Clinical trial NCT06615908: Treatment of Persistent Post-concussive Symptoms With Psilocybin Assisted Therapy
Official title: A Randomized Double Blinded Controlled Trial for the Treatment of Persistent Post-concussion Symptoms With Psilocybin Assisted Therapy: A Safety and Feasibility Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Persistent Post-concussive Symptoms
Keywords: Psychotherapy
Psilocybin
Concussion
Mild Traumatic Brain Injury
Acceptance and Commitment Therapy
Lead sponsor: University of Calgary
Sponsor class: OTHER
Collaborators: name: University of British Columbia
First posted: 2024-09-27
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blinded randomized control trial
Primary purpose: TREATMENT

Brief summary: 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 persistent post-concussion symptoms (PPCS).

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 PPCS

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

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 5-6 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).

Detailed 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 persistent post-concussion symptoms (PPCS).

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 PPCS. 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 PPCS 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 persistent post-concussion symptoms (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 5-6 weekly ACT sessions. Outcome measure assessments will be repeated at 1-week, 4 weeks, 3 months, and 6 months post-dosing.

Eligibility 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 PPCS 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
* Not actively in litigation related to their mTBI or other injury

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: Throughout study completion, an average of 6 months
measure: Study protocol efficacy
timeFrame: Throughout study completion, an average of 6 months
measure: Study protocol feasibility
timeFrame: Screening, enrolment, intervention, and participation up to study end point (6-months)
Secondary outcomes:
measure: Montgomery-Asberg Depression Rating Scale Self report (MADRS-S)
timeFrame: Throughout study completion, an average of 6 months [assessed at baseline, and 1-week, 4 weeks, 3 months, and 6 months post-dosing]
measure: Generalized Anxiety Disorder-7 (GAD-7).
timeFrame: Throughout study completion, an average of 6 months [assessed at baseline, and 1-week, 4 weeks, 3 months, and 6 months post-dosing]
measure: Sleep and Concussion Questionnaire (SCQ)
timeFrame: Throughout study completion, an average of 6 months [assessed at baseline, and 1-week, 4 weeks, 3 months, and 6 months post-dosing]
measure: Headache Impact Test (HIT-6).
timeFrame: Throughout study completion, an average of 6 months [assessed at baseline, and 1-week, 4 weeks, 3 months, and 6 months post-dosing]
measure: Dizziness Handicap Questionnaire (DHI)
timeFrame: Throughout study completion, an average of 6 months [assessed at baseline, and 1-week, 4 weeks, 3 months, and 6 months post-dosing]
measure: PTSD Checklist for DSM-5 (PCL-5)
timeFrame: Throughout study completion, an average of 6 months [assessed at baseline, and 1-week, 4 weeks, 3 months, and 6 months post-dosing]
measure: The Quality of Life after Brain Injury (QOLIBRI)
timeFrame: Throughout study completion, an average of 6 months [assessed at baseline, and 1-week, 4 weeks, 3 months, and 6 months post-dosing]
measure: Difficulties in Emotion Regulation Scale (DERS)
timeFrame: Throughout study completion, an average of 6 months [assessed at baseline, and 1-week, 4 weeks, 3 months, and 6 months post-dosing]
measure: Think Aloud Task
timeFrame: Throughout study completion, an average of 6 months [assessed at baseline, and 1-week, 4 weeks, and 3 months post-dosing]
measure: Probabilistic Reversal Learning Task
timeFrame: Throughout study completion, an average of 6 months [assessed at baseline, and 1-week, 4 weeks, and 3 months post-dosing]
measure: The Acceptance and Action Questionnaire II (AAQ-II)
timeFrame: Throughout study completion, an average of 6 months [assessed at baseline, and 1-week, 4 weeks, 3 months, and 6 months post-dosing]
measure: The Acceptance and Action after Brain Injury Questionnaire (AAQ-ABI)
timeFrame: Throughout study completion, an average of 6 months [assessed at baseline, and 1-week, 4 weeks, 3 months, and 6 months post-dosing]
measure: Cognitive Fusion Questionnaire (CFQ-7)
timeFrame: Throughout study completion, an average of 6 months [assessed at baseline, and 1-week, 4 weeks, 3 months, and 6 months post-dosing]
measure: Bergs Card Sorting Task
timeFrame: Throughout study completion, an average of 6 months [assessed at baseline, and 1-week, 4 weeks, and 3 months post-dosing]
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
Study officials:
affiliation: University of Calgary
name: Chantel T Debert, MD MSc FRCPC
role: PRINCIPAL_INVESTIGATOR
References: