Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000943549
Ethics application status
Approved
Date submitted
21/06/2024
Date registered
5/08/2024
Date last updated
8/09/2024
Date data sharing statement initially provided
5/08/2024
Type of registration
Retrospectively registered

Titles & IDs
Public title
Pharmacology of human decision making - Study of the effects of ketamine on healthy volunteers (18-55) making simple perceptual decisions
Scientific title
Pharmacology of human decision making (Phase 4 placebo-controlled ketamine hydrochloride study with healthy volunteers (18-55) targeting glutamatergic activity during perceptual decision making)
Secondary ID [1] 311693 0
Nil known
Universal Trial Number (UTN)
U1111-1305-2231
Trial acronym
PhD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cognitive function 333159 0
Condition category
Condition code
Neurological 329854 329854 0 0
Studies of the normal brain and nervous system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Ketamine injection - we will administer a single subcutaneous abdominal injection of ketamine hydrochloride, achieving a concentration of 0.7 mg/kg. As the intervention is a single injection, supervised by the study physician, no additional adherence monitoring is needed. There will be a one week washout period between active/placebo testing sessions.
Intervention code [1] 328157 0
Treatment: Drugs
Comparator / control treatment
In a placebo condition, participants will receive an abdominal injection, but this will be a saline solution of equivalent volume to the ketamine injection.
Control group
Placebo

Outcomes
Primary outcome [1] 337629 0
Accuracy on the decision task
Assessment method [1] 337629 0
Accuracy will be recorded by the computerised task as whether the participant correctly identifies the direction of coherent motion on each trial.
Timepoint [1] 337629 0
Accuracy will be recorded as participants complete the decision making task on each of the three testing sessions (baseline, active/placebo session 1, active/placebo session 2). The decision task, which will begin 10 minutes after administration, lasts 40 minutes.
Primary outcome [2] 337631 0
Reaction times on the decision task
Assessment method [2] 337631 0
Reaction times will be recorded by the computerised task as the interval between evidence onset (i.e. coherent motion) and the participant response on each trial.
Timepoint [2] 337631 0
Reaction times will be recorded as participants complete the decision making task on each of the three testing sessions (baseline, active/placebo session 1, active/placebo session 2). The decision task, which will begin 10 minutes after administration, lasts 40 minutes.
Primary outcome [3] 338773 0
Decision process dynamics
Assessment method [3] 338773 0
Electroencephalograhic (EEG) signals linked to key stages of the decision process will be analysed to offer insight into the effects of glutamate challenge on decision formation. These signals include well-established neurophysiological signatures of evidence accumulation (centroparietal positivity), attention/task engagement (alpha oscillatory activity), decision urgency (contingent negative variation), and response preparation (desynchronisation of beta oscillatory activity). This is considered a composite outcome because each signal's dynamics must be considered in the context of the other signals to draw conclusions about the decision process.
Timepoint [3] 338773 0
EEG will be recorded as participants complete the decision making task during each of the three testing sessions (baseline, active/placebo session 1, active/placebo session 2). The decision task, which will begin 10 minutes after administration, lasts 40 minutes.
Secondary outcome [1] 432583 0
Depression
Assessment method [1] 432583 0
Depression will be assessed with a number of online self-report questionnaires delivered through Qualtrics. The questionnaires will be analysed as a composite outcome to develop an profile of the participants experience of depression symptoms over the course of participation. There will be three types of questionnaire: 1) Baseline questionnaire - participants will complete a baseline questionnaire to establish baseline levels of depression. This will allow us to identify if any changes in psychological wellbeing detected over the course of the experiment were more/less pronounced based on these baseline scores. The questionnaire broadly target how the participant feels in general, rather than being specific to a narrow window of time. These measures include: 1a) The Beck Depression Inventory 1b) The Perceived Stress Scale 2) Pre-testing questionnaire - participants will complete a questionnaire before starting the decision task on each of the testing days. These questionnaires will monitor changes in their mood and wellbeing on a session-by-session basis, allowing us to isolate any effect of ketamine. These measures ask the participant to describe how they felt in the interval since the last testing session. These measures include: 2a) The Depression Anxiety Stress Scale 21 2b) The Patient Health Questionnaire 9 2c) The Clinical Outcomes in Routine Evaluation 10 3) Post-testing questionnaire - after participants have completed the task, they will complete a questionnaire, which repeats some of the pre-testing measures and includes some additional measures designed to assess the effect of ketamine on the participant. They will be used to assess the acute effects of ketamine. They include: 3a) The Positive and Negative Affect Schedule
Timepoint [1] 432583 0
The baseline questionnaire will be completed at any time in advance of the baseline testing session. The pre- and post-testing questionnaires will be completed upon arrival (approx. 1 hour before starting the task) and immediately after completing the task on each of the testing days (baseline, active/placebo session 1, and active/placebo session 2). Participants will complete a final pre-testing questionnaire 1 week after participation in the final testing session.
Secondary outcome [2] 437396 0
Anxiety
Assessment method [2] 437396 0
Anxiety will be assessed with a number of online self-report questionnaires delivered through Qualtrics. The questionnaires will be analysed as a composite outcome to develop an profile of the participants experience of anxiety symptoms over the course of participation. There will be three types of questionnaire: 1) Baseline questionnaire - participants will complete a baseline questionnaire to establish baseline levels of anxiety. This will allow us to identify if any changes in psychological wellbeing detected over the course of the experiment were more/less pronounced based on these baseline scores. The questionnaire broadly target how the participant feels in general, rather than being specific to a narrow window of time. These measures include: 1a) The Brief Fear of Negative Evaluation Scale 1b) The Social Avoidance and Distress Scale 1c) The Perceived Stress Scale 2) Pre-testing questionnaire - participants will complete a questionnaire before starting the decision task on each of the testing days. These questionnaires will monitor changes in their mood and wellbeing on a session-by-session basis, allowing us to isolate any effect of ketamine. These measures ask the participant to describe how they felt in the interval since the last testing session. These measures include: 2a) The State-Trait Anxiety Inventory 2b) The Generalised Anxiety Disorder 7 2c) APA Severity Measure for Social Anxiety Disorder 2d) The Depression Anxiety Stress Scale 21 2e) The Clinical Outcomes in Routine Evaluation 10 3) Post-testing questionnaire - after participants have completed the task, they will complete a questionnaire, which repeats some of the pre-testing measures and includes some additional measures designed to assess the effect of ketamine on the participant. They will be used to assess the acute effects of ketamine. They include: 3a) The State-Trait Anxiety Inventory 3b) The Positive and Negative Affect Schedule
Timepoint [2] 437396 0
