Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001375842
Ethics application status
Approved
Date submitted
24/08/2021
Date registered
11/10/2021
Date last updated
13/04/2024
Date data sharing statement initially provided
11/10/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
PsiConnect: Brain Connectivity and Context under Psilocybin
Scientific title
Investigating the impact of of Psilocybin and guided meditation on brain connectivity in healthy adults
Secondary ID [1] 305119 0
NIL
Universal Trial Number (UTN)
Trial acronym
PsiConnect
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neural mechanisms of psilocybin induced altered-states of consciousness 323343 0
Condition category
Condition code
Mental Health 320915 320915 0 0
Studies of normal psychology, cognitive function and behaviour

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
- 60 healthy participants will undergo fMRI (approx. 60 minutes) followed by and EEG (approx. 90 minutes hour) scans at two time points: [1] Approximately 1 week before oral capsule administration of 19mg psilocybin (baseline), [2] Day of psilocybin administration.

- Eligible participants are randomly stratified by age and sex then selected based on inexperience with use of classic psychedelics. All selected participants will be prepared with information about the effects of psilocybin and will undergo scanning procedures during baseline scanning.

- After Psilocybin ingestion, onset period lasting approximately 75 minutes will precede MRI/EEG scanning. Administering study doctor will ensure capsules are swallowed.


- Approx. 60 minutes MRI scans run by a radiologist will be accompanied by naturalistic visual stimuli
and meditation (open awareness) and music (ambient ethereal) to examine the influence of contextual factors on behavioural measures and brain connectivity. MRI is non-invasive imaging with no tracer/dye injection required.

- Approx. 90 minutes EEG scans run by research staff will include rest, guided meditation (open awareness) and music (participant selected and ambient ethereal). EEG electrodes will be placed on the scalp for recording electrical measurements.

- Training in meditation practice (mindfulness, focused attention, open awareness and self-compassion) will be delivered to half (30) participants in approximately 60 minutes session each week for 8 weeks. Participants will meditate daily for approximately 20 minutes with the option of guided meditation resources (Sam Harris meditation app). Adherence to meditation will be measured using FFMQ, MAQ, MEDI, EQ and SCS measures and weekly reflection questionnaires provided to participants.
Intervention code [1] 321517 0
Treatment: Drugs
Intervention code [2] 321521 0
Behaviour
Comparator / control treatment
Open label psilocybin (single dose 19 mg capsule) without guided 12-week meditation practice.
Control group
Active

