  • Change in intensity of phonophobia [ Time Frame: From two weeks before first session to two weeks after second session using a headache diary ]
    Average intensity (4-tiered pain score; 1=none, 2=mild, 3=moderate, 4=severe)
  • Change in functional disability [ Time Frame: From two weeks before first session to two weeks after second session using a headache diary ]
    Average disability (4-tiered pain score; 1=none, 2=mild, 3=moderate, 4=severe)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 18, 2020)
  • Change in the 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 days (number of days per week using a migraine abortive)
  • Time to first migraine attack [ Time Frame: From the day of each session until two weeks after each test session ]
    Measured in days
  • Time to second migraine attack [ Time Frame: From the day of each session until two weeks after each test session ]
    Measured in days
  • 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 three months 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.
  • 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 minutes in the first hour, every 30 minutes in the second hour, and then hourly for 4 hours or until resolution of psychedelic effects (~6 hours post drug) ]
    Maximum change in mean arterial blood pressure 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)
Original Secondary Outcome Measures  ICMJE
 (submitted: November 9, 2017)
  • 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
  • Migraine 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 [ Time Frame: From two weeks before first session to three months after second session using a headache diary ]
    Using the CDC's Health-Related Quality of Life Scale
  • Psychedelic effects [ Time Frame: Taken on each test day approximately 6 hours after drug administration ]
    Using the 5-Dimensional Altered States of Consciousness (5D-ASC) scale
  • 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)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Psilocybin for the Treatment of Migraine Headache
Official Title  ICMJE Safety and Efficacy of Psilocybin for the Treatment of Headache Disorders: Sub-Study I
Brief Summary The purpose of this study is to investigate the effects of oral psilocybin in migraine headache. Subjects will each receive a dose of placebo and a dose of psilocybin approximately 14 days apart. Subjects will be randomized to the order of treatment and they will be randomized to receive either low or high dose psilocybin. 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. This preliminary study will inform on the basic effects of psilocybin in migraine headache and inform on the design of larger, more definitive studies.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
Condition  ICMJE Migraine Headache
Intervention  ICMJE
  • Drug: High Dose Psilocybin
    0.143 mg/kg psilocybin capsule
  • Drug: Low Dose Psilocybin
    0.0143 mg/kg psilocybin capsule
  • Drug: Placebo
    microcrystalline cellulose capsule
Study Arms  ICMJE
  • 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: Low Dose Psilocybin
    • Drug: Placebo
  • 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: High Dose Psilocybin
    • Drug: Placebo
  • 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: Low Dose Psilocybin
    • Drug: Placebo
  • 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: High Dose Psilocybin
    • Drug: Placebo
Publications * Schindler EAD, Sewell RA, Gottschalk CH, Luddy C, Flynn LT, Lindsey H, Pittman BP, Cozzi NV, D'Souza DC. Exploratory Controlled Study of the Migraine-Suppressing Effects of Psilocybin. Neurotherapeutics. 2021 Jan;18(1):534-543. doi: 10.1007/s13311-020-00962-y. Epub 2020 Nov 12.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: November 9, 2017)
24
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosis of migraine headache per ICHD-3beta 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
  • Age 21 to 65

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03341689
Other Study ID Numbers  ICMJE 1607018057.A
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  ICMJE Not Provided
Current Responsible Party Deepak C. D'Souza, Yale University
Original Responsible Party Yale University
Current Study Sponsor  ICMJE Yale University
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Yale University
Verification Date February 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP