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Trial registered on ANZCTR


Registration number
ACTRN12616001485426
Ethics application status
Approved
Date submitted
29/09/2016
Date registered
25/10/2016
Date last updated
22/05/2017
Type of registration
Retrospectively registered

Titles & IDs
Public title
Ketamine, cognition and driving performance
Scientific title
The Effect of Three Stepwise Doses of Intravenously Administered Ketamine Infusions on Cognitive Functioning and Simulated Driving Performance.
Secondary ID [1] 290240 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Drugged driving 300433 0
Condition category
Condition code
Injuries and Accidents 300299 300299 0 0
Other injuries and accidents
Mental Health 300346 300346 0 0
Studies of normal psychology, cognitive function and behaviour

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will receive all three of the following treatments during the experimental period:
IV Ketamine infusion (low dose, Step 1), comprising 8mg/hour IV infusion
Plus initial (one-off) 30mg bolus of ketamine solution. The one-off bolus is administered at the beginning of the infusion.
IV Ketamine infusion (medium dose, Step 2), comprising 12mg/hour IV infusion
IV Ketamine infusion (high dose, Step 3), comprising 20mg/hour IV infusion.
All infusions are timed for one hour. A five minute gap is timed between infusion steps. Adherence is monitored by electronically-timed infusion.
Intervention code [1] 296020 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 299773 0
Associations between the treatment (ketamine infusion low, medium and high dose) and driving performance (day and night-time highway and city driving scenarios).
Timepoint [1] 299773 0
After administration of treatment (low medium and high ketamine treatment). Specifically, this will occur at baseline, 30 mins post each treatment step (each following low, medium and high treatment infusion), and 2 hours post-final treatment. This will be assessed using the Forum 8 driving simulator. Weaving of the car, expressed as standard deviation of the lateral position (SDLP), standard deviation of speed (SDS, km/h) and lapses will be assessed.
Primary outcome [2] 299774 0
Associations between the treatment (ketamine infusion low, medium and high dose) and neurocognitive ability (CANTAB computerised battery).

Timepoint [2] 299774 0
After administration of treatment (low medium and high ketamine treatment). Specifically, this will occur at baseline, 30 mins post treatment (each following low, medium and high treatment), and 2 hours post-final treatment. This will be assessed using the CANTAB cognitive battery; where reaction time, spatial working memory and working memory will be assessed.
Secondary outcome [1] 328080 0
Concentration of plasma levels of ketamine across time. This will be assessed by taking 5ml blood sample.
Timepoint [1] 328080 0
After administration of treatment (low medium and high ketamine treatment). Specifically, this will occur at 30 mins post treatment (each following low, medium and high treatment), and 2 hours post-final treatment.
Secondary outcome [2] 328081 0
Association between treatment plasma concentrations across time and cognitive performance. This will be assessed by blood samples and by the CANTAB computerised battery scores for reaction time, spatial working memory and working memory.
Timepoint [2] 328081 0
After administration of treatment (low medium and high ketamine treatment). Specifically, this will occur at 30 mins post treatment (each following low, medium and high treatment), and 2 hours post-final treatment
Secondary outcome [3] 328082 0
Level of alertness over time as a function of treatment step. This will be assessed using subjective alertness questions which comprise part of the CANTAB battery.
Timepoint [3] 328082 0
After administration of treatment (low medium and high ketamine treatment). Specifically, this will occur at baseline, 30 mins post treatment (each following low, medium and high treatment), and 2 hours post-final treatment
Secondary outcome [4] 328083 0
Association between treatment plasma concentrations across time and driving simulator performance compared to baseline. This will be assessed using the Forum 8 driving simulator. Weaving of the car, expressed as standard deviation of the lateral position (SDLP), standard deviation of speed (SDS, km/h) and lapses will be assessed.
Timepoint [4] 328083 0
After administration of treatment (low medium and high ketamine treatment). Specifically, this will occur at baseline, 30 mins post treatment (each following low, medium and high treatment), and 2 hours post-final treatment
Secondary outcome [5] 328085 0
Relatedness to performance outcomes on the cognitive and driving simulator tasks. This will be assessed by evaluating he predictive ability of performance on the CANTAB cognitive battery to performance on the driving simulator task.
Timepoint [5] 328085 0
After administration of treatment (low medium and high ketamine treatment). Specifically, this will occur at 30 mins post treatment (each following low, medium and high treatment), and 2 hours post-final treatment

Eligibility
Key inclusion criteria
Aged between 21 and 45 years.
Hold a full drivers licence (no ā€˜Pā€™ plates).
No known allergic reaction to ketamine or other related opioids.
Have no history of past substance abuse or current abuse of illicit drugs.
Have no pre-existing physical or neurological conditions, no previous or current history of severe psychiatric, cardiac, endocrine, gastrointestinal, or bleeding disorders.
Not currently pregnant or lactating
Minimum age
21 Years
Maximum age
45 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Inability to speak or read English.
Taking any form of medication within 5 days of admission (except for prophylactic antibiotics, contraceptive pill or other routine medications to treat benign conditions, such as antibiotics to treat acne) and agree not to take any medication throughout the study.
Unable to participate in scheduled visit, treatment plan, tests and other trial procedures according to the protocol.
Current participation in any other trials involving investigational or marketed products within 30 days prior to the screening visit.

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)
Non-randomised trial
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
This study will employ a within subjects design, and will be open label.
Phase
Phase 1
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Demographic data will be presented with summary statistics (number of participants, mean, standard deviation, median and range). The number and percentage of subjects will be presented for categorical variables.
All statistical tests will be performed two tailed at the 5% significance level and performed using IBM SPSS statistical package. Z scores for the distribution will be calculated for each variable and displayed in histogram form. Out of range values will be recoded as missing values.
Results for the driving simulator will be assessed using a within subjects one-way analysis of covariance (ANCOVA), with treatment step (Step 1, 2 or 3) as the within-subject variable and baseline score as the covariate.
Results for the CANTAB cognitive battery will also be compared using a within subjects one-way analysis of covariance (ANCOVA), with treatment step (Step 1, 2 or 3) as the within-subject variable, and baseline score as the covariate.
Correlations between CANTAB VAS scores and performance outcomes on CANTAB tasks and the driving simulator across time points as function of treatment will be conducted using Pearson product moment coefficient r.
The relationship between ketamine plasma concentrations and VAS effects will be analysed by linear regression.
Results for the Drugwipe 6S will be assessed as function of treatment and will be presented as a binary outcome (detection yes/no). A binary logistic regression model will be used, with detection status (present/absent) as the outcome, and treatment step (Step 1, 2 or 3) used as the categorical predictor variable. Baseline data and demographic information will be entered sequentially to assess for possible effect-modification.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 294769 0
Hospital
Name [1] 294769 0
Monash Medical Centre
Address [1] 294769 0
Monash Medical Centre
246 Clayton Road
Clayton Victoria 3168
Country [1] 294769 0
Australia
Primary sponsor type
Hospital
Name
Monash Medical Centre
Address
Monash Medical Centre
246 Clayton Road
Clayton Victoria 3168
Country
Australia
Secondary sponsor category [1] 293614 0
None
Name [1] 293614 0
Address [1] 293614 0
Country [1] 293614 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296050 0
Monash Health Human Research Ethics Committee
Ethics committee address [1] 296050 0
Ethics committee country [1] 296050 0
Australia
Date submitted for ethics approval [1] 296050 0
24/06/2016
Approval date [1] 296050 0
11/08/2016
Ethics approval number [1] 296050 0
HREC/16/MonH/240

Summary
Brief summary
The clinical utility of ketamine as demonstrated efficacy as a novel antidepressant and anti-anxiolytic, as well as a low-risk, effective tool to manage chronic pain among treatment resistant patients. Perhaps paradoxically, however, the associated cognitive, behavioural and attention impairments pose significant implications for driving ability and road safety. Despite this, no studies are currently available which explicitly assess the effect of sub-anaesthetic doses of ketamine on several facets of neurocognitive functioning related to driving performance, as well as explicit assessments of driving impairment.
This study aims to assess the effect of three doses of intravenously (IV) administered ketamine infusions delivered in an increasing step-dose manner on measures of higher-order cognitive processes and driving simulator performance. We will also assess the relatedness between the level of ketamine in the blood samples and over the 8 hour testing session in order to assess the relationship between ketamine blood concentration, cognitive function and driving ability. We also want to monitor the relationship between the treatment (ketamine infusion low, medium or high dose) and levels of subjective alertness over time, and how this relates to performance outcomes on the cognitive and driving tasks.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 69350 0
Prof Yahya Shehabi
Address 69350 0
Program Director Critical Care
Monash Medical Centre
246 Clayton Road
Clayton Victoria 3168
Country 69350 0
Australia
Phone 69350 0
+61 3 9594 2730
Fax 69350 0
Email 69350 0
yahya.shehabi@monashhealth.org
Contact person for public queries
Name 69351 0
Dr Amie Hayley
Address 69351 0
Mail H20
Swinburne University of Technology,
Faculty of Health, Arts and Design School of Health Sciences
Centre for Human Psychopharmacology
PO Box 218
Hawthorn,
Victoria, 3122 Australia
Country 69351 0
Australia
Phone 69351 0
+61 3 9214 5585
Fax 69351 0
Email 69351 0
ahayley@swin.edu.au
Contact person for scientific queries
Name 69352 0
Dr Amie Hayley
Address 69352 0
Mail H20
Swinburne University of Technology,
Faculty of Health, Arts and Design School of Health Sciences
Centre for Human Psychopharmacology
PO Box 218
Hawthorn,
Victoria, 3122 Australia
Country 69352 0
Australia
Phone 69352 0
+61 3 9214 5585
Fax 69352 0
Email 69352 0
ahayley@swin.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results ā€“ basic reporting
Results ā€“ plain English summary