NCT03806985

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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
12

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Mar 2019

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 14, 2019

Completed
2 days until next milestone

First Posted

Study publicly available on registry

January 16, 2019

Completed
2 months until next milestone

Study Start

First participant enrolled

March 28, 2019

Completed
4.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 27, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 27, 2023

Completed
Last Updated

October 12, 2023

Status Verified

October 1, 2023

Enrollment Period

4.3 years

First QC Date

January 14, 2019

Last Update Submit

October 11, 2023

Conditions

Keywords

psilocybin

Outcome Measures

Primary Outcomes (14)

  • 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

  • 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

  • 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

  • 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

  • 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

  • Time to first headache attack

    Measured in days

    Two weeks following each test session

  • Time to last headache attack

    Measured in days

    Two weeks following each test session

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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 Outcomes (11)

  • Use of abortive/rescue medication

    From two weeks before first session to two weeks after second session using a headache diary

  • Headache attack-free time

    From two weeks before first session to two weeks after second session using a headache diary

  • Quality of life using the Centers for Disease Control (CDC) Health-Related Quality of Life Scale: Healthy Days Symptoms Module

    From two weeks before first session to two weeks after second session using a headache diary

  • Depression using Patient Health Questionnaire 9 (PHQ-9)

    From two weeks before first session to two weeks after second session using a headache diary

  • Suicide risk using the Columbia Suicide Severity Rating Scale (CSSRS)

    From two weeks before first session to two weeks after second session using a headache diary

  • +6 more secondary outcomes

Study Arms (6)

Placebo/Low Dose Psilocybin

EXPERIMENTAL

Subjects in this arm receive placebo in the first session and low dose psilocybin in the second session.

Drug: Placebo oral capsuleDrug: Low Dose Psilocybin

Placebo/High Dose Psilocybin

EXPERIMENTAL

Subjects in this arm receive placebo in the first session and high dose psilocybin in the second session.

Drug: Placebo oral capsuleDrug: High Dose Psilocybin

Low Dose Psilocybin/Placebo

EXPERIMENTAL

Subjects in this arm receive low dose psilocybin in the first session and placebo in the second session.

Drug: Placebo oral capsuleDrug: Low Dose Psilocybin

High Dose Psilocybin/Placebo

EXPERIMENTAL

Subjects in this arm receive high dose psilocybin in the first session and placebo in the second session.

Drug: Placebo oral capsuleDrug: High Dose Psilocybin

High Dose Psilocybin/Low Dose Psilocybin

EXPERIMENTAL

Subjects in this arm receive high dose psilocybin in the first session and low dose psilocybin in the second session.

Drug: Low Dose PsilocybinDrug: High Dose Psilocybin

Low Dose Psilocybin/High Dose Psilocybin

EXPERIMENTAL

Subjects in this arm receive low dose psilocybin in the first session and high dose psilocybin in the second session.

Drug: Low Dose PsilocybinDrug: High Dose Psilocybin

Interventions

microcrystalline cellulose capsule

High Dose Psilocybin/PlaceboLow Dose Psilocybin/PlaceboPlacebo/High Dose PsilocybinPlacebo/Low Dose Psilocybin

0.0143 mg/kg psilocybin capsule (weight-based option) or 1 mg psilocybin capsule (fixed-dose option)

High Dose Psilocybin/Low Dose PsilocybinLow Dose Psilocybin/High Dose PsilocybinLow Dose Psilocybin/PlaceboPlacebo/Low Dose Psilocybin

0.143 mg/kg psilocybin capsule (weight-based option) or 10 mg psilocybin capsule (fixed-dose option)

High Dose Psilocybin/Low Dose PsilocybinHigh Dose Psilocybin/PlaceboLow Dose Psilocybin/High Dose PsilocybinPlacebo/High Dose Psilocybin

Eligibility Criteria

Age21 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

VA Connecticut Healthcare System

West Haven, Connecticut, 06516, United States

Location

MeSH Terms

Conditions

Post-Traumatic Headache

Interventions

Psilocybin

Condition Hierarchy (Ancestors)

Headache Disorders, SecondaryHeadache DisordersBrain DiseasesCentral Nervous System DiseasesNervous System Diseases

Intervention Hierarchy (Ancestors)

Indole AlkaloidsAlkaloidsHeterocyclic CompoundsIndolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingTryptaminesIndolizidinesIndolizines

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, CARE PROVIDER
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 14, 2019

First Posted

January 16, 2019

Study Start

March 28, 2019

Primary Completion

June 27, 2023

Study Completion

June 27, 2023

Last Updated

October 12, 2023

Record last verified: 2023-10

Locations