Treatment of Persisting Symptoms After Concussion With Psilocybin Assisted Therapy (PatACT)

University of Calgary

Status and phase: Enrolling; Phase 1

Conditions: Persisting Symptoms After Concussion

Treatments: Drug: Psilocybin

Study type: Interventional

Funder types: Other

Identifiers

NCT06615908

REB24-0334

Details and patient eligibility

About

The goal of this randomized controlled trial is to evaluate the safety, feasibility, and efficacy of psilocybin assisted therapy as an intervention to reduce symptom burden in adult patients (aged 18-65) with persisting symptoms after concussion (PSaC).

This trail will test the following 2 aims:

AIM 1 : To test the safety and feasibility of an active psilocybin-assisted psychotherapy to an active control for patients with PSaC.

AIM 2: To evaluate the efficacy of an active psilocybin-assisted psychotherapy compared to an active control as a treatment for PSaC.

Participants will be asked to:

• Complete a 2-part screening process
• Attend a baseline assessment
• Complete a psychoeducation preparation session(s)
• Attend psilocybin administration session (receive high dose [25mg] or low dose psilocybin [1mg])
• Complete 5 weekly sessions of Acceptance and commitment therapy (ACT)
• Repeat outcome measures at 1-week, 4 weeks, 3 months, and 6 months post-psilocybin administration (online only at 6 months).

Full description

The overall objective of this study is to evaluate the safety, feasibility, and efficacy of psilocybin assisted therapy administered with Acceptance and Commitment Therapy (ACT) as an intervention to reduce symptom burden in patients with persisting symptoms after concussion (PSaC).

This trail will test the following 2 aims:

AIM 1 : To test the safety and feasibility of an active/high dose (25mg) psilocybin-assisted psychotherapy to an active control (1mg) for adults with PSaC. Safety will be determined through the reporting of adverse events and response following psilocybin for each participant up to 6-months. Feasibility will be determined through recruitment, enrollment, and adherence rates.

AIM 2: To evaluate the efficacy of an active/high dose (25mg) psilocybin-assisted psychotherapy compared to an active control (1mg) as a treatment for PPCS at 1-week, 4 weeks, 3 months, and 6 months post-psilocybin administration. The primary efficacy outcome will be the change in PSaC burden (RPQ).

The secondary efficacy outcomes will include measures of headache, dizziness, mood, anxiety, post-traumatic stress, cognitive flexibility, emotional regulation, and quality of life.

A total of 40 male and female patients between the ages of 18-65 with a diagnosis of mild traumatic brain injury (American College of Rehabilitation Medicine 2023 criteria) who meet criteria for persisting symptoms after concussion (ICD-10) within 3 months to 5 years will be recruited from Calgary brain injury clinics and the community.

All patients will undergo a thorough, 2-part screening procedure. Eligible participants will be randomly allocated 1:1 to either the high dose (20 participants) or low dose (20 participants) psilocybin groups. All participants will be asked to attend a baseline session consisting of clinical and behavioural outcome measures, followed by a pre-dosing psychoeducation session. Following the single dosing session, participants will complete 5 weekly ACT sessions. Outcome measure assessments will be repeated at 1-week, 4 weeks, 3 months, and 6 months post-dosing.

Enrollment: 40 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

• Individuals of all sexes, gender identities, and ethnicities
• Ages 18 to 65 years at the time of screening
• Diagnosis of concussion based on the 2024 ACRM criteria
• Meet ICD-10 criteria for PSaC for at least 3-months to a maximum of 5 years
• Have an overall RPQ score ≥ 13 with 3 or more symptoms scored ≥3
• Limited lifetime use of serotonergic hallucinogens
• Ability to read/write English

An individual who meets any of the following criteria will be excluded from participation in this study:

• Severe or moderate substance use disorder other than nicotine in past 6 months
• Lifetime diagnosis of schizophrenia or bipolar disorders (or first or second-degree relative)
• Active suicidal ideation or serious attempt within the past 1 year.
• Current pregnancy or nursing, trying to become pregnant
• Any notable abnormality on ECG or routine medical blood laboratory test
• Insulin-dependent diabetes; if taking oral hypoglycemic agent, then no history of hypoglycemia
• Epilepsy with a history of seizures
• Current or recent (within 12 weeks) participation in a clinical trial
• Cognitive impairment (SLUMS score <20)
• Suffered a moderate/severe TBI at least once in lifetime
• Any other circumstances that, in the opinion of the investigators, compromises participant safety

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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40 participants in 2 patient groups

High dose (25mg)

Experimental group

Description:

High Dose (25mg) PEX010 (Oral Psilocybin), 25mg; single dose (20 participants) administered 24hrs prior to first ACT session

Treatment:

Drug: Psilocybin

Low dose (1mg)

Active Comparator group

Description:

Low Dose (1mg) PEX010 (Oral Psilocybin), 1mg; single dose (20 participants)administered 24hrs prior to first ACT session

Treatment:

Drug: Psilocybin