Clinical trial NCT05029466: Psilocybin for Treatment-Resistant Depression
Official title: The Efficacy and Tolerability of Psilocybin in Participants With Treatment-Resistant Depression: a Phase 2, Randomized Feasibility Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Treatment Resistant Depression
Keywords: Bipolar II Disorder
Major Depressive Disorder
Depressive Disorder, Treatment-Resistant
Mood Disorders
Mental Disorders
Psilocybin
Hallucinogen
Psychedelic
Antidepressant
Phase 2
Depression
Lead sponsor: Brain and Cognition Discovery Foundation
Sponsor class: OTHER
Collaborators: name: Braxia Scientific Corp.
name: Usona Institute
First posted: 2021-08-31
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to see if psilocybin, an investigational drug, is safe and well tolerated. Researchers also want to know if psilocybin can improve symptoms of depression. This study will see if psilocybin is safe and well tolerated by tracking changes in suicidal thoughts and behaviour, monitoring if any participants choose to stop participating in the study, and measuring any serious side effects, as well as how long they take to resolve. This study will also see if depression symptoms improve (or worsen) after psilocybin is administered. Additional information about participants' depressive symptoms and side effects will also be measured during the study.

Detailed description: This randomized clinical trial will assess the feasibility, safety, and efficacy of single and repeat doses of psilocybin at point-of-care in persons with treatment-resistant depression as part of major depressive disorder or bipolar II disorder. The primary objective is to evaluate the feasibility of psilocybin in adults with treatment-resistant depression. The secondary objectives are to assess the efficacy and tolerability of psilocybin at point-of-care.

Eligibility criteria: Inclusion Criteria:

1. Over the age of 18 years and under the age of 65;
2. Diagnosed with major depressive disorder or bipolar II disorder by a healthcare provider;
3. Experiencing a major depressive episode (MDE) without psychotic features as defined and operationalized in the DSM-5, where the duration of the current episode is at least 3 months;
4. Have failed to respond to an adequate dose and duration of at least two guideline-concordant pharmacological treatments for the current MDE, as determined by the Massachusetts General Hospital-Antidepressant Treatment History Questionnaire; and
5. Able to complete all protocol required assessment tools without any assistance or alteration to the copyrighted assessments, and to comply with all study visits.

Individuals meeting one or more of the following DSM-5-defined criteria will be excluded:

* Current or past history of bipolar I disorder, schizophrenia, psychotic disorder, delusional disorder, paranoid personality disorder, or schizoaffective disorder, as assessed by a structured clinical interview (MINI) and International Personality Disorder Examination (IPDE);
* First degree history of schizophrenia or any psychotic disorders, including bipolar disorder with psychotic features;
* Currently experiencing symptoms of hypomania or mania as measured by the Young Mania Rating Scale (YMRS) total score \> 12;
* History of a hypomanic or manic episode in the past 3 months;
* History of substance use and/or alcohol use disorder, of moderate severity or greater, in the past 3 months;
* Lifetime history of substance use disorder with a hallucinogen;
* Lifetime history of substance-induced psychosis;
* Currently experiencing psychotic symptoms as part of an MDE (mood congruent/mood incongruent).

Individuals meeting one or more of the following criteria will also be excluded:

* Exposure to psilocybin or any other psychedelic in the past 12 months prior to screening and/or during the current MDE;
* Uncontrolled or insulin-dependent diabetes;
* Seizure disorder;
* Other personal circumstances or behaviour 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;
* Refusal to use an effective contraceptive method by the participant or participant's partner (i.e., combined estrogen- and progestogen-containing hormonal contraception or progestogen-only hormonal contraception with inhibition of ovulation; intrauterine device; intrauterine hormone-releasing system; bilateral tubal occlusion; vasectomized partner; sexual abstinence) throughout their participation in the study;
* Recent stroke (\< 1 year from signing of ICF), 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;
* 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);
* Current enrolment in any investigational drug or device study or participation in such within 30 days of screening;
* Current enrolment in an interventional study for depression or participation in such within 30 days of screening;
* Abnormal and clinically significant results on the physical examination, vital signs, ECG, or laboratory tests at 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: Feasibility of the study based on participant retention
timeFrame: Up to 24 weeks
measure: Feasibility of the study based on suicidal ideation and behaviour scores
timeFrame: Up to 24 weeks
measure: Feasibility of the study based on adverse events
timeFrame: Up to 24 weeks
Secondary outcomes:
measure: Montgomery-Åsberg Depression Rating Scale (MADRS) total score
timeFrame: Up to 24 weeks
measure: Montgomery-Åsberg Depression Rating Scale (MADRS) response rate
timeFrame: Up to 24 weeks
measure: Montgomery-Åsberg Depression Rating Scale (MADRS) remission rate
timeFrame: Up to 24 weeks
measure: McIntyre and Rosenblat Rapid Response Scale (MARRRS)
timeFrame: Up to 24 weeks
measure: Patient Health Questionnaire 9-item (PHQ-9)
timeFrame: Up to 24 weeks
measure: Clinical Global Impressions Scale (CGI)
timeFrame: Up to 24 weeks
measure: Quick Inventory for Depressive Symptomatology, Self-Report, 16-item (QIDS-SR-16)
timeFrame: Up to 24 weeks
measure: Columbia Suicide Severity Rating Scale (CSSRS)
timeFrame: Up to 24 weeks
measure: Clinician-Administered Dissociative States Scale (CADSS), 23-item
timeFrame: Up to 20 weeks
measure: Clinician-Administered Dissociative States Scale (CADSS), 6-item
timeFrame: Up to 20 weeks
measure: Brief Psychiatric Rating Scale (BPRS)
timeFrame: Up to 20 weeks
measure: Young Mania Rating Scale (YMRS)
timeFrame: Up to 20 weeks
measure: Mystical Experiences Questionnaire (MEQ)
timeFrame: Up to 20 weeks
measure: Sheehan Disability Scale (SDS)
timeFrame: Up to 24 weeks
measure: EuroQol-5D 5-Level (EQ-5D-5L)
timeFrame: Up to 24 weeks
measure: World Health Organization-5 Well-Being Index (WHO-5)
timeFrame: Up to 24 weeks
measure: World Productivity and Impairment Questionnaire (WPAI)
timeFrame: Up to 24 weeks
measure: Perceived Deficits Questionnaire - Depression - 5-Item (PDQ-5-D)
timeFrame: Up to 24 weeks
measure: Digit Symbol Substitution Test (DSST)
timeFrame: Up to 24 weeks
measure: Trail Making Test A (TMT-A)
timeFrame: Up to 24 weeks
measure: Trail Making Test B (TMT-B)
timeFrame: Up to 24 weeks
measure: Generalized Anxiety Disorder-7 (GAD-7)
timeFrame: Up to 24 weeks
measure: Snaith-Hamilton Pleasure Scale (SHAPS)
timeFrame: Up to 24 weeks
measure: Peripheral inflammatory and metabolic biomarkers
timeFrame: Up to 2 weeks
Other outcomes:
Locations:
city: Mississauga
country: Canada
facility: Canadian Rapid Treatment Centre of Excellence (CRTCE)
state: Ontario
Study officials:
affiliation: Canadian Rapid Treatment Centre of Excellence
name: Joshua D Rosenblat, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References: