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Trial registered on ANZCTR


Registration number
ACTRN12618000193279
Ethics application status
Approved
Date submitted
31/01/2018
Date registered
7/02/2018
Date last updated
8/01/2019
Date data sharing statement initially provided
8/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A study of the connectivity measures of a resting-state brain network in patients with Epilepsy.
Scientific title
Assessing connectivity measures and neurotransmitter concentrations of the Default Mode Network (DMN) via functional Magnetic Resonance Imaging (fMRI) and Magnetic Resonance Spectroscopy (MRS) in patients with Epilepsy.
Secondary ID [1] 293920 0
Nil known.
Universal Trial Number (UTN)
U1111-1208-7440
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Epilepsy 306407 0
Condition category
Condition code
Neurological 305497 305497 0 0
Epilepsy

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Participants will undergo a single 7-Tesla MRI scan that will consist of a high-resolution anatomical scan, magnetic resonance spectroscopy (MRS), and functional magnetic resonance imaging (fMRI). The total scanning time will be around 20 minutes.
Intervention code [1] 300190 0
Diagnosis / Prognosis
Comparator / control treatment
The control group will consist of healthy volunteers previously scanned in a different study("Development of High Field Magnetic Resonance Imaging Methods
and Protocols" at The University of Melbourne) between 05/2017 and 01/2018.
Control group
Historical

Outcomes
Primary outcome [1] 304627 0
Glutamate concentrations as measured by MRS of the Posterior Cingulate Cortex.
Timepoint [1] 304627 0
Single scan, concomitant with fMRI.
Primary outcome [2] 304628 0
GABA concentration as measured by MRS of the Posterior Cingulate Cortex
Timepoint [2] 304628 0
Single scan, concomitant with fMRI.
Primary outcome [3] 304684 0
Fisher-transformed correlation coefficient values between regions of the Default Mode Network and between the Posterior Cingulate Cortex to all brain regions via resting state fMRI.
Timepoint [3] 304684 0
Single scan, concomitant with MRS.
Secondary outcome [1] 342624 0
Duration of epilepsy - will be defined from first seizure, self-reported by study participants.
Timepoint [1] 342624 0
At enrolment.
Secondary outcome [2] 342625 0
Seizure frequency. It will be self-reported by the study participants and scored from 0 to 4:
0 = seizure-free (no seizures during the previous 3 months);
1 = =1 seizures during the last 3 months, but not within the past month;
2 = =1 seizures per month;
3 = =1 seizures per week;
4 = =1 seizures per day.
The past seizure frequency will be assessed during a period of only 3 months to reduce recall bias.
Timepoint [2] 342625 0
At enrolment.
Secondary outcome [3] 342626 0
EEG characteristics - distribution, type and frequency of epileptiform discharges.
Timepoint [3] 342626 0
EEG results will be checked immediately following enrolment.
Secondary outcome [4] 342627 0
Number of antiepileptic medications being used by the participant as self-reported by the participant (presently used at the time of enrolment).
Timepoint [4] 342627 0
At enrolment.

Eligibility
Key inclusion criteria
Diagnosis of Idiopathic Generalised Epilepsy (IGE) or Temporal Lobe Epilepsy (TLE), right-handedness, able to provide written informed consent in English.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Any contraindication to a 7-Tesla MRI scan (a detailed safety questionnaire will be used).

Study design
Purpose
Screening
Duration
Cross-sectional
Selection
Convenience sample
Timing
Prospective
Statistical methods / analysis
After data acquisition the MRS metabolites will be quantified using the LCModel software package. Pre-processing of the fMRI data will be performed using the SPM12 software (Wellcome Trust Centre for Neuroimaging, UCL) and CONN toolbox version 17 (McGovern Institute of Brain Research, MIT). Predefined Regions-Of-Interest (ROIs) from the CONN-fMRI Functional Connectivity toolbox will be chosen based on a prior study as seeds to create connectivity maps of the default mode network.
Seed-to-voxel and ROI-to-ROI functional connectivity maps will be created for each subject. Maps of functional connectivity will be calculated by computing Pearson’s product moment correlation between each pair of ROIs (ROI-to-ROI) and between each ROI and all acquired voxels (Seed-to-voxel). For each ROI the values will be the mean of all voxels within the ROI. Correlation maps will be converted to z-maps using Fisher’s r-to-z transformation.
Results of exploratory analyses will be considered significant if they survived correction for multiple comparisons (FDR = 0.05).
Mean differences between clinical characteristics, GABA and glutamate concentration measurements and parameters of functional connectivity will be calculated using Student’s t-test for continuous variables and chi-square test or Fisher’s exact test for categorical data. The Mann–Whitney U-test will be used for nonparametric evaluations of the mean differences between the groups regarding seizure frequency and drug treatment. The level of significance will be set to a = 0.05 (two sided). Subgroup analysis of right versus left TLE and drug-responsive versus drug-resistant IGE patients will be performed.

Recruitment
Recruitment status
Recruiting
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
Recruitment hospital [1] 9921 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [2] 9922 0
The Alfred - Prahran
Recruitment postcode(s) [1] 18730 0
3050 - Parkville
Recruitment postcode(s) [2] 18731 0
3004 - Prahran

Funding & Sponsors
Funding source category [1] 298549 0
Hospital
Name [1] 298549 0
The Royal Melbourne Hospital Neuroscience Foundation
Address [1] 298549 0
4 East, Main Building
The Royal Melbourne Hospital
300 Grattan Street, Parkville 3050, VIC
Country [1] 298549 0
Australia
Primary sponsor type
Hospital
Name
The Royal Melbourne Hospital
Address
300 Grattan Street
Parkville 3050, VIC
Country
Australia
Secondary sponsor category [1] 297695 0
None
Name [1] 297695 0
Address [1] 297695 0
Country [1] 297695 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299518 0
Melbourne Health Human Research Ethics Committee
Ethics committee address [1] 299518 0
Office for Research
Level 2 South West
The Royal Melbourne Hospital
300 Grattan Street
Parkville 3050, VIC
Ethics committee country [1] 299518 0
Australia
Date submitted for ethics approval [1] 299518 0
25/10/2017
Approval date [1] 299518 0
09/01/2018
Ethics approval number [1] 299518 0
HREC/17/MH/341

Summary
Brief summary
Despite adequate treatment with two or more antiepileptic drugs, about one third of patients diagnosed as having epilepsy are not seizure-free. It is imperative to promptly diagnose and manage these patients, as recurrent seizures are correlated with important clinical, cognitive and socioeconomic consequences.
The current project aims to recruit patients with temporal lobe epilepsy and idiopathic generalised epilepsy, and to study the connectivity measures of a resting-state
brain network called the Default Mode Network (DMN) in these patients via functional Magnetic Resonance Imaging (fMRI). In addition, the concentration of various metabolites
in one the key nodes of this network will be measured via Magnetic Resonance Spectroscopy (MRS).
The results of these scans will be compared to data already collected from healthy controls to create a predictive model that will facilitate the diagnosis of patients with different types of epilepsy, and to distinguish between drug-resistant and drug-responsive
cases, via a brief MRI scan.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 80694 0
Dr Ofer Gonen
Address 80694 0
Neurology Department
The Royal Melbourne Hospital
300 Grattan Street
Parkville 3050, VIC
Country 80694 0
Australia
Phone 80694 0
+61 3 93427722
Fax 80694 0
+61 3 93428628
Email 80694 0
ogonen@gmail.com
Contact person for public queries
Name 80695 0
Dr Ofer Gonen
Address 80695 0
Neurology Department
The Royal Melbourne Hospital
300 Grattan Street
Parkville 3050, VIC
Country 80695 0
Australia
Phone 80695 0
+61 3 93427722
Fax 80695 0
+61 3 93428628
Email 80695 0
ogonen@gmail.com
Contact person for scientific queries
Name 80696 0
Dr Ofer Gonen
Address 80696 0
Neurology Department
The Royal Melbourne Hospital
300 Grattan Street
Parkville 3050, VIC
Country 80696 0
Australia
Phone 80696 0
+61 3 93427722
Fax 80696 0
+61 3 93428628
Email 80696 0
ogonen@gmail.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
Informed consent form
Summary results
No Results