Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616000281493
Ethics application status
Approved
Date submitted
29/02/2016
Date registered
3/03/2016
Date last updated
25/10/2021
Date data sharing statement initially provided
25/10/2021
Date results information initially provided
25/10/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
The use of simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) to monitor the effects of ketamine and midazolam on brain activity
Scientific title
The use of simultaneous EEG and fMRI to monitor the effects of ketamine and midazolam on brain activity in healthy adult males
Secondary ID [1] 288646 0
None
Universal Trial Number (UTN)
U1111-1177-3828
Trial acronym
EFKAM
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Healthy volunteers: Anaesthetic sedation 297827 0
Condition category
Condition code
Anaesthesiology 298001 298001 0 0
Anaesthetics
Neurological 298025 298025 0 0
Studies of the normal brain and nervous system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Ketamine IV. – bolus dose 0.25mg/kg then infusion at up to 0.25 mg/kg/hr (up to 1hr)
Midazolam IV – bolus dose 0.3mg/kg then infusion at up to 0.03 mg/kg/hr (up to 1hr)

Drug administration will be terminated at the completion of all EEG/fMRI scanning.
Infusion doses may be reduced at the discretion of the attending clinician if excessive sedation occurs.

A 3 day minimum washout between sessions will be employed.

All doses will be administered by study staff with doses logged in the trial master file
Intervention code [1] 294061 0
Treatment: Drugs
Comparator / control treatment
Cannula inserted no infusion
Control group
Placebo

Outcomes
Primary outcome [1] 297515 0
Power spectral density of the EEG
Timepoint [1] 297515 0
0-10 minutes post administration
Secondary outcome [1] 321278 0
Functional connectivity measured with functional magnetic resonance imaging (fMRI)
Timepoint [1] 321278 0
0-10 minutes post administration

Eligibility
Key inclusion criteria
*Participant is willing and able to give informed consent for participation in the study
*In the Investigators’ opinion, is able and willing to comply with all study requirements
Minimum age
18 Years
Maximum age
45 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
*Cardiovascular conditions including abnormal heart rate and blood pressure checked at screening.
*Participants who have participated in another research study involving an investigational product in the past 12 weeks.
*History of psychosis or personality disorder.
*Any unstable medical or neurologic condition.
*Substance abuse or dependence in previous 6 months.
*Any history of abuse of ketamine or benzodiazepenes.
*Contraindication to the use of ketamine/midazolam according to manufacturer guidelines.
*Body-weight <50kg or >120kg.
*BMI <18.5 or > 30
* Failure of the Health Questionnaire section of the “Anaesthesia assessment patient questionnaire”.
*Any other condition judged by the treating clinician as likely to impact on the ability of the participant to complete the study.
*Regular use of any medication deemed to be contraindicating as judged by the attending study physicians (e.g. benzodiazepenes / sedatives / sleeping agents / NMDA antagonists).
*Inability to speak or read English.
*Contraindications for MRI scanning
*Needle phobia
*History of claustrophobia

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
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
28/03/2016
Actual
24/03/2016
Date of last participant enrolment
Anticipated
Actual
30/08/2016
Date of last data collection
Anticipated
Actual
15/12/2016
Sample size
Target
30
Accrual to date
Final
30
Recruitment outside Australia
Country [1] 7630 0
New Zealand
State/province [1] 7630 0

Funding & Sponsors
Funding source category [1] 293005 0
Commercial sector/Industry
Name [1] 293005 0
F Hoffmann La Roche
Country [1] 293005 0
Switzerland
Primary sponsor type
University
Name
The University of Auckland
Address
Private Bag 92019
Auckland 1142
Country
New Zealand
Secondary sponsor category [1] 291783 0
None
Name [1] 291783 0
Address [1] 291783 0
Country [1] 291783 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294514 0
Central HDEC
Ethics committee address [1] 294514 0
Ministry of Health
Freyberg Building
20 Aitken Street
PO Box 5013
Wellington
6011
Ethics committee country [1] 294514 0
New Zealand
Date submitted for ethics approval [1] 294514 0
19/02/2016
Approval date [1] 294514 0
08/03/2016
Ethics approval number [1] 294514 0

Summary
Brief summary
EEG and fMRI are two of the principal techniques currently used to measure human brain function. However, EEG and fMRI measure different aspects of brain activity and it is unclear how the measures relate to each other. Both these techniques have the potential to provide important information in understanding how central nervous system medicines alter brain function. However, the results of previous drug studies where these two techniques are
recorded separately are difficult to reconcile. While technically challenging it is now possible to simultaneously record EEG/fMRI. Recording simultaneous EEG/fMRI in the context of drug studies may help to resolve issues raised by previous studies. In this project we propose to record simultaneous EEG/fMRI in healthy volunteer participants while they are given two commonly used anaesthetic drugs, midazolam and ketamine. Our study aims to reconcile previous results in the literature and provide a template example for how future drug imaging studies (involving patients and new medications) might be conducted.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 63978 0
Dr Suresh Muthukumaraswamy
Address 63978 0
School of Pharmacy
The University of Auckland
Private Bag 92019
Auckland 1142
Country 63978 0
New Zealand
Phone 63978 0
+64 9373 7599 ext:85398
Fax 63978 0
Email 63978 0
[email protected]
Contact person for public queries
Name 63979 0
Dr Suresh Muthukumaraswamy
Address 63979 0
School of Pharmacy
The University of Auckland
Private Bag 92019
Auckland 1142
Country 63979 0
New Zealand
Phone 63979 0
+64 9373 7599 ext:85398
Fax 63979 0
Email 63979 0
[email protected]
Contact person for scientific queries
Name 63980 0
Dr Suresh Muthukumaraswamy
Address 63980 0
School of Pharmacy
The University of Auckland
Private Bag 92019
Auckland 1142
Country 63980 0
New Zealand
Phone 63980 0
+64 9373 7599 ext:85398
Fax 63980 0
Email 63980 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes Forsyth, A., R. McMillan, D. Campbell, G. Malpas, ... [More Details] 370230-(Uploaded-26-05-2021-05-21-58)-Journal results publication.pdf

Documents added automatically
No additional documents have been identified.