Major depressive disorder MedDRA version: 21.1 Level: PT Classification code 10057840 Term: Major depression System Organ Class: 10037175 - Psychiatric disorders
Conditions
Interventions
Product Name: Psilocybin
Pharmaceutical Form: Capsule
INN or Proposed INN: Psilocybin
CAS Number: 520-52-5
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharma
Sponsors
King's College London
South London & Maudsley NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
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. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 60 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 60
Exclusion criteria
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 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 tr
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the feasibility of a randomised, controlled trial design, in which a single dose of psilocybin 25mg PO vs placebo, is given to adult participants with treatment resistant major depressive disorder (TRD), under psychologically supportive conditions, with 6 weeks of follow up, by measuring recruitment rates, dropout rates and by estimating the variance of the primary outcome measure (MADRS) to inform upon the design of a phase 3 trial.;Secondary Objective: 1)To assess the clinician-rated efficacy of psilocybin 25mg compared to placebo via: a)The change in the MADRS total score from Baseline to 3 weeks after treatment b)The proportion of participants who demonstrate a response to treatment( =50% decrease in MADRS total score) from Baseline to Week 3. c)proportion of participants in remission( MADRS total score =10 at Week 3) 2)To assess the participant-rated efficacy of psilocybin 25mg compared to placebo via: a)proportion of participants who demonstrate a response to treatment, ( a =50% decrease in QIDS-SR-16 total score) from Baseline (V2) to Week 3 (V6). b)proportion of participants in remission, where remission is defined as a QIDS-SR-16 total score =5 at Week 3. 3)To evaluate the safety and tolerability of psilocybin in participants with TRD based on adverse events (AEs), changes in vital signs and suicidal ideation/behaviour (measured using the Columbia Suicide Severity Rating Scale). ;Primary end point(s): Recruitment rates, dropout rates and estimation of the variance of the primary outcome measure (MADRS). ;Timepoint(s) of evaluation of this end point: 3 weeks after dosing | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) The change in the Montgomery-Asberg Depression Rating Scale total score from the Baseline Visit (V2 - 1 day prior to treatment) to Week 3 after treatment (V6). 2) The proportion of participants who demonstrate a response to treatment, where response to treatment is defined as a =50% decrease in MADRS total score from Baseline to Week 3. 3) The proportion of participants in remission, where remission is defined as a MADRS total score =10 at Week 3. 4) The proportion of participants who sustain a response up to Week 6, where response is defined as those with =50% decrease in MADRS total score on or before Week 3 and remaining at Week 6. 5) Time to event measures: restart antidepressant medication for any reason, restart medication for continuing depressive symptoms or relapse from a previously recovered state (clinical judgement, supported by the QIDS-SR-16). Participants who withdraw from the study will be censored from the time to event analysis. Exploratory endpoints: 1) Change from baseline (V2) in the following outcome measures a) The WSAS at week 6 (V7) b) The QIDS-SR-16 at week 3 (V6) c) The GAD-7 at week 3 (V6) ;Timepoint(s) of evaluation of this end point: As above | — |
Countries
United Kingdom
Contacts
Public ContactProf. Allan Young
King's College London
Outcome results
None listed