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Trial registered on ANZCTR


Registration number
ACTRN12623001064695
Ethics application status
Approved
Date submitted
30/08/2023
Date registered
4/10/2023
Date last updated
16/06/2024
Date data sharing statement initially provided
4/10/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Low dose psilocybin as a treatment for moderate depression
Scientific title
A Double-Blind Randomised Controlled Trial of the Efficacy of Microdosing with Psilocybin to treat Moderate Depression
Secondary ID [1] 309223 0
MICRODEP01
Universal Trial Number (UTN)
Trial acronym
MICRODEP01
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Major Depressive Disorder of moderate severity 329373 0
Condition category
Condition code
Mental Health 326316 326316 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 325665 0
Treatment: Drugs
Comparator / control treatment
Participants in the control group will be administered caffeine in identical capsules (60 mg).
Control group
Placebo

Outcomes
Primary outcome [1] 334176 0
Change in the Hamilton Rating Scale for Depression (GRID-HAMD) from baseline
Timepoint [1] 334176 0
Baseline and 6 weeks from baseline
Secondary outcome [1] 423967 0
1. Change in GRID-HAMD from baseline to week 10
Timepoint [1] 423967 0
Baseline and 1-month followup visit (week 10)
Secondary outcome [2] 423968 0
2. Rates of clinical response (50% reduction on GRID-HAMD from baseline score) at week 6 (study endpoint) and week 10 (1M FollowUp)
Timepoint [2] 423968 0
Study endpoint (week 6 post-baseline) & 1-month followup visit (week 10 post-baseline)
Secondary outcome [3] 423969 0
3. Rates of remission (score <8 on GRID-HAMD) at week 6 (primary endpoint) and week 10 (1M FollowUp)
Timepoint [3] 423969 0
Study endpoint (week 6 post-baseline) & 1-month followup visit (week 10 post-baseline)
Secondary outcome [4] 423970 0
4. Proportion of participants with Severe Adverse Events or Adverse Events (e.g., headache, nausea, dizziness) associated with participation in the trial from week 1 through to week 6. Adverse events will be assessed using a study specific questionnaire.
Timepoint [4] 423970 0
At conclusion of study.
Secondary outcome [5] 423971 0
5. Proportion of participants with suicidality (Columbia Suicide Severity Rating Scale [CSSRS] - Brief Form scores >1) during the study
Timepoint [5] 423971 0
At conclusion of study
Secondary outcome [6] 423972 0
6. Proportion of participants who down-titrate dose (determined by audit of study records)
Timepoint [6] 423972 0
At conclusion of study
Secondary outcome [7] 423973 0
7. Proportion of participants who remain in study until study week 6 (study endpoint) and week 10 (1M FollowUp). This will be determined by audit of study records.
Timepoint [7] 423973 0
At conclusion of study
Secondary outcome [8] 423974 0
8. Change in Sheehan Disability Scale (SDS) from baseline to week 6 and week 10
Timepoint [8] 423974 0
Baseline and study endpoint (week 6 post-baseline) & 1-month followup visit (week 10 post-baseline)
Secondary outcome [9] 423975 0
9. Change in driving simulator performance from baseline to week 1 and week 5
Timepoint [9] 423975 0
Baseline, visit 1B (week 1 post-baseline) and 5B (week 5 post-baseline)
Secondary outcome [10] 423976 0
10. Change in cognitive function, assessed using the trailmaking test, from baseline to visits 1B, 2B, 3B, 4B, and 5B
Timepoint [10] 423976 0
Baseline, visit 1B (week 1 post-baseline), 2B (week 2 post-baseline), 3B (week 3 post-baseline), 4B (week 4 post-baseline), and 5B (week 5 post-baseline)
Secondary outcome [11] 423980 0
11. Change in wellbeing, assessed with the EQ-5D, from baseline to week 6 and week 10
Timepoint [11] 423980 0
Baseline and study endpoint (week 6 post-baseline) & 1-month followup visit (week 10 post-baseline)
Secondary outcome [12] 423981 0
12. Change in anxiety, assessed with the Depression, Anxiety, Stress Scale from baseline to week 6 and week 10
Timepoint [12] 423981 0
Baseline and study endpoint (week 6 post-baseline) & 1-month followup visit (week 10 post-baseline)
Secondary outcome [13] 423982 0
13. Change in alcohol misuse, assessed with the Alcohol, Smoking and Substance Involvement Test, from baseline to week 6 and week 10
Timepoint [13] 423982 0
Baseline and study endpoint (week 6 post-baseline) & 1-month followup visit (week 10 post-baseline)
Secondary outcome [14] 423983 0
14. Change in drug misuse, assessed with the Alcohol, Smoking and Substance Involvement Test, from baseline to week 6 and week 10
Timepoint [14] 423983 0
Baseline and study endpoint (week 6 post-baseline) & 1-month followup visit (week 10 post-baseline)
Secondary outcome [15] 423984 0
15. Change in tobacco misuse, assessed with the Alcohol, Smoking and Substance Involvement Test, from baseline to week 6 and week 10
Timepoint [15] 423984 0
Baseline and study endpoint (week 6 post-baseline) & 1-month followup visit (week 10 post-baseline)
Secondary outcome [16] 426694 0
16. Ratings of the Acceptability of Intervention Measure (AIM) at week 6
Timepoint [16] 426694 0
Study endpoint (week 6 post-baseline)
Secondary outcome [17] 426695 0
17. Ratings of the Intervention Appropriateness Measure (IAM) at week 6
Timepoint [17] 426695 0
Study endpoint (week 6 post-baseline)
Secondary outcome [18] 426696 0
18. Ratings of the Feasibility of Intervention Measure (FIM) at week 6
Timepoint [18] 426696 0
Study endpoint (week 6 post-baseline)
Secondary outcome [19] 426697 0
19. Change in blood-based biomarker battery (includine tryptophan metabolites, multiplex cytokine array, and enzyme-linked immunosorbent array) from baseline to week 1 and week 3 (acute biomarkers)
Timepoint [19] 426697 0
Baseline, visit 1A (week 1 post-baseline), and 3B (week 3 post-baseline)
Secondary outcome [20] 426698 0
20. Change in blood-based biomarker battery (includine tryptophan metabolites, multiplex cytokine array, and enzyme-linked immunosorbent array) from baseline to week 6, week 7 and week 10 (sustained biomarkers)
Timepoint [20] 426698 0
Baseline, study endpoint (week 6 post-baseline), 1-week followup (week 7 post-baseline), and 1-month followup (week 10 post-baseline)
Secondary outcome [21] 426699 0
21. Changes in visual long term potentitation, measured with magnetoencephlatography (MEG) from baseline to first dosing day.
Timepoint [21] 426699 0
Baseline and visit 1A (week 1 post-baseline)
Secondary outcome [22] 426700 0
22. Changes in resting state, measured with MEG from baseline to first dosing day.
Timepoint [22] 426700 0
Baseline and visit 1A (week 1 post-baseline)
Secondary outcome [23] 426701 0
23. Changes in auditory oddball performance, measured with MEG from baseline to first dosing day
Timepoint [23] 426701 0
Baseline and visit 1A (week 1 post-baseline)

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation will be performed automatically by computer after eligibility is determined.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Stratified Randomization using REDCap.
The strata being used on this trial is age (greater or lower than 35) & sex assigned at birth (male, female, intersex)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Sample size and Statistical Considerations
We aim to recruit 266 participants for this study. This will allow us to detect an effect size of .4 for the primary outcome variable GRID-HAMD, with statistical power 90% and statistical significance level .05 (two-tailed). We anticipate a drop-out rate of 10%. Although the analytic approach adopted for this study uses all available data for all enrolled patients, due to the possibility of fewer EOT measurements than expected our actual recruitment target is 293.

Analysis Populations
Modified Intention-to-Treat (mITT) – is defined as all randomised participants who received at one dose of the study treatment.

Analysis of the Primary Outcome
The primary statistical analysis involves the change in the primary outcome variable (GRID-HAMD Depression scores) between the baseline visit and the end of treatment (EOT) visit (Week 6B). A contrast of study groups will be made via linear mixed models estimated via maximum likelihood. The model will include the main effects of Visit and Study group and the interaction between them. The interaction term will be statistically tested as it is a direct estimate of the difference in change with treatment between the active and placebo groups. This approach is known to be unbiased in the presence of missing values. Should the assumption of normality not be met, formal statistical inference will employ the nonparametric bootstrap.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
9/10/2023
Actual
9/02/2024
Date of last participant enrolment
Anticipated
30/10/2027
Actual
Date of last data collection
Anticipated
30/01/2028
Actual
Sample size
Target
293
Accrual to date
2
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment postcode(s) [1] 40762 0
2109 - Macquarie University

Funding & Sponsors
Funding source category [1] 313412 0
Commercial sector/Industry
Name [1] 313412 0
Woke Pharmaceuticals
Country [1] 313412 0
Australia
Primary sponsor type
University
Name
Macquarie University
Address
Clinical Trials UnitLevel 3, 75 Talavera RoadMacquarie University 2109 NSW
Country
Australia
Secondary sponsor category [1] 316186 0
None
Name [1] 316186 0
Address [1] 316186 0
Country [1] 316186 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312628 0
Macquarie University HREC
Ethics committee address [1] 312628 0
Ethics committee country [1] 312628 0
Australia
Date submitted for ethics approval [1] 312628 0
30/01/2023
Approval date [1] 312628 0
23/02/2023
Ethics approval number [1] 312628 0
520231245146817

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 125338 0
Dr Vince Polito
Address 125338 0
Level 3, Room 3.81316 University AveMacquarie University, NSW 2109
Country 125338 0
Australia
Phone 125338 0
+61 2 98502966
Fax 125338 0
Email 125338 0
[email protected]
Contact person for public queries
Name 125339 0
Dr Vince Polito
Address 125339 0
Clinical Trials UnitLevel 3, 75 Talavera RoadMacquarie University, NSW 2109
Country 125339 0
Australia
Phone 125339 0
+61 72301367
Fax 125339 0
Email 125339 0
[email protected]
Contact person for scientific queries
Name 125340 0
Vince Polito
Address 125340 0
Level 3, Room 3.81316 University AveMacquarie University, NSW 2109
Country 125340 0
Australia
Phone 125340 0
+61 2 9850 2966
Fax 125340 0
Email 125340 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified data related to registered study measures will be shared
When will data be available (start and end dates)?
Start: immediately following the publication of the long-term follow-up results
End: indefinitely
Available to whom?
Anyone who wishes to access it
Available for what types of analyses?
Any purpose
How or where can data be obtained?
Data will be shared in the Macquarie University Research Data Repository.
Data requests can also be sent to [email protected]


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.