NCT06072898 - A Randomized Neuroimaging Trial of Psilocybin in Depression | Crick

Eligibility

Sex: ALLMin age: 18 YearsMax age: 64 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Able and voluntarily willing to provide written informed consent at the screening visit * Over 18 and under 65 years old * Able to complete all protocol required assessment tools without any assistance or alteration to the copyrighted assessments, and to comply with all study visits * Must have a responsible individual/caregiver who is able to monitor the participant at home for 24 hours after each treatment visit in the study * Must have a psychiatrist and/or general practitioner who is able to provide psychiatric follow-up care * Have a Mini-International Neuropsychiatric Interview (MINI) confirmed diagnosis of MDD, 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: * 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) * A clinical diagnosis of antisocial personality disorder and/or paranoid personality disorder (defined as meeting DSM-5 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. * 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 * Any symptoms consistent with psychosis * Any symptoms consistent with hypomania and/or mania as assessed by a psychiatrist * Personal history of ≥ 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 * Other personal circumstances or behavior judged to be incompatible with establishment of rapport or safe exposure to psilocybin * Women who are pregnant (self-report or via urine test), nursing, or planning a pregnancy * Lifetime history of substance use disorder with a hallucinogen * Lifetime history of substance-induced psychosis * 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) * 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 * Uncontrolled or insulin-dependent diabetes * History of seizure disorder except for seizures from electroconvulsive therapy and/or febrile seizures in childhood * Diagnosis of any mild or major neurocognitive disorder meeting DSM-5 criteria and based on clinical interview/cognitive screening by a psychiatrist * 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 * 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 * 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 * History of substance use and/or alcohol use disorder, of moderate severity or greater, in the past 12 months * Current enrolment in an interventional study for depression or participation in such within 30 days of screening * 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.

Outcomes

Primary Outcomes

Regional Cerebral Blood Flow

Changes in cerebral blood flow within three a priori-defined brain regions relevant to mood regulation and depression as assessed by arterial spin labeling acutely at expected peak drug concentration during treatment visits.

Time frame: Up to 3 weeks

Montgomery-Asberg Depression Rating Scale (MADRS) Changes

Changes in the MADRS relative to baseline at study follow-up visits. Higher scores with respect to the MADRS minimum (0) and maximum (60) values represent a worse treatment outcome .

Time frame: Up to 6 weeks

Secondary Outcomes

Functional Network Connectivity

Changes in voxel-wise functional connectivity within four a priori-defined and established functional networks relevant to mood regulation and depression as assessed by resting state functional magnetic resonance imaging acutely at the time of expected peak drug concentration during treatment visits.

Time frame: Up to 3 weeks

17-item Hamilton Depression Rating Scale (GRID-HAMD-17)

Baseline grid-version of the 17-item Hamilton Depression Rating Scale score. The GRID-HAMD is a 17-item clinician-administered rating scale designed to assess severity of depressive symptoms. The score range is 0 to 52, with higher score indicating more severe depression .

Time frame: 24 hours

Incidence of response

Incidence of response, calculated as the proportion of participants with a response (defined as a ≥ 50% improvement in MADRS total score from Baseline) at at follow-up after psilocybin administration.

Time frame: up to 6 weeks

Incidence of remission

Incidence of remission, calculated as the proportion of participants with remission (defined as MADRS total score \<11) at week 3 and 6 following the initial psilocybin/niacin administration.

Time frame: up to 6 weeks

Patient Health Questionnaire 9-item (PHQ-9)

The PHQ-9 will be collected at baseline as well as week 3 and 6 post-psilocybin administration. The PHQ-9 is a self-rated measure of depressive symptom severity in the past two weeks. Each of the nine items is rated on a Likert scale, ranging from 0 (not at all) to 3 (nearly every day), and summed for a total score between 0 (no symptoms) to 27 (most severe).

Time frame: up to 6 weeks

16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR-16)

The QIDS-SR-16 will be collected at baseline as well as week 3 and 6 post-psilocybin administration. The QIDS-SR-16 is a self-report scale with scores that range from 0 to 27. Higher scores indicate greater depression .

Time frame: up to 6 weeks

Columbia Suicide Severity Rating Scale (C-SSRS)

The C-SSRS will be collected at baseline as well as week 3 and 6 post-psilocybin administration. The C-SSRS evaluates suicidal ideation and behaviour. The suicidal ideation score ranges from 0 (no ideation) to 5 (active suicidal ideation with specific plan and intent). Suicidal ideation intensity score ranges from 0 (no ideation) to 25 (most severe). The presence of suicidal behaviour is rated as a binary response; the lethality of previous actual attempts is rated on a scale of 0 (no or very minor physical damage) to 5 (death) and the potential lethality of actual attempts are rated on a scale of 0 (behaviour not likely to result in injury) to 2 (behaviour likely to result in death despite available medical care) .

Time frame: up to 6 weeks

Brief Psychiatric Rating Scale (BPRS)

The BPRS will be collected at baseline as well as week 3 and 6 post-psilocybin administration. The BPRS rating scale has 18 items, each item rated on a severity scale of 1 (not present) to 7 (extremely severe). 0 is entered if the item is not assessed.

Time frame: up to 6 weeks

Sheehan Disability Scale (SDS)

The SDS will be collected at baseline as well as week 3 and 6 post-psilocybin administration. The SDS total score ranges from 0 to 30, with 0 representing no impairment and 30 representing severe impairment. The last two items of the scale (Days Lost and Days Unproductive) range from 0 to 7 (higher number denotes greater impairment) .

Time frame: up to 6 weeks

Generalized Anxiety Disorder-7 (GAD-7)

The GAD-7 will be collected at baseline as well as week 3 and 6 post-psilocybin administration. Scores from 0 ("Not at all") to 3 ("Nearly every day"), and total score ranges from 0 to 21; a higher score denotes greater symptom severity.

Time frame: up to 6 weeks

Snaith-Hamilton Pleasure Scale (SHAPS)

The SHAPS will be collected at baseline as well as week 3 and 6 post-psilocybin administration. The SHAPS is rated on a 4-point Likert scale from 0 ("strongly disagree") to 3 ("strongly agree"). Total score ranges from 14 to 56, wherein a higher score indicates greater hedonic capacity (lower anhedonic severity) .

Time frame: up to 6 weeks

6-Item Clinician Administered Dissociative Symptom Scale (CADSS-6)

The CADSS-6 is a simplified 6-item scale that will be collected at both treatment visits as well as week 3 and 6 post-psilocybin administration. Responses range from 0 ("not at all") to 4 ("extremely"). Total scores range from 0-24, wherein a higher score indicates greater dissociation.

Time frame: up to 6 weeks

Montreal Cognitive Assessment (MoCA)

The MoCA total score will be collected at baseline as well as week 6 (3 weeks after second treatment visit). This is scale is a cognitive screening assessment tool that tests six domains of cognition, with scores ranging from 0-30, wherein a higher score indicates better cognitive performance: 18-25 points ("Mild cognitive impairment"), 10-17 points ("Moderate cognitive impairment"), less than 10 points ("Severe cognitive impairment").

Time frame: up to 6 weeks

Hopkins Verbal Learning Test-Revised (HVLT-R)

The revised HVLT-R total Score will be collected at baseline as well as week 6 (3 weeks after second treatment visit). A list learning test that contains 12 nouns that are read to a participant for three consecutive trials. After each trial, a participant is asked to recall the words that were read to them. The number of words recalled on each trial is summed together to produce a total score. The higher total score equates to a better outcome.

Time frame: up to 6 weeks

CANTAB Rapid Visual Information Processing

We will use the CANTAB software program for evaluating cognitive domains baseline as well as week 6 (3 weeks after second treatment visit). Sustained attention will be measured by the Rapid Visual Information Processing task. Responses will be scored as the number of responses recorded as having occurred within 1800 milliseconds of the final digit presentation for each of the target sequences, with more responses reflecting better sustained attention.

Time frame: up to 6 weeks

CANTAB Reaction Time

We will use the CANTAB software program for evaluating cognitive domains at baseline as well as week 6 (3 weeks after second treatment visit). Psychomotor speed will be measured by the Reaction Time (RTI) task. Simple reaction time will be the outcome of interest, with faster reaction time (lower latency) reflecting better psychomotor speed.

Time frame: up to 6 weeks

CANTAB Spatial Working Memory

The CANTAB software program for evaluating cognitive domains is used at baseline as well as week 6 (3 weeks after second treatment visit). Executive function will be measured by the Spatial Working Memory (RTI) task. This is a search task that stresses executive function and spatial working memory, requiring subjects to use heuristic search strategies. A higher score indicates better performance in spatial working memory.

Time frame: up to 6 weeks

CANTAB One Touch Stockings of Cambridge

We will use the CANTAB software program for evaluating cognitive domains at baseline as well as week 6 (3 weeks after second treatment visit). Executive function will be measured by the One Touch Stockings of Cambridge (OTS) task. This is a spatial planning task that stresses executive function, requiring subjects to use reordered stacked objects to match a presented pattern. Fewer 'moves' indicates better executive function.

Time frame: up to 6 weeks

CANTAB Delayed Matching to Sample

We will use the CANTAB software program for evaluating cognitive domains at baseline as well as week 6 (3 weeks after second treatment visit). Memory will be measured by the Delayed Matching to Sample (DMS) task. This is a memory task that stresses encoding, requiring subjects to remember and differentiate complex patterns when presented after a delay. More correct responses, or greater accuracy, reflects better memory.

Time frame: up to 6 weeks

CANTAB Paired-Associates Learning

We will use the CANTAB software program for evaluating cognitive domains at baseline as well as week 6 (3 weeks after second treatment visit). Memory will be measured by the Paired-Associates Learning (PAL) task. This is a memory task =sensitive to changes in functioning of the medial temporal lobe, requiring subjects to remember and identify previous locations of complex patterns when presented after a delay. More correct responses, or greater accuracy, reflects better memory.

Time frame: up to 6 weeks

CANTAB Emotion Recognition Task

We will use the CANTAB software program for evaluating cognitive domains at baseline as well as week 6 (3 weeks after second treatment visit). Social/emotional cognition will be assessed by the Emotion Recognition Task (ERT). Subjects are briefly shown faces morphed to display various emotions of varying intensities, and then required to identify the emotion. Better accuracy defined as number of correct responses reflects better emotional cognition.

Time frame: up to 6 weeks

Revised Mystical Experience Questionnaire (MEQ30)

The MEQ30 is a validated self-report revised 30-item questionnaire recording elements that comprise the mystical experience. 0 ("none (not at all)") to 5 ("extreme (more than any other time in my life and stronger than 4)"), with a total scoring range from 0 to 150. Higher scores indicate a more profound mystical experience.

Time frame: up to 8 weeks

Persistent Effects Questionnaire (PEQ)

The PEQ is a non-validated self-report 145-item questionnaire that describe any changes in the participants' lives that may be attributed to the psilocybin treatment. Comprises of 6 categories with items rated on a 6-point scale from 0 ("none") to 5 ("extreme"). Higher scores indicate a greater magnitude of the persistent effects following their psilocybin experience.

Time frame: 24 hours

A Randomized Neuroimaging Trial of Psilocybin in Depression

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts