Clinical trial NCT05243329: 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 Stress Disorder
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Treatment Resistant Disorders
Post Traumatic Stress Disorder
Lead sponsor: Halucenex Life Sciences Inc.
Sponsor class: INDUSTRY
Collaborators: name: KGK Science Inc.
First posted: 2022-02-17
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: HEALTH_SERVICES_RESEARCH

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.

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 TR-PTSD.
3. Subjects must have treatment-resistant PTSD symptoms, defined as a CAPS score of ≥30 (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 individuals and those of childbearing age 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. Suicidal attempt or active ideation deemed to present risk of suicide as judged by study clinical staff in past 30 days..
  8. BMI \<14 or \>42 or the Qualified investigator deems the patient sufficiently healthy to participate.
  9. Current or previously diagnosed schizophrenia spectrum or other psychotic disorders, including schizophrenia, schizoaffective disorder, schizotypal disorder, schizophreniform disorder or brief psychotic disorder; current or previous history of bipolar disorder, or obsessive-compulsive disorder.
  10. Any uncontrolled eating disorder (e.g., purging or anorexia or worsening of directionally undesirable weight change of 5 kg in past 30 days).
  11. Subjects with a diagnosis of DSM-5 personality disorder which has a major impact on the subject's current psychiatric status
  12. Use of any investigational drug, hallucinogen, or ketamine/esketamine within the past 30 days, or plan to use during the study.

Primary outcomes:
measure: Primary efficacy of psilocybin using the 11-Dimension Altered States of Consciousness (11D-ASC) will assess
timeFrame: Day 14
measure: PTSD symptom severity as measured by the Clinician-Administered PTSD Scale (CAPS-5)
timeFrame: Screening to 12 months follow up
measure: PTSD symptom severity as measured by the Posttraumatic Checklist for the DSM-5 (PCL-5)
timeFrame: Screening to 12 months follow up
measure: Subjective distress caused by traumatic events as measured by the Impact of Events Scale Revised (IES-R).
timeFrame: Screening to 12 months follow up
measure: Symptoms of Psychopathology as measured by the Symptom Checklist 90-R (SC90-R).
timeFrame: Screening to 12 months follow up
measure: 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).
timeFrame: Day 22
Secondary outcomes:
measure: Anxiety as measured by the Beck Anxiety Inventory (BAI).
timeFrame: Up to 12 month follow up
measure: Anxiety as measured by the State Trait Anxiety Inventory - Trait Version (STAI-T).
timeFrame: Up to 6 month follow up
measure: Depression as measured by the Beck Depression Inventory (BDI).
timeFrame: Up to 12 month follow up
measure: Depression as measured by the Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR).
timeFrame: Up to 12 month follow up
measure: Impairments in daily living as measured by the Sheehan Disability Scale (SDS).
timeFrame: Up to 12 month follow up
measure: Body Mass Index (BMI)
timeFrame: Up to 12 month follow up
measure: Trauma Related Nightmare Survey
timeFrame: Up to 12 month follow up
Other outcomes:
Locations:
city: Windsor
country: Canada
facility: Halucenex Life Sciences Inc.
state: Nova Scotia
Study officials:
affiliation: Halucenex Life Sciences
name: Lisa Batten, PhD
role: STUDY_DIRECTOR
affiliation: Contracted
name: Paige Stevens, MD
role: PRINCIPAL_INVESTIGATOR
References: