Major depressive disorder Mental and Behavioural Disorders
Conditions
Interventions
This adaptive design clinical trial is to be conducted in two parts:
Part 1 is a phase IIa, open-label, multiple-ascending dose, dose-finding study to assess the safety, cardiovascular effects, pharm
Sponsors
Clerkenwell Health
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Aged 18 years and above 2. Male or female 3. DSM-5 defined MDD with partial response SSRI monotherapy (HAM-D score >17) or no response 4. Able to communicate well in English and follow study procedures 5. Any history of suicide attempts/suicidal ideation; the subject scores 'yes' on item 4 or 5 of the Suicidal Ideation section of the Columbia Suicidality Scale Scoring if this ideation occurred in the past 12 months, or 'yes' on any item of the Suicidal Behaviour Section, and the opinion of the investigator 6. Medically suitable as determined by screening including a personal interview, a medical questionnaire, a physical examination, an electrocardiogram (ECG), and blood tests 7. Currently taking a first course of SSRI antidepressant treatment for at least 8 weeks
Exclusion criteria
Exclusion criteria: 1. Treatment with any other antidepressant medication other than the currently prescribed SSRI antidepressant 2. Current or past diagnosis of schizophrenia, psychotic disorder, bipolar disorder I and II, delusional disorder, paranoid personality disorder, schizoaffective disorder, borderline personality disorder, or judged to be incompatible with establishment of rapport or safe exposure to psilocybin, as assessed through medical history and the Mini International Neuropsychiatric Inventory (MINI) 3. Family history of schizophrenia, schizoaffective disorder, or bipolar affective disorder 4. Anyone on a research study of an investigational drug or who has been on a clinical trial within 1 month of enrollment 5. Scores from the screener and baseline Columbia Suicide Severity Rating Scale (C-SSRS) that indicate that the participant is of clinically significant risk of suicide. A decision will be formed based on C-SSRS scores and used in combination with other clinically significant data at screening and baseline. Judged to be of high suicide or self-harm risk following psychological assessment at screening or baseline. 6. Currently receiving psychotherapy other than that which forms far this study 7. Current (140/90 mmHg) or clinically significant arrhythmia within 1 year of IC 4. Anyone who, at screening, has clinically significant findings on physical examination, including vital signs (HR below 60 or above 100 bpm, blood pressure below 90/60 or above 140/90), ECG (ST greater than 450 msec), and positive alcohol breath test 5. An estimated glomerular filtration rate (eGFR) of <45 ml/min/1.73 m² 6. Results falling above 2.5 times the upper reference level on alanine aminotransferase 0-45 IU/L, aspartate aminotransferase 0-50 IU/L, gamma-glutamyl transferase 0-70 IU/L (male), 0-40 IU/L (female) 7. Results falling above 1.5 times the upper reference level on bilirubin 3-20 µmol/L 8. Results falling above 1.0 times the upper reference level on conjugated bilirubin 0-14 µmol/L 9. Results falling above 1.0 times the upper reference level on alkaline phosphatase 90-300 IU/L 10. Any clinically significant renal, pulmonary, gastrointestinal, hepatic, or other illness that could affect the interpretation of results or be a potential health risk for the person if they were to be included in the study 11. Below 16 or above
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part 1: adverse events and changes in cardiovascular parameters (HR, BP, and QTc) that raise a safety concern such as a hypertensive crisis (systolic BP >160 mmHg or diastolic BP >110 mmHg), a QTc prolongation >20 msec, any signs or symptoms or serotonin syndrome, or any other adverse event that in the opinion of the investigator should preclude that patient from further dosing. Adverse events and changes in cardiovascular parameters will be collected from informed consent until the completion of the final follow-up visit. Part 2: Changes in depression symptoms as measured by scores on the Montgomery-Åsberg Depression Rating Scale (MADRS) at 4-weeks post baseline. | — |
Secondary
| Measure | Time frame |
|---|---|
| Part 1: 1. Psilocin plasma concentrations at 20, 40, 60, 80, 120, 3 4, 6, 8, 24 h after dose 2. Subjective psychedelic intensity as measured on a 1-10 scale at 20, 40, 60, 80, 120 min, 3, 4, 6, 8 h after dose 3. Sub-acute cognitive effects as measured by the Brief experiential avoidance questionnaire (BEAQ) at baseline, 7 days, and 6 weeks post the last dose 4. Sub-acute cognitive effects as measured by the Psychological flexibility (Psy-flex) at baseline, 7 days, and 6 weeks post the last dose 5. Sub-acute cognitive effects as measured by the Mindful attention awareness scale (MAAS) at baseline, 7 days, and 6 weeks post the last dose 6. Sub-acute cognitive effects as measured by the BDNF at baseline, 0, 40, 60, 80, 120 min, 3, 4, 6, 8, 24 h after dose 7. Changes in depression symptoms measured by Beck’s Depression Inventory (BDI) at baseline, 7 days, and 6 weeks post the last dose 8. Patient impression of improvement as measured by the Patient’s Global Impression of Change (PGIC) at 7 days and 6 weeks post the last dose 9. The effect of on emotional breakthrough as measured by the Emotional Breakthrough Inventory (EBI) during each dosing session 10. The dose response relationship and correlations between the secondary endpoints Part 2: 1. Changes in depression symptoms as measured by scores on the Montgomery-Åsberg Depression Rating Scale (MADRS) at baseline, week 4 & week 8 2. Changes in biomarkers as measured by BDNF at baseline, 0 min, 60 min, 3 h, and 6 h after drug administration 3. Adverse events from informed consent to completion of final follow-up 4. Sub-acute cognitive changes as measured by the Brief experiential avoidance questionnaire (BEAQ) at baseline, week 4 & week 8 5. Sub-acute cognitive changes as measured by the Psychological flexibility (Psy-Flex) at baseline, week 4 & week 8 6. Sub-acute cognitive changes as measured by the Mindful attention awareness scale (MAAS) at baseline, week 4 & week 8 7. Patient impression of improvemen | — |
Countries
United Kingdom
Contacts
Public ContactClare Knight
Outcome results
None listed