The Safety and Efficacy of Psilocybin in... — Clinical Trial Details

Phase II interventional

Randomized, quadruple Blind

Randomized, parallel-group, quadruple-blind, dose-ranging Phase II trial of psilocybin for treatment-resistant depression with three experimental dose arms (low, medium, high); psychotherapy provided alongside dosing.

Multi-centre study (sites in the United States, Canada and several European countries) assessing safety and efficacy outcomes in adults with TRD; actual enrolment reported as 233.

Study Protocol

Preparation

sessions

Dosing

sessions

Kadima Neuropsychiatry Institute — La Jolla, California, United States

Altman Clinical and Translational Research Institute, University of California — San Diego, California, United States

Stanford Department of Psychiatry — Stanford, California, United States

Mood and Anxiety Disorders Program Emory University School of Medicine — Atlanta, Georgia, United States

Ray Worthy Psychiatry LLC — New Orleans, Louisiana, United States

Sheppard Pratt Health System — Baltimore, Maryland, United States

New York State Psychiatric Institute — New York, New York, United States

UT Center of Excellence on Mood Disorders, University of Texas Health Science Center — Houston, Texas, United States

Canadian Rapid Treatment Centre of Excellence — Mississauga, Ontario, Canada

Centre for Addiction and Mental Health — Toronto, Ontario, Canada

National Institute of Mental Health Czech Republic — Klecany, Czechia

Enhed for Psykiatrisk Forskning, Psykiatrien i Aalborg — Aalborg, Denmark

Charité - Universitätsmedizin Berlin, Department of Psychiatry and Psychotherapy, Campus Benjamin Franklin — Berlin, Germany

Tallaght University Hospital — Dublin, Ireland

Groningen University Medical Centre

Participants meeting all the following inclusion criteria at Screening (V1) should be
considered for admission into the study
1. Signed ICF.
2. 18 years of age or older at Screening (V1).
3. At least moderate MDD (single or recurrent episode as informed by DSM-5; if single episode, duration of ≥ 3 months and ≤ 2 years) based on medical records, clinical assessment and documented completion of the version 7.0.2 MINI.
4. HAM-D-17 (17-item) score ≥ 18 at Screening (V1) and at Baseline (V2).
5. Failure to respond to an adequate dose and duration of 2, 3, or 4 pharmacological treatment for the current episode as determined through the MGH-ATRQ and using the supplementary advice on additional antidepressants not included in MGH-ATRQ (Appendix III). Augmentation with an add-on treatment counts as a second treatment, provided it is approved for the adjunctive treatment of MDD in that country.
6. McLean Screening Instrument for Borderline Personality Disorder < 7 at
Screening (V1).
7. Have successfully discontinued all antidepressant medications at least 2 weeks prior to Baseline (V2).
8. Ability to complete all protocol required assessment tools without any assistance or alteration to the copyrighted assessments, and to comply with all study visits.

Participants meeting any of the following exclusion criteria at Screening (V1) will not be enrolled in the study.
Psychiatric Exclusion Criteria:
1. Current or past history of schizophrenia, psychotic disorder (unless substance induced or due to a medical condition), bipolar disorder, delusional disorder, paranoid personality disorder, schizoaffective disorder, borderline personality disorder, or any serious psychiatric comorbidity as assessed by medical history and a structured clinical interview (version 7.0.2 MINI).
2. Prior electroconvulsive therapy and/or ketamine for current episode.
3. Current cognitive behavioural therapy (CBT) that will not remain stable for the duration of the study. CBT cannot be initiated within 21 days of baseline.
4. Current (within the last year) alcohol or substance abuse as informed by DSM-5 at Screening (V1).
5. Significant suicide risk as defined by (1) suicidal ideation as endorsed on items 4 or 5 on the C-SSRS within the past year, at Screening or at Baseline, or;
(2) suicidal behaviors within the past year, or; (3) clinical assessment of significant suicidal risk during subject interview.
6. Depression secondary to other severe medical conditions.
7. Other personal circumstances and behaviour judged to be incompatible with establishment of rapport or safe exposure to psilocybin, including exposure to psilocybin within the past year and use of psychedelics, such as ayahuasca, during the current depressive episode.
General Medical Exclusion Criteria:
8. Women who are pregnant, nursing, or planning a pregnancy. Participants who are sexually active must agree to use a highly effective contraceptive method throughout their participation in the study. Women of child bearing potential must have a negative urine pregnancy test at Screening (V1) and Baseline (V2).
9. Cardiovascular conditions: recent stroke (< 1 year from signing of ICF), recent myocardial infarction (< 1 year from signing of ICF), hypertension (blood pressure > 140/90 mmHg) or clinically significant arrhythmia within 1 year of signing the ICF.
10. Uncontrolled insulin-dependent diabetes.
11. Seizure disorder.
12. Positive urine drug screen for illicit drugs or drugs of abuse at V1 and/or V2. 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 in conjunction with the medical monitor.
13. Current enrolment in any investigational drug or device study or participation in such within 30 days of Screening (V1).
14. Current enrolment in an interventional study for depression or participation in such within 30 days of Screening (V1).
15. Abnormal and clinically significant results on the physical examination, vital signs, ECG, or laboratory tests at Screening (V1).

Start: 2019-01-01

End: 2021-09-27

Ekaterina Malievskaia

Leiden University Medical Centre — Leiden, Netherlands

Utrecht University Medical Centre — Utrecht, Netherlands

Unidade de Neuropsiquiatria, Centro Clinico Champalimaud — Lisbon, Portugal

Hospital de Dia Numancia — Barcelona, Spain

Institute Hospital del Mar of Medical Research (IMIM) — Barcelona, Spain

Clinical Research and Imaging Centre — Bristol, Avon, United Kingdom

Wolfson Research Centre, Campus for Ageing and Vitality — Newcastle upon Tyne, Tyne and Wear, United Kingdom

St. Pancras Clinical Research — London, United Kingdom

Kings College London, Institute of Psychiatry, Psychology and Neurology — London, United Kingdom

Greater Manchester Mental Health Foundation Trust — Manchester, United Kingdom

Company

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The Safety and Efficacy of Psilocybin in Participants With Treatment Resistant Depression

Detailed Description

Study Protocol

Preparation

Dosing

Locations

Related Publications

Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression

Integration

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Study Arms & Interventions

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Interventions

Medium dose

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High dose

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Participants

Inclusion Criteria

Exclusion Criteria

Study Details

Study Team

Sponsors & Collaborators

Investigators

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The Impact of Antidepressant Discontinuation Prior to Treatment with Psilocybin for Treatment-Resistant Depression

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Results From a Long-Term Observational Follow-Up Study of a Single Dose of Psilocybin for a Treatment-Resistant Episode of Major Depressive Disorder

The Relationship Between Participant Pretreatment Clinical Presentation and the Quality of Psilocybin Experience: A Retrospective Analysis

The role of therapeutic alliance in psilocybin treatment for treatment-resistant depression: A post hoc path analysis