Psilocybin for the Treatment of Migraine Headache

Study Description

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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, in both the short and long-term.

Condition or disease	Intervention/treatment	Phase
Migraine Headache	Drug: High Dose Psilocybin; Drug: Low Dose Psilocybin; Drug: Placebo	Phase 1

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	24 participants
Allocation:	Randomized
Intervention Model:	Crossover Assignment
Masking:	Double (Participant, Care Provider)
Primary Purpose:	Treatment
Official Title:	Safety and Efficacy of Psilocybin for the Treatment of Headache Disorders: Sub-Study I
Actual Study Start Date :	November 1, 2017
Estimated Primary Completion Date :	November 1, 2019
Estimated Study Completion Date :	March 1, 2020

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Placebo/Low Dose Psilocybin; Subjects in this arm receive placebo in the first session and low dose psilocybin in the second session.	Drug: Low Dose Psilocybin; 0.0143 mg/kg psilocybin capsule; Drug: Placebo; microcrystalline cellulose capsule
Experimental: Placebo/High Dose Psilocybin; Subjects in this arm receive placebo in the first session and high dose psilocybin in the second session.	Drug: High Dose Psilocybin; 0.143 mg/kg psilocybin capsule; Drug: Placebo; microcrystalline cellulose capsule
Experimental: Low Dose Psilocybin/Placebo; Subjects in this arm receive low dose psilocybin in the first session and placebo in the second session.	Drug: Low Dose Psilocybin; 0.0143 mg/kg psilocybin capsule; Drug: Placebo; microcrystalline cellulose capsule
Experimental: High Dose Psilocybin/Placebo; Subjects in this arm receive high dose psilocybin in the first session and placebo in the second session.	Drug: High Dose Psilocybin; 0.143 mg/kg psilocybin capsule; Drug: Placebo; microcrystalline cellulose capsule

Outcome Measures

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Primary Outcome Measures :

1. 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)
2. 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)
3. 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)
4. 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)
5. 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)
6. Time to first migraine attack [ Time Frame: Two weeks following each test session ]
   Measured in days
7. Time to last migraine attack [ Time Frame: Two weeks following each test session ]
   Measured in days
8. 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)
9. 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)
10. 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)
11. 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)
12. 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)
13. 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)
14. 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)

Secondary Outcome Measures :

1. 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
2. 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)
3. 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.

4. 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.
5. 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)
6. 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)
7. 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)

Eligibility Criteria

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Ages Eligible for Study:	21 Years to 65 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

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Contacts

Contact: Emmanuelle Schindler, MD, PhD	203-932-5711 ext 4335	emmanuelle.schindler@va.gov
Contact: Christina Luddy, BS	203-932-5711 ext 4549	christina.luddy@yale.edu

Locations

United States, Connecticut
VA Connecticut Healthcare System, West Haven Campus	Recruiting
West Haven, Connecticut, United States, 06516
Contact: Emmanuelle Schindler, MD, PhD 203-932-5711 ext 4335 emmanuelle.schindler@va.gov
Contact: Christina Luddy, BS 203-932-5711 ext 4549 christina.luddy@yale.edu
Principal Investigator: Deepak C D'Souza, M.D.

Sponsors and Collaborators

Yale University

More Information

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Responsible Party:	Deepak C. D'Souza, Professor, Yale University
ClinicalTrials.gov Identifier:	NCT03341689 History of Changes
Other Study ID Numbers:	1607018057.A
First Posted:	November 14, 2017
Last Update Posted:	February 4, 2019
Last Verified:	January 2019

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

Keywords provided by Deepak C. D'Souza, Yale University:

Psilocybin

Additional relevant MeSH terms:

Psilocybin; Migraine Disorders; Headache; Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases	Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Hallucinogens; Physiological Effects of Drugs; Psychotropic Drugs