Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001315707
Ethics application status
Approved
Date submitted
20/06/2022
Date registered
11/10/2022
Date last updated
2/02/2023
Date data sharing statement initially provided
11/10/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
An open label study to evaluate the safety, tolerability, and subjective effects of two dimethyltryptamine (DMT) and harmala alkaloid containing formulations in healthy volunteers
Scientific title
AEOS: An open label study to evaluate the safety, tolerability, and subjective effects of two dimethyltryptamine (DMT) and harmala alkaloid containing formulations in healthy volunteers
Secondary ID [1] 307316 0
N/A
Universal Trial Number (UTN)
U1111-1279-1074
Trial acronym
AEOS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Depression 326606 0
Alcohol Use Disorder 326773 0
Trauma 326774 0
Condition category
Condition code
Mental Health 323849 323849 0 0
Studies of normal psychology, cognitive function and behaviour

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Initially, two orally administered DMT (1.0mg/kg) and harmala alkaloid formulations (4mg/kg) will be provided in separate single dose sessions to 8 healthy volunteers (with prior experience of these substances). After this data is collected, an interim assessment of the psychedelic effect and safety parameters will occur, with one of the formulations being chosen for the next dosage level. The amount given to the 8 partcipants will be increased to: DMT (1.4mg/kg) and harmala alkaloids (5.6mg/kg).

Participants will be given both formulations in a cross-over design (16 psychedelic sessions in total), with a 2-week washout between treatments. Initial treatment group assignment will be randomised. Post-monitoring will occur to assess the more chronic effects of the treatments.
Intervention code [1] 323761 0
Treatment: Drugs
Intervention code [2] 323762 0
Treatment: Other
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 331662 0
To assess the safety and tolerability based on AEs/SAEs- severity and frequency (as detailed in our purposed-designed AE case form). Further, vital sign data will be assessed, including blood pressure assessed by a sphygmomanometer, electrocardiogram via an ECG device, and pulse rate assessment via two fingers placed on the radial artery and the beats recorded according to a clock. Additionally, the Integration Difficulties Scale will be used to assess any negative effects of the treatment (1 week post-treatment).
Timepoint [1] 331662 0
Assessed acutely after treatment (i.e. 4-6 hours post-treatment) and chronically at follow-up assessments the day after treatment, and 1 week post-treatment. This assessment will be repeated at the next dosing level.
Primary outcome [2] 331663 0
To assess the formulations psychedelic effects on the Mystical Experiences Questionnaire (MEQ)
Timepoint [2] 331663 0
Assessed acutely after treatment (i.e. 4-6 hours post-treatment) and chronically at follow-up assessments the day after treatment, and 1 week post-treatment. This assessment will be repeated at the next dosing level.
Secondary outcome [1] 410664 0
To assess the formulations mental health effects via the Depression, Anxiety and Stress Scale (DASS21)
Timepoint [1] 410664 0
Depending on the scale, the mental health effects will be assessed either acutely after treatment (i.e. 4-6 hours post-treatment) and chronically at follow-up assessments on either the day after treatment, and 1 week post-treatment.
Secondary outcome [2] 410665 0
Assessing the psychedelic experience via the Short Index of Mystical Orientation (SIMO)
Timepoint [2] 410665 0
Assessed acutely after treatment (i.e. 4-6 hours post-treatment). This assessment will be repeated at the next dosing level.
Secondary outcome [3] 414528 0
5 Dimensions of Altered States of Consciousness (5D-ASC) scale
Timepoint [3] 414528 0
Assessed acutely after treatment (i.e. 4-6 hours post-treatment) and chronically at follow-up assessments the day after treatment, and 1 week post-treatment. This assessment will be repeated at the next dosing level.
Secondary outcome [4] 414529 0
Personal Insights Questionnaire will assess insights from the treatment experience
Timepoint [4] 414529 0
Assessed acutely after treatment (i.e. 4-6 hours post-treatment) and chronically at follow-up assessments the day after treatment, and 1 week post-treatment. This assessment will be repeated at the next dosing level.
Secondary outcome [5] 414530 0
Insomnia Severity Index (ISI) will assess any symptoms of insomnia
Timepoint [5] 414530 0
Assessed chronically at follow-up assessments the day after treatment, and 1 week post-treatment. This assessment will be repeated at the next dosing level.
Secondary outcome [6] 414531 0
Positive And Negative Affect Scale (PANAS) will assess acute affect
Timepoint [6] 414531 0
Assessed acutely after treatment (i.e. 4-6 hours post-treatment) and chronically at follow-up assessments the day after treatment, and 1 week post-treatment. This assessment will be repeated at the next dosing level.
Secondary outcome [7] 414532 0
Psychological distress is assessed via the Kessler-10 scale (K-10)
Timepoint [7] 414532 0
Assessed chronically at follow-up assessments the day after treatment, and 1 week post-treatment. This assessment will be repeated at the next dosing level.

Eligibility
Key inclusion criteria
1. 25 to 70-year-old men or women
2. Medically and psychiatrically healthy as adjudicated by the investigator based on physical exam and MINI (DSM-5) psychiatric interview.
3. Previous consumption of a DMT-harmaloid plant-based preparation
4. Weigh between 50kg and 90kg + a BMI of 18 to 32.
5. Voluntary consent to participate in the study (including follow-up visits) and to undergo the procedures requested.
6. Confirmation that a friend or family member will assist them personally with transport after the active drug session that evening.
7. Agree to alcohol abstinence 24 hours prior to the active treatment session and on the treatment day.
8. Willing to follow advice regarding sexual activity during the study.
Minimum age
25 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. History of psychosis: past or present diagnosis of bipolar disorder, schizophrenia, or schizoaffective disorder.
2. Family history of psychosis: past or present diagnosis of bipolar disorder type 1 in first degree relative, or schizophrenia, or schizoaffective disorder in first or second degree relative.
3. Current suicidality or history of suicide attempt.
4. Current psychiatric disorder diagnosis.
5. Daily/weekly high-risk alcohol use (as per NHMRC guidelines).
6. Use of any psychoactive medication (e.g., a selective serotonin reuptake inhibitor such as paroxetine or citalopram), haloperidol, any medication with MAO activity (such as isocarboxazid, phenelzine, selegiline or tranylcypromine, linezolid, and methylene blue), or any drug that has been indicated as a potential precipitative agent for serotonin syndrome within 28 days prior to study drug administration and through to the end of study.
7. Currently taking any other regular medication, including: Opiates, Anti-histamines, Anti-convulsants, Amphetamines, Kava, and St John’s wort.
8. Used a hallucinogen in the past month (a one-month wash-out is acceptable)
9. Smoking/using nicotine
10. Substance/alcohol use disorder
11. History of Hallucinogen Persisting Perception Disorder (HPPD).
12. Serious medical condition e.g., Cardiovascular, Metabolic, Neurological, Respiratory, Oncological, haematological disorder.
13. Serious ECG abnormality
14. Serious abnormal haematology or electrolyte, renal or liver test result (indicated by screening aspartate aminotransferase (AST) or alanine aminotransferase (ALT) 1.2X or total bilirubin 1.5 x upper limit of normal (ULN), which remains above these limits if retested) in the previous 12 months (as provided by their GP or SVHM).
15. Not agreeing to fasting from midnight prior to the Dose Day sessions until the afternoon of that treatment day.
16. Females who are pregnant, nursing, or trying to become pregnant (pregnancy test provided).
17. Participation in another clinical study involving investigational study treatment within 30 days or 5 half-lives, whichever is longer, prior to screening.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Crossover
Other design features
This study has random allocation between formulation groups, but no control
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
Continuous variables will be summarized descriptively providing, where applicable, the number of participants, mean, standard deviation, coefficient of variation, median, minimum (min) and maximum (max). Changes from baseline will be summarised descriptively providing, where applicable, the number of participants, mean, standard deviation, median, minimum (min) and maximum (max).

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
21/12/2022
Actual
Date of last participant enrolment
Anticipated
31/03/2023
Actual
Date of last data collection
Anticipated
1/05/2023
Actual
Sample size
Target
8
Accrual to date
0
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 22528 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment postcode(s) [1] 37767 0
3065 - Fitzroy

Funding & Sponsors
Funding source category [1] 311609 0
Commercial sector/Industry
Name [1] 311609 0
Psychae Therapeutics
Country [1] 311609 0
Australia
Primary sponsor type
Hospital
Name
St Vincent's Hospital, Melbourne
Address
St Vincent's Hospital Melbourne, VIC
P.O. Box 2900 Fitzroy 3065
Country
Australia
Secondary sponsor category [1] 313042 0
Charities/Societies/Foundations
Name [1] 313042 0
Psychae Institute
Address [1] 313042 0
Herbert Street, Northcote, Melbourne, VIC
3070
Country [1] 313042 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311051 0
St Vincent's Hospital, Melbourne
Ethics committee address [1] 311051 0
St Vincent's Hospital, Melbourne, VIC,
P.O. Box 2900 Fitzroy 3065
Ethics committee country [1] 311051 0
Australia
Date submitted for ethics approval [1] 311051 0
30/05/2022
Approval date [1] 311051 0
02/11/2022
Ethics approval number [1] 311051 0
118/22

Summary
Brief summary
The primary purpose of this study is to assess the safety and psychedelic effect of two orally administered DMT and harmala alkaloid formulations provided in separate sessions to healthy volunteers with prior use of these substances. This data will inform the decision to chose one of the formulations for use in a future phase 2 study involving participants with dual diagnosis and major depressive disorder. The potential dose escalation element will focus on determining the psychedelic properties and safety at a range of doses.
Trial website
Trial related presentations / publications
Public notes
N/A

Contacts
Principal investigator
Name 119822 0
A/Prof Yvonne Bonomo
Address 119822 0
St Vincent's Hospital Melbourne, VIC
P.O. Box 2900 Fitzroy 3065
Country 119822 0
Australia
Phone 119822 0
+613 9231 2627
Fax 119822 0
Email 119822 0
Yvonne.bonomo@svha.org.au
Contact person for public queries
Name 119823 0
Ms Amanda Norman
Address 119823 0
St Vincent's Hospital, VIC
P.O. Box 2900 Fitzroy 3065
Country 119823 0
Australia
Phone 119823 0
+613 9231 6940
Fax 119823 0
Email 119823 0
amanda.norman@svha.org.au
Contact person for scientific queries
Name 119824 0
A/Prof Yvonne Bonomo
Address 119824 0
St Vincent's Hospital Melbourne, VIC
P.O. Box 2900 Fitzroy 3065
Country 119824 0
Australia
Phone 119824 0
+613 9231 6940
Fax 119824 0
Email 119824 0
Yvonne.bonomo@svha.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
There are commercial sensitivities informing this decision


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.