The baseline questionnaire will be completed at any time in advance of the baseline testing session. The pre- and post-testing questionnaires will be completed upon arrival (approx. 1 hour before starting the task) and immediately after completing the task on each of the testing days (baseline, active/placebo session 1, and active/placebo session 2). Participants will complete a final pre-testing questionnaire 1 week after participation in the final testing session.
Secondary outcome [3] 437399 0
Dissociation
Assessment method [3] 437399 0
Dissociative symptoms will be assessed with a number of online self-report questionnaires delivered through Qualtrics. The questionnaires will be analysed as a composite outcome to develop a profile of the participants experience of dissociative symptoms over the course of participation. There will be three types of questionnaire: 1) Baseline questionnaire - participants will complete a baseline questionnaire to establish baseline levels of dissociative experiences. This will allow us to identify if any changes in psychological wellbeing detected over the course of the experiment were more/less pronounced based on these baseline scores. The questionnaire broadly targets how the participant feels in general, rather than being specific to a narrow window of time. These measures include: 1a) The Dissociative Experiences Scale II (dissociative symptoms) 2) Pre-testing questionnaire - participants will complete a questionnaire before starting the decision task on each of the testing days. These questionnaires will monitor changes in their mood and wellbeing on a session-by-session basis, allowing us to isolate any effect of ketamine. These measures ask the participant to describe how they felt in the interval since the last testing session. These measures include: 2a) The Cambridge Depersonalisation Scale - State Version 2b) The Clinician Administered Dissociative Symptoms Scale 3) Post-testing questionnaire - after participants have completed the task, they will complete a questionnaire, which repeats some of the pre-testing measures and includes some additional measures designed to assess the effect of ketamine on the participant. They will be used to assess the acute effects of ketamine. They include: 2a) The Cambridge Depersonalisation Scale - State Version 2b) The Clinician Administered Dissociative Symptoms Scale
Timepoint [3] 437399 0
The baseline questionnaire will be completed at any time in advance of the baseline testing session. The pre- and post-testing questionnaires will be completed upon arrival (approx. 1 hour before starting the task) and immediately after completing the task on each of the testing days (baseline, active/placebo session 1, and active/placebo session 2). Participants will complete a final pre-testing questionnaire 1 week after participation in the final testing session.
Secondary outcome [4] 437401 0
Obsessive-compulsive symptoms
Assessment method [4] 437401 0
Obsessive-compulsive symptoms will be assessed with a number of online self-report questionnaires delivered through Qualtrics. The questionnaires will be analysed as a composite outcome to develop an profile of the participants experience of obsessive-compulsive symptoms over the course of participation. There will be two types of questionnaire: 1) Baseline questionnaire - participants will complete a baseline questionnaire to establish baseline levels of obsessive-compulsive symptoms. This will allow us to identify if any changes in psychological wellbeing detected over the course of the experiment were more/less pronounced based on these baseline scores. The questionnaire broadly target how the participant feels in general, rather than being specific to a narrow window of time. These measures include: 1a) The Vancouver Obsessional Compulsive Inventory 2) Pre-testing questionnaire - participants will complete a questionnaire before starting the decision task on each of the testing days. These questionnaires will monitor changes in their mood and wellbeing on a session-by-session basis, allowing us to isolate any effect of ketamine. These measures ask the participant to describe how they felt in the interval since the last testing session. These measures include: 2a) The Obsessive Compulsive Inventory Revised (OCD symptoms)
Timepoint [4] 437401 0
The baseline questionnaire will be completed at any time in advance of the baseline testing session. The pre-testing questionnaires will be completed upon arrival (approx. 1 hour before starting the task) on each of the testing days (baseline, active/placebo session 1, and active/placebo session 2). Participants will complete a final pre-testing questionnaire 1 week after participation in the final testing session.
Secondary outcome [5] 437402 0
Life satisfaction/general wellbeing
Assessment method [5] 437402 0
Life satisfaction/general wellbeing will be assessed with online self-report questionnaires delivered through Qualtrics. The questionnaires will be analysed as a composite outcome to develop an profile of the participant's life satisfaction/general wellbeing over the course of participation. 1) Post-testing questionnaire - after participants have completed the task, they will complete a questionnaire, which repeats some of the pre-testing measures and includes some additional measures designed to assess the effect of ketamine on the participant. They will be used to assess the acute effects of ketamine. These measure include: 1a) The Subjective Happiness Scale 1b) The Personal Wellbeing Index Adult 1c) The Rosenberg Self-Esteem Scale 1d) The Compassion Motivation and Action Scales - Self
Timepoint [5] 437402 0
The post-testing questionnaires will be completed immediately after completing the task on each of the testing days (baseline, active/placebo session 1, and active/placebo session 2).
Secondary outcome [6] 437403 0
Fatigue
Assessment method [6] 437403 0
fatigue will be assessed with online self-report questionnaires delivered through Qualtrics. 1) Pre-testing questionnaire - participants will complete a questionnaire before starting the decision task on each of the testing days. These measures include: 1a) The Karolinska Sleepiness Scale 2) Post-testing questionnaire - after participants have completed the task, they will complete a questionnaire, which repeats some of the pre-testing measures and includes some additional measures designed to assess the effect of ketamine on the participant. They will be used to assess the acute effects of ketamine. They include: 2a) The Karolinska Sleepiness Scale
Timepoint [6] 437403 0
The pre- and post-testing questionnaires will be completed upon arrival (approx. 1 hour before starting the task) and immediately after completing the task on each of the testing days (baseline, active/placebo session 1, and active/placebo session 2).

Eligibility
Key inclusion criteria
Aged 18-55

Right-handed

Normal or corrected-to-normal vision (glasses and contact lenses are ok)

No knowledge of any reason why they should not be given ketamine
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Any cardiac conditions or history of high blood pressure

Assessed as having any contraindication to ketamine by our study physician

Assessed as suffering from a psychiatric disorder (according to DSM-V criteria) by our study physician

History of epilepsy

Females not on hormonal contraception

Pregnant or currently breastfeeding

Personal history of psychiatric or neurological illness

Family history of psychotic illness

Report any previous usage of antipsychotic or stimulant medication

History of significant* drug use
*'Significant' defined as (i) use of any illicit substances within the last 6 months; (ii) >5 lifetime intake of any illicit drug, except cannabis; (iii) more than monthly cannabis intake in the last 6 months

Current smoker or have smoked more than 5 cigarettes per week in their lifetime

Dependent on alcohol and consume more than 24 units/week

Currently taking any of the following substances: St. John's Wort, rifampin, grapefruit juice, clarithromycin

Study design
Purpose of the study
Educational / counselling / training
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation to treatment schedules will be handled by a third party using a computerised randomisation script. That person will not involved in any stage of recruitment. The randomised schedule will be sent to the clinical pharmacy that prepare the doses, but will not seen by any member of the research team. The research team will remain blinded until the final participant has completed their last testing session.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A randomisation code will be generated by a third-party using computer software and supplied to the clinical pharmacy supplying the doses. The code randomly assigns participants to one of two schedules (placebo -> active or active -> placebo) using their participant ID code. The code also ensures there is an even ratio of participants assigned to each schedule. The research team will only receive the randomisation code for analysis after data collection is complete.
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
Crossover
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
14/06/2024
Date of last participant enrolment
Anticipated
17/10/2024
Actual
Date of last data collection
Anticipated
31/10/2024
Actual
Sample size
Target
35
Accrual to date
24
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 316022 0
University
Name [1] 316022 0
Monash University
Country [1] 316022 0
Australia
Primary sponsor type
University
Name
Monash University
Country
Australia
Secondary sponsor category [1] 318174 0
None
Name [1] 318174 0
Country [1] 318174 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314845 0
Monash University Human Research Ethics Committee
Ethics committee address [1] 314845 0
Ethics committee country [1] 314845 0
Australia
Date submitted for ethics approval [1] 314845 0
22/02/2024
Approval date [1] 314845 0
28/02/2024
Ethics approval number [1] 314845 0
37698

Summary
Brief summary
Trial website
Public notes

Contacts
Principal investigator
Name 132906 0
Prof Mark Bellgrove
Address 132906 0
School of Psychological Sciences, Monash University, Room 540, 18 Innovation Walk, Clayton Campus, Clayton, VIC 3800
Country 132906 0
Australia
Phone 132906 0
+61 3 9902 4200
Email 132906 0
mark.bellgrove@monash.edu
Contact person for public queries
Name 132907 0
Mark Bellgrove
Address 132907 0
School of Psychological Sciences, Monash University, Room 540, 18 Innovation Walk, Clayton Campus, Clayton, VIC 3800
Country 132907 0
Australia
Phone 132907 0
+61 3 9902 4200
Email 132907 0
BellgroveTeam@monash.edu
Contact person for scientific queries
Name 132908 0
Mark Bellgrove
Address 132908 0
School of Psychological Sciences, Monash University, Room 540, 18 Innovation Walk, Clayton Campus, Clayton, VIC 3800
Country 132908 0
Australia
Phone 132908 0
+61 3 9902 4200
Email 132908 0
mark.bellgrove@monash.edu

Data sharing statement
Will the study consider sharing individual participant data?
Yes
Will there be any conditions when requesting access to individual participant data?
Persons/groups eligible to request access:
• Open science repositories are accessible to anyone

Conditions for requesting access:
• -

What individual participant data might be shared?
• De-identified behavioural and electrophysiological data

What types of analyses could be done with individual participant data?
• Access is not contingent on an analysis plan

When can requests for individual participant data be made (start and end dates)?
From:
The data will be uploaded to an open science repository as part of the publication process

To:
-

Where can requests to access individual participant data be made, or data be obtained directly?
• The data will be accessible via the Open Science Framework (OSF; https://osf.io/).

Are there extra considerations when requesting access to individual participant data?
No


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.