Psilocybin in Depression Resistant to Standard Treatments (PsiDeR)

A Randomised, Placebo Controlled Trial of Psilocybin in Treatment Resistant Depression: A Feasibility Study

A single centre clinical trial to evaluate the feasibility, safety and efficacy of psilocybin, given under supportive conditions, in a randomised, blinded design in adult participants with treatment resistant major depressive disorder. The primary objective is to evaluate feasibility by measuring recruitment rates, dropout rates and by estimating the variance of the primary outcome measure (MADRS).

Study Overview

• Status: Recruiting
• Conditions: Treatment Resistant Depression
• Intervention / Treatment: Combination product: Psilocybin assisted therapy; Combination product: Placebo assisted therapy

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: James Rucker; Phone Number: +442032991851; Email: kingscrf@kcl.ac.uk

Study Locations

• United Kingdom
  • London, United Kingdom, SE5 9RS
    • Recruiting
    • Clinical Research Facility, King's College Hospital
    • Contact: James Rucker, MD; Phone Number: +442032991851; Email: kingscrf@kcl.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 25 - 80 years
• Fluent in the English language
• Fulfil Diagnostic and Statistical Manual of Mental Disorders (5th Edition) (DSM-5) criteria for a primary diagnosis of current single or recurrent episodes of MDD of at least moderate severity but without psychotic features as defined on the MINI 7.0. Positive and primary diagnoses on the MINI 7.0 will be subject to confirmation at clinical interview by a psychiatrist.
• 17-item HAM-D score ≥ 14.
• Have failed to respond to 2 or more antidepressants prescribed at the minimum effective dose for at least 6 weeks OR at least 1 antidepressant prescribed at the minimum effective dose for at least 6 weeks AND a course of evidence-based psychotherapy given for at least 6 sessions.
• For those aged ≥ 60 years, the first episode of depression must have started prior to their 60th birthday.

Exclusion Criteria:

• Diagnosis of bipolar disorder (defined as meeting DSM-5 criteria for bipolar 1 or bipolar 2) on the MINI 7.0. Positive diagnoses on the MINI will be subject to confirmation at clinical interview by a psychiatrist.
• Diagnosis of psychotic disorder (defined as meeting DSM-5 criteria for any psychotic disorder) on the MINI 7.0, EXCEPT substance/medication induced psychotic disorder where the duration was limited to the acute period of direct intoxication with the substance/medication. Positive diagnoses on the MINI will be subject to confirmation at clinical interview by a psychiatrist.
• Diagnosis of drug or alcohol dependence syndrome (defined as meeting DSM-5 criteria for any dependence syndrome) on the MINI 7.0. Positive diagnoses on the MINI will be subject to confirmation at clinical interview by a psychiatrist.
• Diagnosis of any personality disorder (defined as meeting DSM-5 criteria for any personality disorder) based on clinical interview and the MINI 7.0. Positive diagnoses on the MINI will be subject to confirmation at clinical interview by a psychiatrist.
• Diagnosis of any dementia (defined as meeting DSM-5 criteria for any dementia disorder) based on clinical interview by a psychiatrist.
• Personal history of a ≥ 1 suicide attempt in the past year requiring hospitalization, defined using the CSSRS (Q6 (past year) = "y") and clinical interview with a psychiatrist.
• Other personal circumstances and behaviour judged to be incompatible with establishment of rapport or safe exposure to psilocybin.
• Depression secondary to other medical conditions
• Medical diagnosis incompatible with psilocybin treatment
• Inability to provide a screening blood sample, urine sample or electrocardiogram.
• Biochemical abnormalities (defined as falling outside the normal reference range) as evaluated by a full blood count, full biochemistry profile and thyroid function tests. Biochemical abnormalities must also be determined as clinically significant by a medical doctor to fulfil the criterion for exclusion.
• Electrocardiographic abnormalities, defined as any abnormality that is not normal sinus rhythm and determined as clinically significant by a medical doctor.
• Women of child bearing potential not using adequate contraception.
• Pregnant or breast-feeding women.
• Those unable to give informed consent.
• Non-registration with a GP or failure to consent to sharing of the GP summary care record and any psychiatric assessments held.
• Those enrolled in another drug trial
• Hypersensitivity to the IMP or to any of the excipients or placebo

Exclusions for Pre-Existing Medical Conditions

Participants will be excluded if they have a current diagnosis of ≥1 of:

• Uncontrolled diabetes
• Hypertension (defined as a systolic blood pressure ≥ 160mm/Hg or a diastolic blood pressure ≥ 100mm/Hg on three separate readings). All readings of systolic blood pressure ≥ 140mm/Hg or diastolic blood pressure ≥ 90mm/Hg will be reviewed by a clinician. Hypertension ascertained prior to dosing will be subject to clinical confirmation via collateral information from the GP or other source.
• Cardiac failure, defined as class IV of the New York Heart Association classification
• Renal failure, defined as ≥ stage 4 (GFR ≤ 29mL/min)
• Liver failure, defined as a clinical diagnosis of liver fibrosis, cirrhosis of the liver, liver failure or advanced liver disease.
• Any cardiac arrhythmia, except atrial fibrillation.
• Any form of epilepsy

Past diagnosis of ≥1 of:

• Cerebrovascular accident or intracerebral trauma.
• Myocardial infarction within 1 year prior to the screening visit.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Psilocybin 25mg PO	Combination product: Psilocybin assisted therapy; A package of psychological therapy and a single dosing session of psilocybin.
Placebo Comparator: Placebo PO	Combination product: Placebo assisted therapy; A package of psychological therapy and a single dosing session of placebo.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Montgomery Asberg Depression Rating Scale	Investigator rated depression scale	3 weeks from baseline. Lower score is a better outcome.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quick Inventory of Depressive Symptoms SR 16	Participant rated depression scale	3 weeks from baseline. Lower score is a better outcome.

Collaborators and Investigators

• Sponsor: King's College London
• Collaborators: South London and Maudsley NHS Foundation Trust
• Investigators: Principal Investigator: James Rucker, MD PhD, King's College London

Publications and helpful links

General Publications

• Rucker J, Jafari H, Mantingh T, Bird C, Modlin NL, Knight G, Reinholdt F, Day C, Carter B, Young A. Psilocybin-assisted therapy for the treatment of resistant major depressive disorder (PsiDeR): protocol for a randomised, placebo-controlled feasibility trial. BMJ Open. 2021 Dec 1;11(12):e056091. doi: 10.1136/bmjopen-2021-056091.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2020
• Primary Completion (Anticipated): September 1, 2023
• Study Completion (Anticipated): November 1, 2023

Study Registration Dates

• First Submitted: July 1, 2021
• First Submitted That Met QC Criteria: July 1, 2021
• First Posted (Actual): July 13, 2021

Study Record Updates

• Last Update Posted (Actual): July 22, 2021
• Last Update Submitted That Met QC Criteria: July 15, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Treatment-Resistant; Physiological Effects of Drugs; Psychotropic Drugs; Hallucinogens; Psilocybin
• Other Study ID Numbers: 252750

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No