Clinical trial NCT06072898: A Randomized Neuroimaging Trial of Psilocybin in Depression
Official title: Engaging Mood Brain Circuits With Psilocybin: a Randomized Neuroimaging Trial in Depression
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Depressive Disorder
Major Depressive Disorder
Keywords: Psilocybin
Neuroimaging
MRI
Depression
Psychotherapy
Psychedelic
Lead sponsor: Sunnybrook Health Sciences Centre
Sponsor class: OTHER
First posted: 2023-10-10
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: This study will use a 2-group one-way delayed-start (AB/BB) design, with one group receiving placebo at the first visit and the investigational drug at second, and another group receiving the investigational drug at both visits. An interim analysis will be performed after 20 participants have completed the study to assess preliminary efficacy and safety trends.
Primary purpose: BASIC_SCIENCE

Brief summary: The goal of this neuroimaging clinical trial is to test whether psilocybin produces significant immediate changes in functional brain activity in networks associated with mood regulation and depression compared to placebo in patients with depression. The trial aims to determine if psilocybin:

1. Changes connectivity within brain networks associated with mood and depression
2. Changes blood flow in brain regions associated with mood and depression

Participants will be attend two treatment sessions where they receive an oral medication and supportive psychotherapy. At each session, participants will undergo an MRI scan after drug administration but prior to psychotherapy. Participants will be randomly to assigned to one of two groups that will receive, 1) microcrystalline cellulose (25mg) at the first visit and psilocybin (25mg) at the second visit, or 2) psilocybin (25mg) at both visits, respectively. Differences between groups will be compared to understand what effects on brain activity are specific to psilocybin.


Eligibility criteria: Inclusion Criteria:

* Able and voluntarily willing to provide written informed consent at the screening visit.
* Over 18 and under 65 years old
* Able to attend all study visits and complete all required assessment tools without assistance or alteration
* Have a responsible individual/caregiver who is able to monitor the participant at home for 24 hours after each treatment visit
* Must have a psychiatrist and/or general practitioner who is able to provide psychiatric follow-up care
* Mini International Neuropsychiatric Interview (MINI)-confirmed diagnosis of depressive disorder, recurrent or single episode, without psychotic features where the duration of the current episode is at least 3 months
* Depression of at least moderate severity as defined by a Hamilton Depression Rating Scale (HAMD-17) score \>17

Exclusion Criteria:

* Uncontrolled or insulin-dependent diabetes
* Women who are pregnant (self-report or via urine test), nursing, or planning a pregnancy during the timespan of the study
* History of seizure disorder except for seizures from electroconvulsive therapy and/or febrile seizures in childhood
* History of stroke, recent myocardial infarction (\< 1 year from signing of ICF), uncontrolled hypertension (blood pressure \> 140/90 mmHg) or clinically significant arrhythmia within 1 year of signing the ICF
* Abnormal and clinically significant results on a physical examination performed within one month of study participation by a general practitioner, vital signs, ECG, or laboratory test at screening
* QTc prolongation on ECG defined by \> 450 ms in males and \> 460 ms in females in V5 on a 12-lead ECG
* Positive urine drug screen for illicit drugs or drugs of abuse at screening, a week prior to treatment, and during the trial (any positive urine drug test will be reviewed with participants to determine the pattern of use and eligibility will be determined at the investigator's discretion)
* Serial blood counts to achieve a value to meet eligibility -- abnormalities in screening/baseline blood work (complete blood counts, electrolyte panel, etc.) will be reviewed by MD, then repeated serially until abnormalities resolve
* Any symptoms consistent with psychosis
* Any symptoms consistent with hypomania and/or mania as assessed by a psychiatrist
* Other personal circumstances or behavior judged to be incompatible with establishment of rapport or safe exposure to psilocybin
* Current or past history of bipolar I/II disorder, schizophrenia, schizoaffective disorder, psychotic disorder, or delusional disorder as assessed by a structured clinical interview (MINI)
* ≥ 1 suicide attempt in the past year requiring hospitalization, defined using the Columbia Suicide Severity Rating Scale (CSSRS) (Q6 (past year) = "y") and clinical interview with a psychiatrist
* History of substance use and/or alcohol use disorder, of moderate severity or greater, in the past 12 months
* Lifetime history of substance use disorder with a hallucinogen
* Lifetime history of substance-induced psychosis
* Depression secondary to other medical conditions or bipolar I and II disorder
* Family history of a first degree relative with a diagnosis of schizophrenia or a primary psychotic disorder and/or bipolar disorder
* Exposure to psilocybin or any other psychedelic in the past 12 months prior to screening and/or during the current MDE and use of psychedelics, such as ayahuasca/LSD, during the current depressive episode
* A clinical diagnosis of antisocial personality disorder and/or paranoid personality disorder (defined as meeting DSM-5.0 criteria) based on clinical interview and the MINI 7.0. Positive diagnoses on the MINI will be subject to confirmation at a clinical interview by a psychiatrist
* An active clinical diagnosis of borderline personality disorder as confirmed by the MINI 7.0
* Diagnosis of any mild or major neurocognitive disorder meeting DSM-5 criteria and based on clinical interview/cognitive screening by a psychiatrist
* Current enrolment in an interventional study for depression or participation in such within 30 days of screening
* Any other clinically significant cardiovascular, pulmonary, gastrointestinal, hepatic, renal or any other major concurrent illness that, in the opinion of the investigator, may interfere with the interpretation of the study results or constitute a health risk for the participant if he/she takes part in the study

Primary outcomes:
measure: Regional Blood Flow
timeFrame: Up to 3 weeks
measure: Change in Montgomery-Asberg Depression Rating Scale (MADRS)
timeFrame: Up to 6 weeks
Secondary outcomes:
measure: Functional Network Connectivity
timeFrame: Up to 3 weeks
measure: 17-item Hamilton Depression Rating Scale (GRID-HAMD-17)
timeFrame: 24 hours
measure: Incidence of response
timeFrame: up to 6 weeks
measure: Incidence of remission
timeFrame: up to 6 weeks
measure: Patient Health Questionnaire 9-item (PHQ-9)
timeFrame: up to 6 weeks
measure: 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR-16)
timeFrame: up to 6 weeks
measure: Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: up to 6 weeks
measure: Brief Psychiatric Rating Scale (BPRS)
timeFrame: up to 6 weeks
measure: Sheehan Disability Scale (SDS)
timeFrame: up to 6 weeks
measure: Generalized Anxiety Disorder-7 (GAD-7)
timeFrame: up to 6 weeks
measure: Snaith-Hamilton Pleasure Scale (SHAPS)
timeFrame: up to 6 weeks
measure: 6-Item Clinician Administered Dissociative Symptom Scale (CADSS-6)
timeFrame: up to 6 weeks
measure: Montreal Cognitive Assessment (MoCA)
timeFrame: up to 6 weeks
measure: Hopkins Verbal Learning Test-Revised (HVLT-R)
timeFrame: up to 6 weeks
measure: CANTAB Rapid Visual Information Processing
timeFrame: up to 6 weeks
measure: CANTAB Reaction Time
timeFrame: up to 6 weeks
measure: CANTAB Spatial Working Memory
timeFrame: up to 6 weeks
measure: CANTAB One Touch Stockings of Cambridge
timeFrame: up to 6 weeks
measure: CANTAB Delayed Matching to Sample
timeFrame: up to 6 weeks
measure: CANTAB Paired-Associates Learning
timeFrame: up to 6 weeks
measure: CANTAB Emotion Recognition Task
timeFrame: up to 6 weeks
measure: Revised Mystical Experience Questionnaire (MEQ30)
timeFrame: up to 8 weeks
measure: Persistent Effects Questionnaire (PEQ)
timeFrame: 24 hours
Other outcomes:
measure: Blood biomarkers
timeFrame: up to 5 weeks
Locations:
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
Study officials:
affiliation: Sunnybrook Health Sciences Centre
name: Sean M Nestor, PhD MD FRCPC
role: PRINCIPAL_INVESTIGATOR
affiliation: Sunnybrook Research Institute
name: Bradley J MacIntosh, PhD
role: PRINCIPAL_INVESTIGATOR
References: