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Trial registered on ANZCTR


Registration number
ACTRN12623000446662
Ethics application status
Approved
Date submitted
17/04/2023
Date registered
2/05/2023
Date last updated
27/07/2023
Date data sharing statement initially provided
2/05/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 2 Randomised Controlled Trial of Sodium Selenate as a Disease Modifying Treatment for Chronic Drug-resistant Temporal Lobe Epilepsy - The SeLECT Study
Scientific title
A Phase 2 Randomised Controlled Trial of Sodium Selenate as a Disease Modifying Treatment for Chronic Drug-resistant Temporal Lobe Epilepsy
Secondary ID [1] 309397 0
None
Universal Trial Number (UTN)
U1111-1291-3258
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mesial temporal lobe epilepsy 329627 0
Condition category
Condition code
Neurological 326553 326553 0 0
Epilepsy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Sodium selenate, 15mg three times a day, 26 weeks, oral tablet. Participants will be required to return unused tablets to site each visit to monitor compliance with dosing regimen.
Intervention code [1] 325833 0
Treatment: Drugs
Comparator / control treatment
Placebo (microcrystalline cellulose), three times a day, 26 weeks, oral tablet
Control group
Placebo

Outcomes
Primary outcome [1] 334393 0
Change in desirability of outcome (DOOR) score between active and placebo groups.

The DOOR-epilepsy framework is a consumer co-designed outcome measure combining variables of seizure frequency, adverse events, quality of life, and medication burden into a single score.
Timepoint [1] 334393 0
Change from baseline to 52 weeks post initiation of treatment.
Secondary outcome [1] 420801 0
Seizure frequency assessed by diary cards.
Timepoint [1] 420801 0
Change from baseline to 52 weeks post initiation of treatment.
Secondary outcome [2] 420803 0
Change in psychiatric comorbidities assessed by the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E)

The NDDI-E is a questionnaire designed to screen for depression (including depression severity).
Timepoint [2] 420803 0
Change from baseline to 52 weeks post initiation of treatment.
Secondary outcome [3] 420804 0
The anti-seizure medication burden assessed by The Liverpool Adverse Event Profile (LAEP).

The LAEP is a questionnaire used to assess the presence and severity of common adverse effects associated with anti-seizure medications.
Timepoint [3] 420804 0
Change from baseline to 52 weeks post initiation of treatment.
Secondary outcome [4] 420805 0
Change in global cognitive function assessed by the Australian Epilepsy Project (AEP) cognitive battery. The AEP cognitive battery is a series of cognitive tests that are specifically designed to assess cognitive deficits that are common in patients with epilepsy.
Timepoint [4] 420805 0
Change from baseline to 52 weeks post initiation of treatment.
Secondary outcome [5] 420806 0
Change in quality of life assessed by the Quality of Life in Epilepsy Inventory-31 (QOLIE-31).

The QOLIE-31 is an assessment tool designed to evaluate various health concepts associated with epilepsy, such as emotional well-being, seizure-related concerns, energy and fatigue, cognitive function, medication effects, and overall quality of life.
Timepoint [5] 420806 0
Change from baseline to 52 weeks post initiation of treatment.
Secondary outcome [6] 420807 0
Safety will be assessed based on the frequency and severity of adverse events (AEs) as measured by diary cards and face to face report with patients at clinic visits.

Relevant AEs associated with sodium selenate, such as nail changes and hair loss, have been selected for inclusion on the diary cards. Other changes from baseline will be monitored in clinic by reviewing medical history, conducting physical and neurological examinations in accordance with general medical practice, assessing vital signs (including weight using digital scales, blood pressure using a sphygmomanometer, heart rate using a digital heart rate monitor, and temperature using a thermometer), conducting a 12-lead ECG, and analyzing haematology, biochemistry, and urinalysis. Additionally, the Columbia Suicide Severity Rating Scale (C-SSRS) will be used to detect suicidal ideation or suicidal behaviour. All adverse events will be assessed in accordance with the Common Terminology Criteria for Adverse Events (CTCAE).
Timepoint [6] 420807 0
Cumulative from baseline to week 52 post-initiation of treatment.
Secondary outcome [7] 420855 0
Change in psychiatric comorbidities assessed by the General Anxiety Disorder-7 (GAD-7).

The GAD-7 is a questionnaire designed to screen for anxiety.
Timepoint [7] 420855 0
Change from baseline to 52 weeks post initiation of treatment.
Secondary outcome [8] 420856 0
Change in desirability of outcome (DOOR) score between active and placebo groups.

The DOOR-epilepsy framework is a consumer co-designed outcome measure combining variables of seizure frequency, adverse events, quality of life, and medication burden into a single score.
Timepoint [8] 420856 0
Change from baseline to 26 weeks post initiation of treatment.
Secondary outcome [9] 420857 0
Seizure frequency assessed by diary cards.

Timepoint [9] 420857 0
Change from baseline to 26 weeks post initiation of treatment.
Secondary outcome [10] 420858 0
Change in psychiatric comorbidities assessed by the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E)

The NDDI-E is a questionnaire designed to screen for depression (including depression severity).
Timepoint [10] 420858 0
Change from baseline to 26 weeks post initiation of treatment.
Secondary outcome [11] 420859 0
The anti-seizure medication burden assessed by The Liverpool Adverse Event Profile (LAEP).

The LAEP is a questionnaire used to assess the presence and severity of common adverse effects associated with anti-seizure medications.
Timepoint [11] 420859 0
Change from baseline to 26 weeks post initiation of treatment.
Secondary outcome [12] 420860 0
Change in global cognitive function assessed by the Australian Epilepsy Project (AEP) cognitive battery. The AEP cognitive battery is a series of cognitive tests that are specifically designed to assess cognitive deficits that are common in patients with epilepsy.
Timepoint [12] 420860 0
Change from baseline to 26 weeks post initiation of treatment.
Secondary outcome [13] 420861 0
Change in psychiatric comorbidities assessed by the General Anxiety Disorder-7 (GAD-7)

The GAD-7 is a questionnaire designed to screen for anxiety.
Timepoint [13] 420861 0
Change from baseline to 26 weeks post initiation of treatment.
Secondary outcome [14] 421168 0
Epileptiform discharge assessed by ambulatory 24 hour EEG recording.

Timepoint [14] 421168 0
Change from baseline to 52 weeks post initiation of treatment.
Secondary outcome [15] 421169 0
Epileptiform discharge assessed by ambulatory 24 hour EEG recording.
Timepoint [15] 421169 0
Change from baseline to 26 weeks post initiation of treatment.
Secondary outcome [16] 421186 0
Tolerability will be assessed by measure of withdrawal rates from the study by an audit of study records.
Timepoint [16] 421186 0
Cumulative from baseline to week 52 post-initiation of treatment.

Eligibility
Key inclusion criteria
1. Male or female (aged 18-75 years).
2 Subjects must have a diagnosis of drug-resistant temporal lobe epilepsy (TLE) for at least 2 years at the time of screening.
3. Participants must have 4 or more countable seizures per month (any combination of focal impaired awareness seizures, focal to bilateral tonic clonic seizures or focal aware seizures with motor symptoms)
4. Participants must be on 1 or more stable ASM for a period of >8 weeks
5. Participants must have interictal epileptiform discharges (average >1 spike/hr) on baseline 24-hour EEG localising to one or both temporal lobes without extratemporal discharges or seizures
6. All participants of reproductive potential must be using effective contraception for the duration of the trial and for 4 weeks following cessation of the investigational medicinal product (IMP). Female participants of non-childbearing potential must be either surgically sterile (hysterectomy and/or oophorectomy) or postmenopausal at least 1 year. All female participants must have a negative plasma hCG pregnancy test at screening.
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Participants with extra-temporal or genetic generalised epilepsy
2 Current or historic substance use disorder (as per DSM V criteria).
2. Women who are pregnant or lactating and persons of reproductive potential unwilling/unable to take adequate contraceptive precaution for the duration of the study are excluded.
3. Participants who have recently (within 3 months of screening) participated in another interventional clinical trial are excluded.
4. Participants who have recent (within 5 years) history of psychogenic non-epileptic seizures, or who have significant medical or neurological disease other than epilepsy that is not adequately controlled by therapy are excluded.
5. Participants who have commenced medications with a known effect on mood, cognition or seizures within 4 weeks of screening are also excluded.
6. Participants with a known sensitivity to selenium, sodium selenate, any medicine or vitamin containing sodium selenate, similar agents or any of the excipients (including microcrystalline cellulose) used are excluded.


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)
Allocation involves contacting the holder of the allocation schedule who was "off-site" or at central administration site.
(central randomisation by phone/fax/computer)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software

Participants will be stratified based on their seizure frequency during the screening period (greater or fewer than 8 seizures/month) and the presence or absence of hippocampal/mesial temporal sclerosis.
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
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
Statistical power has thus been determined on the primary outcome variable (change in DOOR scale score). A sample size of 108 patients would yield power of 0.8 to observe such hypothesized treatment effect against the null hypothesis of no treatment effect (Win Ratio greater than or equal to 1) assuming two-sided alpha level of 0.05. In order to account for 10-15% potential losses due to screen failures and non-evaluable data the final sample size for this study is set as 124 participants.

Secondary endpoints will utilise generalised linear models (GLMs) to assess group level differences between baseline and week 26 to assess anti-seizure effects, and baseline and week 52 to assess anti-epileptogenesis effects. Differences in seizure frequency on seizure diaries, epileptiform discharge frequency on 24 hour EEGs, NDDI-E score, GAD-7 score, QOLIE-31 score, NIH toolbox composite score, LAEP score will all be compared between treatment and placebo groups. Baseline measures will be included in the models as covariates and the model will estimate the adjusted mean change (with 95% confidence intervals) as a marker of treatment.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/10/2023
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
124
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA,VIC
Recruitment hospital [1] 24523 0
The Alfred - Melbourne
Recruitment hospital [2] 24524 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [3] 24525 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [4] 24526 0
Eastern Health - Box Hill
Recruitment hospital [5] 24527 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [6] 24528 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [7] 24530 0
Mater Adult Hospital - South Brisbane
Recruitment hospital [8] 24531 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [9] 24542 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 40115 0
3004 - Melbourne
Recruitment postcode(s) [2] 40116 0
3050 - Parkville
Recruitment postcode(s) [3] 40117 0
3084 - Heidelberg
Recruitment postcode(s) [4] 40118 0
3128 - Box Hill
Recruitment postcode(s) [5] 40119 0
3065 - Fitzroy
Recruitment postcode(s) [6] 40120 0
4029 - Herston
Recruitment postcode(s) [7] 40122 0
4101 - South Brisbane
Recruitment postcode(s) [8] 40123 0
6009 - Nedlands
Recruitment postcode(s) [9] 40136 0
2145 - Westmead

Funding & Sponsors
Funding source category [1] 313592 0
Government body
Name [1] 313592 0
NHMRC (MRFF)
Country [1] 313592 0
Australia
Primary sponsor type
Hospital
Name
Alfred Health
Address
55 Commercial Road
Melbourne
3004 VIC
Country
Australia
Secondary sponsor category [1] 315377 0
None
Name [1] 315377 0
Address [1] 315377 0
Country [1] 315377 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312769 0
Alfred Health HREC
Ethics committee address [1] 312769 0
55 Commercial Road
Melbourne
VIC 3004
Ethics committee country [1] 312769 0
Australia
Date submitted for ethics approval [1] 312769 0
22/05/2023
Approval date [1] 312769 0
11/07/2023
Ethics approval number [1] 312769 0

Summary
Brief summary
This study will investigate a new drug, sodium selenate, for the treatment of drug-resistant temporal lobe epilepsy (TLE). Up to 124 patients with TLE will be recruited in to the study. Half of the patients will receive 26 weeks of treatment with sodium selenate (15 mg three times a day), and the other half a placebo (a sugar pill). The primary outcome will be the a consumer co-designed DOOR-epilepsy rank, combining change in seizure frequency, adverse events, quality of life and ASM burden measures into a single outcome measure, compared between treatment and placebo groups over the whole 52 week period. Secondary outcomes include measures of seizures, epileptiform activity, cognitive and, neuropsychiatric outcome measures, quality of life, and medication burden at the end of 26 and 52 weeks (compared to baseline). Other measures will include safety and tolerability and exploratory biomarkers of treatment response.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 125846 0
Prof Terence O'Brien
Address 125846 0
Level 6, The Alfred Centre
99 Commercial Road
Melbourne
3004 VIC
Country 125846 0
Australia
Phone 125846 0
+61418370566
Fax 125846 0
Email 125846 0
[email protected]
Contact person for public queries
Name 125847 0
Lucy Vivash
Address 125847 0
Level 6, The Alfred Centre
99 Commercial Road
Melbourne
3004 VIC
Country 125847 0
Australia
Phone 125847 0
+61 3 9903 0860
Fax 125847 0
Email 125847 0
[email protected]
Contact person for scientific queries
Name 125848 0
Lucy Vivash
Address 125848 0
Level 6, The Alfred Centre
99 Commercial Road
Melbourne
3004 VIC
Country 125848 0
Australia
Phone 125848 0
+61 3 9903 0860
Fax 125848 0
Email 125848 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All deidentified trial data will be publicly available, after publication of study results.
Additionally - biospecimens will be available to genuine researchers upon request (and justification) to the study team
When will data be available (start and end dates)?
Immediately following publication of study results, no end date
Available to whom?
Deidentified trial data will be publically available to anyone who wishes to access it.
Biospecimen data will be made available to researchers who supply a proposal to the study team/ lead HREC. Not all biospecimen data will be freely available due to participants being given the option of specified/extended/unspecified consent for the long-term use of these data.
Available for what types of analyses?
Main trial data will be available for any types of analyses.
Biospecimen data will be given to achieve the aims of submitted proposals in alignment with any restrictions placed on future use of data
How or where can data be obtained?
Upon direct request to the study team (see contact information page for phone/emails of PI and PM) a summary of available data will be made available on the Monash University Website.
PI: [email protected]
PM: [email protected]


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
18875Study protocol  [email protected]
18876Statistical analysis plan  [email protected]
18877Informed consent form    To be supplied upon HREC approval
18878Ethical approval    To be supplied upon HREC approval



Results publications and other study-related documents

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