None listed
Conditions
Brief summary
MicroDep is an investigator-initiated trial evaluating the safety and efficacy of low doses of psilocybin as a treatment for depression of moderate severity. We aim to recruit 293 participants to a 6week randomised, placebo controlled trial comprising 11 dosing sessions. Participants will be assessed at baseline, at week 6, and at 1-week and 1-month followup. The primary outcome measure will be the GRID-Hamilton Depression Rating Scale. Secondary outcomes include psychological measures, neurophysiological measures, and omics-based biomarkers. There will be a neuroimaging substudy that will investigate markers of neuroplasticity in 80 participants. We hypothesise that low doses of psilocybin administered over a 6 week period will be superior to placebo in improving clinical outcomes in moderate depression. If we find evidence of efficacy in the main stage, participants randomised to the placebo condition will be offered the opportunity to repeat the intervention with the active drug.
Interventions
The MicroDep trial will investigate a course of low dose psilocybin as a treatment for major depressive disorder of moderate severity.
The experimental drug is 4mg WP001 (psilocybin) capsules, taken orally. Participants will complete a screening and baseline visit, followed by a six week intervention. The intervention will consist of 11 doses, administered every 3-4 days. Doses will be taken on site and adherence will be confirmed by trial staff. Following the intervention participants will comp
The MicroDep trial will investigate a course of low dose psilocybin as a treatment for major depressive disorder of moderate severity. The experimental drug is 4mg WP001 (psilocybin) capsules, taken orally. Participants will complete a screening and baseline visit, followed by a six week intervention. The intervention will consist of 11 doses, administered every 3-4 days. Doses will be taken on site and adherence will be confirmed by trial staff. Following the intervention participants will complete study endpoint, 1-week and 1-month followup visits. Participants will attend the trial site for all study visits. Participants will be monitored by a psychiatrist throughout the trial and may be titrated down to 2mg if they show any signs of impairment. There will also be a neuroimaging substudy, which will recruit a maximum of 80 participants. Participants in this substudy will complete an magnetoencephalography (MEG) scan at baseline and during the first dosing visit. MEG scans are non-invasive. Participants will be asked to lie the scanner while responding to audio and visual cues via a response button. Every third participant will be invited to take part in the neuroimaging study. If a participant declines to take part, the subsequent participant will be invited to the substudy. Any deviation from protocol will be documented.
Sponsors
Macquarie University
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Participants may be included in the study if they meet all of the following inclusion criteria. 1. Age greater than or equal to 18 years at the time of screening 2. Self-reported fluency in English 3. Meets the definition of moderate depression, defined as a score of between 15 and 23 on the Hamilton Rating Scale for Depression 4. Diagnosis of major depressive disorder, as assessed by the Mini International Neuropsychiatric Interview (MINI) 5. Able to swallow WP001 or Caffeine capsules 6. Has a body weight between 50kg and 120kg, and BMI above 16. 7. Refrains from the use of any psychoactive medication not approved by the research team from baseline through Study Termination. 8. Agrees to abstain from herbal, complementary or over the counter medications with serotonergic effects including, but not limited to, St John’s Wort, S-adenosyl methionine (SAM-e), 5-hydroxytryptophan (5-HTP) and L-tryptophan. 9. Agrees to comply with contraception requirements: a. Women of childbearing potential must have a negative urine or serum pregnancy test at screening and baseline and be non-lactating. During the study, women of childbearing potential must agree to use a highly effective method of birth control up to 7 days after the last dose. b. Male participants must agree to use highly effective method of birth control during the participation in the study up to 7 days after the last dose. 10. Able and willing to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations and other study procedures 11. Agrees to study investigators communicating directly with all of their External Health Practitioners. 12. Provides a contact (relative, spouse, close friend or other Support Person) who is willing and able to be reached by the investigators in the event of a participant becoming unreachable. 13. Must agree not to operate heavy machinery, any motorised vehicle or perform tasks that might endanger oneself or others, such as those requiring fine motor control, fast response times or real-time planning for three hours following each dosing session.
Exclusion criteria
Participants will be excluded from the study if they meet any of the following exclusion criteria: 1. Recently started new psychological therapies and/or sessions with health professionals within 30 days of consent (such as counsellor, psychotherapists). Participants with a stable regimen may be included in this study if they agree to continue with the psychological therapies and/or counselling sessions as is (frequency of the therapy and/or sessions should not change) 2. Use of antidepressant or antipsychotic medication in the prior 3 months, or plans to start new antidepressant or antipsychotic medication in the upcoming 2 months 3. Current diagnosis of psychotic disorder, bipolar disorder, personality disorder, post-traumatic stress disorder, or substance use disorders. 4. Identification of a primary mental health diagnosis apart from Major Depressive Disorder on the Mini International Neuropsychiatric Interview. 5. Any participant presenting current serious suicide risk, as determined through psychiatric interview, responses to Columbia Suicide Severity Rating Scale (C-SSRS), and clinical judgment of the investigator will be excluded. Any participant who is likely to require hospitalisation related to suicidal ideation and behaviour, in the judgment of the investigator, will not be enrolled. Any participant presenting with the following on the screening C-SSRS will be excluded: 1. Suicidal ideation score of 4 or greater within the last month of the assessment at any frequency. 2. Suicidal ideation score of 4 or greater within the last 12 months of the assessment at a frequency of once a month or more. 3. Any suicidal preparatory acts or preparatory behaviour, within the last 12 months of the assessment. Participants with non-suicidal self-injurious behaviour may be included if approved by the CI. 4. Any suicidal behaviour, including actual, aborted, or interrupted suicide attempts within lifetime. 5. Would present a serious risk to others as established through clinical interview and contact with External Health Practitioners. 6. Require ongoing concomitant therapy with a psychiatric medication for management. 6. Poorly controlled hypertension or other cardiac abnormalities. 7. History of psychosis, bipolar disorder, stroke, epilepsy, brain injury or head trauma. 8. History of serious liver (Child-Pugh B or C), kidney disease (eGFR<60ml/min). 9. First degree relative with psychotic disorder. 10. Pregnant, or trying to get pregnant, or breastfeeding 11. Use of any psychotropic drug (excluding alcohol, nicotine and caffeine) within the last 3 months from date of consent 12. Moderate to severe cannabis or alcohol use disorder in the prior 12 months 13. An illicit or prescription drug use disorder of any severity in the prior 12 months 14. Baseline 12-lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results 15. Significantly abnormal laboratory blood test defined as outside the normal range and deemed clinically significant by an investigator with expertise in this field 16. Resting blood pressure exceeding 160mmHg systolic and 100mmHg diastolic 17. Currently taking part in another clinical trial involving interventions such as an investigational drug, device, or psychotherapy 18. Current evidence of, or a history of, any condition, therapy or abnormal laboratory assessment or other events that, in the opinion of the investigator, may affect safety, and/or disrupt their participation for the duration of the study
Outcome results
None listed