Investigating the Therapeutic Effects of Psilocybin in Treatment-Resistant Post-Traumatic Stress Disorder

• ClinicalTrials.gov Identifier: NCT05243329
• Recruitment Status: Not yet recruiting
• First Posted: February 17, 2022
• Last Update Posted: March 15, 2022
• Sponsor: Halucenex Life Sciences Inc.
• Collaborators: Everest Clinical Research; True North Therapeutics
• Information provided by (Responsible Party): Halucenex Life Sciences Inc.

Tracking Information

• First Submitted Date: December 15, 2021
• First Posted Date: February 17, 2022
• Last Update Posted Date: March 15, 2022
• Estimated Study Start Date: April 2022
• Estimated Primary Completion Date: May 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 14, 2022)

• Primary efficacy of psilocybin using the 11-Dimension Altered States of Consciousness (11D-ASC) will assess [ Time Frame: Day 14 ]
  This is a 42 item questionnaire assessing patient-rated subjective intensity of psilocybin's effects
• PTSD symptom severity as measured by the Clinician-Administered PTSD Scale (CAPS-5) [ Time Frame: Screening to 6 months follow up ]
  Total CAPS-5 Scores range from 0-80. Higher scores indicate greater symptom severity.
• Subjective distress caused by traumatic events as measured by the Impact of Events Scale Revised (IES-R). [ Time Frame: Screening to 6 months follow up ]
  The IES-R is a 22-item self-report measure where respondents are asked to identify a specific stressful life event and then indicate how much they were distressed or bothered during the past seven days by each "difficulty" listed. Items are rated on a 5-point scale ranging from 0 ("not at all") to 4 ("extremely"). The IES-R yields a total score (ranging from 0 to 88).
• Symptoms of Psychopathology as measured by the Symptom Checklist 90-R (SC90-R). [ Time Frame: Screening to 6 months follow up ]
  The 90 items in the SC90-R are assessed by the subject using a 5-point rating scale.
• Symptom severity, treatment response, and the efficacy of treatment studies of patients with mental disorders as measured by the Clinical Global Impression - Improvement (CGI-I)/ Clinical Global Impression - Severity (CGI-S). [ Time Frame: Day 22 ]
  The CGI-S scale is a 7-point, clinician-rated scale (ranging from 1 to 7, with 1 indicating a "normal state" and 7 indicating "among the most extremely ill patients").

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 14, 2022)

• Anxiety as measured by the Beck Anxiety Inventory (BAI). [ Time Frame: Up to 6 month follow up ]
  The BAI is a 21-item self-report inventor. Total BAI Scores range from 0-63; higher scores indicate more severe anxiety.
• Anxiety as measured by the State Trait Anxiety Inventory - Trait Version (STAI-T). [ Time Frame: Up to 6 month follow up ]
  The STAI-T scale consists of 20 items on a 4-point scale; Higher scores indicate greater anxiety.
• Depression as measured by the Beck Depression Inventory (BDI). [ Time Frame: Up to 6 month follow up ]
  The BDI is a 21-item, self-report rating inventory with each item scored on a scale value of 0 to 3; higher total scores indicating more severe depression symptoms.
• Depression as measured by the Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR). [ Time Frame: Up to 6 month follow up ]
  The QIDS-SR contains 16 items, with each item scored from 0 to 3.
• Impairments in daily living as measured by the Sheehan Disability Scale (SDS). [ Time Frame: Up to 6 month follow up ]
  This is a 3-item, clinician administered questionnaire with all items rated on an 11-point continuum, with higher scores indicating more severe impairment. (0 meaning "no impairment" to 10 meaning "most severe").
• Addiction severity as measured by the Addiction Severity Index (ASI). [ Time Frame: Up to 6 month follow up ]
• Body Mass Index (BMI) [ Time Frame: Up to 6 month follow up ]

• 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: Investigating the Therapeutic Effects of Psilocybin in Treatment-Resistant Post-Traumatic Stress Disorder
• Official Title: Investigating the Therapeutic Effects of Psilocybin in Treatment-Resistant Post-Traumatic

Brief Summary

Post-traumatic stress disorder (PTSD) is a complex disorder expressed as a variety of neurobiological symptoms, including anxiety, re-experiencing, hyperarousal, and avoidance symptoms, along with comorbidities such as anxiety, depression, and increased risk for self-medicating substance abuse. Currently, there are only two approved medications in the United States (US) for PTSD, paroxetine and sertraline.

Psychedelic medications, including psilocybin, have recently received breakthrough designation by the US Food and Drug Administration (FDA) for other psychiatric indications. Although no formal clinical trials have yet investigated psychedelic substances for the treatment of PTSD, the available evidence warrants such an investigation. The present study aims to investigate the effect of psilocybin on treatment-resistant PTSD.

Detailed Description

Post-traumatic stress disorder (PTSD) is a complex disorder expressed as a variety of neurobiological symptoms, including anxiety, re-experiencing, hyperarousal, and avoidance symptoms, along with comorbidities such as anxiety, depression, and increased risk for self-medicating substance abuse. Currently, there are only two approved medications in the United States (US) for PTSD, paroxetine and sertraline. These selective serotonin reuptake inhibitors (SSRIs) have limited efficacy. Furthermore, there is a lack of efficacious pharmacotherapy for treatment-resistant PTSD; PTSD remains a chronic and sometimes debilitating condition. New research into other treatment options for PTSD are warranted.

Psychedelic medications, including psilocybin, have recently received breakthrough designation by the US Food and Drug Administration (FDA) for other psychiatric indications. Psilocybin has received breakthrough designation for treatment of depression. Research on psilocybin has shown that it facilitates fear extinction in mice and promotes neuroplasticity, increasing neurogenesis, spinogenesis and synaptogenesis. These properties may contribute to antidepressive and anxiolytic effects. Psilocybin also reduces activity in the amygdala during threat responses; decreased amygdala reactivity is correlated with positive mood. This is particularly relevant since individuals with PTSD showed increased reactivity in the amygdala, which may increase the ability to process traumatic memories. Although no formal clinical trials have yet investigated psychedelic substances for the treatment of PTSD, the available evidence warrants such an investigation. The present study aims to investigate the effect of psilocybin on treatment-resistant PTSD.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Health Services Research

Condition

• Treatment Resistant Disorders
• Post Traumatic Stress Disorder

Intervention

Drug: Psilocybin

10 mg or 25 mg oral aqueous psilocybin solution

Study Arms

Experimental: Psilocybin treatment for treatment-resistant PTSD

Experimental Treatment:

Experimental: Psilocybin

10mg (low dose) on Day 7

25mg (high dose) on Day 14

Treatment Description:

Drug: Psilocybin drug product suspension

Psilocybin is manufactured as a bulk API powder. The psilocybin drug product suspension is prepared by a compounding pharmacist at the clinic site. The psilocybin drug product suspension will be mixed in a glass with water to produce the psilocybin solution for oral consumption. Subjects will be instructed to orally consume the study medication in the glass in its entirety.

Psilocybin will be administered in the following doses and at the following time points for this study:

• 1 mL of 10mg/mL (low dose) on Day 7 (10 mg)
• 2.5 mL of 10 mg/mL (high dose) on Day 14 (25 mg)

Intervention: Drug: Psilocybin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: February 14, 2022): 20
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: November 2022
• Estimated Primary Completion Date: May 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

- After signing and dating the informed consent documents, subject eligibility will be assessed. Subjects must meet the following criteria to be eligible for enrollment into the study.

1. Subjects must be ≥18 and ≤70 years of age.
2. Subjects must meet the Diagnostic & Statistical Manual of Mental Disorders - Version V (DSM-V) criteria for the diagnosis of crime or war-related chronic PTSD.
3. Subjects must have treatment-resistant PTSD symptoms, defined as a CAPS score of ≥50 (signifying moderate to severe symptoms) following at least 3 months of prior SSRI or serotonin-norepinephrine reuptake inhibitor (SNRI) treatment in addition to at least 4 months of psychotherapy (adapted from Mithoefer et al, 2011).
4. Subjects must be able to communicate in English.

Exclusion Criteria:

• Subjects meeting any of the following criteria will not be eligible for participation in the study:

  1. Pregnant women and those not using effective contraception (e.g., oral contraceptive pill, injection, implant, patch, vaginal ring, intrauterine coil, intrauterine device, tubal ligation, or barrier method).
  2. Uncontrolled hypertension or BP ≥140/90 mmHg over 2 days, with at least 4 BP assessments completed.
  3. In the clinical judgement of the investigator, any hazard-posing medical, emotional, or significant character disorder or condition rendering unsuitability for the study. For example, poorly controlled diabetes, severe cardiovascular disease, seizure disorders, sleep apnea disorders (suspected or ineffectively treated), untrustworthiness, suicidality, etc.
  4. Any use of methamphetamines or any injection drug abuse in the past 30 days and/or a positive test for drugs of abuse (e.g., cocaine, amphetamines, opiates, benzodiazepines, etc.).
  5. Any other significant substance use disorder that may interfere with study objectives including consuming >5 cups of caffeinated coffee a day or inability, without discomfort, to refrain from smoking cigarettes or cannabis, or consuming alcohol for 7 hours.
  6. Blood draw or needle phobia.
  7. Borderline, schizoid, or schizotypal personality disorder.
  8. Suicidal attempt or active ideation in past 30 days.
  9. BMI <14 or >42.
  10. Axis I disorders, except anxiety disorders, depression, or controlled eating disorders. Any other Axis I disorder including an uncontrolled eating disorder (e.g., purging or anorexia or worsening of directionally undesirable weight change of 5 kg in past 30 days).
  11. Healthy participants with a first degree relative with a significant Axis 1 psychotic, dissociative, or mood disorder, except depression.
  12. Use of any investigational drug, hallucinogen, or ketamine/esketamine within the past 30 days, or plan to use during the study.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: William J Fleming, BA; 902-448-0716; bill.fleming@halucenex.com

Contact: David D James, PhD; 902-233-6053; david.james@halucenex.com

• Listed Location Countries: Canada

Administrative Information

• NCT Number: NCT05243329
• Other Study ID Numbers: HLS-001-2022
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Halucenex Life Sciences Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Halucenex Life Sciences Inc.
• Original Study Sponsor: Same as current

Collaborators

• Everest Clinical Research
• True North Therapeutics

• Investigators: Not Provided
• PRS Account: Halucenex Life Sciences Inc.
• Verification Date: March 2022