Outcomes
Primary outcome [1] 328699 0
Change in brain effective (directed) connectivity measured, across all subjects and between groups using resting-state functional MRI
Timepoint [1] 328699 0
Baseline and day of dosing.
Primary outcome [2] 328700 0
Change in brain structural connectivity, across all subjects and between groups, measured using diffusion MRI.
Timepoint [2] 328700 0
Baseline and day of dosing.
Primary outcome [3] 329002 0
Change in brain functional connectivity, across all subjects and between groups, measured using resting state functional MRI.
Timepoint [3] 329002 0
Baseline and day of dosing.
Secondary outcome [1] 399993 0
[This is Primary Outcome 4]: Change in brain connectivity, across all subjects and between groups, measured using EEG.
Timepoint [1] 399993 0
Baseline and day of dosing.
Secondary outcome [2] 399994 0
Changes in composite depression, stress and anxiety; changes in depression scores; changes in anxiety scores , and changes in stress scores across all subjects and between groups, measured using the 21-item Depression Anxiety and Stress Scale (DASS-21) - self-rated.
Timepoint [2] 399994 0
Baseline, within 1 week post-, and 3-, 6- and 12-months post- dose.
Secondary outcome [3] 399996 0
Changes in composite self-reported dysphoria, well-being, panic, and depression, across all subjects and between groups, using the 99-item Expanded Version of the Inventory of Depression and Anxiety Symptoms (IDAS-II) scale.
Timepoint [3] 399996 0
Baseline, within 1 week post-, and 3-, 6- and 12-months post- dose.
Secondary outcome [4] 399997 0
Changes in quality of life, across all subjects and between groups, measured using the 16-item Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF).
Timepoint [4] 399997 0
Baseline, within 1 week post-, and 3-, 6- and 12-months post- dose.
Secondary outcome [5] 399998 0
Changes in quality of life, measured using the World Health Organisation Quality of Life Scale - Abbreviated version (WHO-Qol-Bref).
Timepoint [5] 399998 0
Baseline, within 1 week post-, and 3 months post- dose.
Secondary outcome [6] 399999 0
Participants’ big five personality traits measured using the NEO-FFI-3.
Timepoint [6] 399999 0
Baseline, within 1 week post-, and 3 months post- dose.
Secondary outcome [7] 400002 0
Changes in self-reported political perspectives, across all subjects and between groups, using the 5-item Political Perspective Questionnaire (PPQ-5).
Timepoint [7] 400002 0
Baseline, within 1 week post-, and 3-, 6- and 12-months post- dose.
Secondary outcome [8] 400003 0
Changes in self-reported nature-relatedness, across all subjects and between groups, using the 6-item Nature Relatedness Scale (NR-6).
Timepoint [8] 400003 0
Baseline, within 1 week post-, and 3-, 6- and 12-months post- dose.
Secondary outcome [9] 400004 0
Lasting subjective effects (e.g., sense of meaning, and other psychosocial factors of wellbeing and self-empowerment) across all subjects and between groups, measured with the Persisting Effects Questionnaire (PEQ).
Timepoint [9] 400004 0
Baseline, within 1 week post-, and 3-, 6- and 12-months post- dose.
Secondary outcome [10] 400005 0
Subjective ratings of the acute psychedelic experiences, across all subjects and between groups, assessed using the Mystical Experiences Questionnaire (MEQ).
Timepoint [10] 400005 0
Approximately 6 hours post dose administration.
Secondary outcome [11] 400006 0
Subjective ratings of the acute psychedelic experiences, across all subjects and between groups, assessed using the Aesthetic experiences scale (AES).
Timepoint [11] 400006 0
Baseline, within 1 week post-, and 3-, 6- and 12-months post- dose.
Secondary outcome [12] 400007 0
Subjective ratings of the acute psychedelic experiences, across all subjects and between groups, assessed using the Ego-Dissolution Inventory (EDI).
Timepoint [12] 400007 0
Approximately 6 hours post dose administration.
Secondary outcome [13] 400008 0
Subjective ratings of the acute psychedelic experiences, across all subjects and between groups, assessed using the 5-Dimension Altered States of Consciousness (5D-ASC).
Timepoint [13] 400008 0
Approximately 6 hours post dose administration.
Secondary outcome [14] 400009 0
Subjective ratings of the acute psychedelic experiences, across all subjects and between groups, assessed by research staff using 3 semi-structured interview questions exploring Resonance (Liking, Openness, Alignment).
Timepoint [14] 400009 0
5 minutes after presentation of music samples during EEG.
Secondary outcome [15] 400012 0
Changes in self-reported mindfulness and meditation, before and after psilocybin dosing, across all subjects and between groups, using the Five Facet Mindfulness Questionnaire (FFMQ). Composite outcome.
Timepoint [15] 400012 0
Weekly for 8 weeks prior to administration, and weekly for 4 weeks post administration.
Secondary outcome [16] 400013 0
Changes in self-reported mindfulness and meditation, before and after psilocybin dosing, using The Mindfulness Adherence Questionnaire (MAQ). Composite outcome
Timepoint [16] 400013 0
Weekly for 8 weeks prior to administration, and weekly for 4 weeks post administration.
Secondary outcome [17] 400014 0
Changes in self-reported mindfulness and meditation, before and after psilocybin dosing, using the Meditation Depth Questionnaire (MEDEQ). Composite outcome.
Timepoint [17] 400014 0
Weekly for 8 weeks prior to administration, and weekly for 4 weeks post administration.
Secondary outcome [18] 400015 0
Changes in self-reported mindfulness and meditation, before and after psilocybin dosing, using the Experiences Questionnaire (EQ). Composite outcome.
Timepoint [18] 400015 0
Weekly for 8 weeks prior to administration, and weekly for 4 weeks post administration.
Secondary outcome [19] 400016 0
Changes in self-reported mindfulness and meditation, before and after psilocybin dosing, using the Self-Compassion Scale (SCS). Composite outcome.
Timepoint [19] 400016 0
Weekly for 8 weeks prior to administration, and weekly for 4 weeks post administration.
Secondary outcome [20] 400017 0
Subjective ratings of emotional breakthrough, across all subjects and between groups, assessed using the Emotional Breakthrough Inventory (EBI).
Timepoint [20] 400017 0
Once within 1 week post-dose.
Secondary outcome [21] 400018 0
Self-reported mindfulness and meditation qualitative “Weekly reflections” describing mood and towards meditation, before and after psilocybin dosing. Composite measure to be analysed by thematic analysis.
Timepoint [21] 400018 0
Weekly for 8 weeks prior to administration and weekly for 4 weeks post administration.

Eligibility
Key inclusion criteria
Healthy adults aged between 18-55. No MRI contraindications. Willing to be abstinent from illicit or extra-medical drug and alcohol use for at least 2 days prior to psilocybin dosing. Able to swallow pills.
Proficient in English, such that their literacy and comprehension is sufficient for understanding the consent form and study questionnaires, as evaluated by study staff obtaining consent. (Funds available for this research would preclude access to translators to enable non-English speaker participation.) Limited previous exposure to psychedelics and meditation practices.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Current or previously diagnosed psychiatric disorder (as determined by the SCID). Current or past history within the last 5 years of meeting DSM-5 criteria for alcohol or drug dependence (excluding caffeine and nicotine), as determined by clinical interview and use of screening measures. Immediate family member with a diagnosed psychotic disorder (Schizophrenia spectrum, Disorder or Bipolar I or II Disorder). History of suicide attempts. No use of any hallucinogen or psychedelic (including psilocybin, MDMA, LSD, mescaline, DMT, and other similar hallucinogenic compounds) within the past 6 months. Taking a contraindicated medication (SSRIs, SNRIs, MAOIs) at the time of recruitment. Currently use of any of the following potent metabolic inducers or inhibitors: Inducers - Rifamycin (rifampin, rifabutin, rifapentine), anticonvulsants (carbamazepine, phenytoin, phenobarbital), nevirapine, efavirenz, paclitaxol, St John's Wort; Inhibitors - all HIV protease inhibitors, itraconazole, ketoconazole, erythromycin, clarithromycin, troleandomycin. Known conditions putting participants at risk for hypercalcaemia, Cushing's syndrome, hypoglycaemia, syndrome of inappropriate antidiuretic hormone secretion, or carcinoid syndrome. People with a medical requirement that they receive any of the following drugs with low therapeutic index within 12 hours after receiving psilocybin: ergot alkaloids, pimozide, midazolam, triazolam, lovastatin, simvastatin, fentanyl. A diagnosis of epilepsy or previous seizures. Hepatic dysfunction. Renal insufficiency (creatinine clearance < 40 mL/min using the Cockraft and Gault equation). Body weight < 48kg. Taking long-acting opioid pain medications (e.g. oxycodone sustained release, morphine sustained release -- which are usually taken at 12-hour intervals) unless last dose occurred at least 6 hours before psilocybin administration; such medication will not be taken again until at least 6 hours after psilocybin administration. Cardiovascular conditions: uncontrolled hypertension, (Systolic >140 and diastolic >90) angina, a clinically significant ECG abnormality (e.g. atrial fibrillation, arrhythmia, prolongation of QT/QTc interval), TIA in the last 6 months, stroke or cerebrovascular disease, peripheral or pulmonary vascular disease (no active claudication). Medically significant condition rendering unsuitability for the study (e.g., diabetes, epilepsy, severe cardiovascular disease, hepatic or renal failure etc). Treatment in another clinical trial involving an investigational product. Positive pregnancy test at screening or during the study. Are unable to give adequate informed consent. Allergy to gelatine or lactose.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample size is based upon the primary outcome measure of brain effective connectivity. Using brain effective connectivity as the primary outcome, (Preller and Razi et al., PNAS, 2019) showed changes in effective connectivity when placebo was compared with the treatment condition. Brain effective connectivity was inferred using spectral Dynamic Causal Modelling (Friston et al. 2014, Razi, et al. 2015). Using this Bayesian modelling procedure, the reported posterior expectation of effective connectivity, with N = 24, at a posterior probability threshold of > 0.95 (amounting to statistically `strong evidence’), was in the range of 0.1-0.4 Hz. Based upon these previously reported parameters, we aim to enrol 60 participants, 30 participants in each group (meditation and non-meditation) to ensure that we still have adequate power with an expected attrition rate of 20% in this trial.

Demographic and clinical data will be represented by descriptive statistics.

A parametric empirical Bayes analysis will be used at the group level to compare effective connectivity changes in meditation and non-mediation groups at both baseline and dosing day. Various secondary behavioural measures will be check for normality and if required transformed to Gaussian-like distributions using box-cox method. These will then be assessed using the appropriate classical statistics (tailed unpaired t-tests). Brain-behaviour relationships will be established using the parametric empirical Bayes method with a posterior probability threshold of > 0.95.

MRI data will be acquired on a Siemens Skyra 3 Tesla whole-body scanner, at the Monash Biomedical Imaging facility, using a 32-channel receive head coil. The acquired images will be analysed using SPM12 (developed at UCL, UK) neuroimaging software package. The preprocessing steps of the images will consist of slice time correction, realignment, spatial normalization to the standard EPI template of the Montreal Neurological Institute (MNI), and spatial smoothing using a Gaussian kernel of 6-mm full-width half-maximum.

EEG data will be acquired using BrainAmp MR Plus EEG System with 64 active electrodes also located the Monash Biomedical Imaging facility. The data will be pre-processed using SPM12. The 60Hz power line noise will be first removed. Afterwards, the data will be high-pass filtered using default settings, with a lower-cutoff of 1Hz. Then, a low-pass filter with high-cutoff of 45?Hz and default settings will be applied. Periods of data contaminated with blink artefacts will also be repaired using independent component analysis. Bad channels will be removed based on visual inspection. Finally, the data will be average-referenced.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/11/2021
Actual
10/01/2022
Date of last participant enrolment
Anticipated
30/11/2022
Actual
19/12/2022
Date of last data collection
Anticipated
23/06/2023
Actual
15/02/2024
Sample size
Target
60
Accrual to date
Final
60
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 35067 0
3168 - Clayton

Funding & Sponsors
Funding source category [1] 309507 0
University
Name [1] 309507 0
Turner Institute for Brain and Mental Health
Country [1] 309507 0
Australia
Funding source category [2] 309508 0
Charities/Societies/Foundations
Name [2] 309508 0
Canadian Institute for Advanced Research
Country [2] 309508 0
Canada
Primary sponsor type
University
Name
Monash University
Address
Wellington Road
Clayton
Victoria 3800
Australia
Country
Australia
Secondary sponsor category [1] 310488 0
None
Name [1] 310488 0
Address [1] 310488 0
Country [1] 310488 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309293 0
Monash University Human Research Ethics Committee (MUHREC)
Ethics committee address [1] 309293 0
Ethics committee country [1] 309293 0
Australia
Date submitted for ethics approval [1] 309293 0
08/03/2021
Approval date [1] 309293 0
20/04/2021
Ethics approval number [1] 309293 0
27181

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

Contacts
Principal investigator
Name 113658 0
A/Prof Adeel Razi
Address 113658 0
Monash Biomedical Imaging,
770 Blackburn Road,
Clayton, 3168, VIC
Country 113658 0
Australia
Phone 113658 0
+61399050109
Fax 113658 0
Email 113658 0
[email protected]
Contact person for public queries
Name 113659 0
Adeel Razi
Address 113659 0
Monash Biomedical Imaging,
770 Blackburn Road,
Clayton, 3168, VIC
Country 113659 0
Australia
Phone 113659 0
+61399050109
Fax 113659 0
Email 113659 0
[email protected]
Contact person for scientific queries
Name 113660 0
Adeel Razi
Address 113660 0
Monash Biomedical Imaging,
770 Blackburn Road,
Clayton, 3168, VIC
Country 113660 0
Australia
Phone 113660 0
+61399050109
Fax 113660 0
Email 113660 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?
Deidentified individual participant data will be available for all study outcomes (neuroimaging datasets and all secondary measures), however some demographic information may be withheld to protect participant confidentiality given the small sample size.
When will data be available (start and end dates)?
Start: Immediately following the publication of the main brain imaging findings.
End: 5 years after the completion of data collection
Available to whom?
Data will be made available on a case-by-case basis at the discretion of the principal investigator/primary sponsor.
Available for what types of analyses?
Any purpose.
How or where can data be obtained?
Access subject to approval by Principal Investigator (Adeel Razi; [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.