None listed
Conditions
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.
Interventions
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.
Sponsors
Alfred Health
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female (18-75 years). All participants with reproductive potential must be using effective contraception for the duration of the trial and for 12 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. 2. Participants must have a diagnosis of drug resistant TLE (>2 years) established in accordance with the ILAE criteria [1]. 3. Participants must have greater than or equal to 4 countable seizures per month (any combination of focal impaired awareness seizures, focal to bilateral tonic clonic seizures or focal aware seizures with motor symptoms) and be on greater than or equal to 1 stable ASM for a period of >8 weeks. 4. Participants must have a 24-hour ambulatory EEG during the screening period, demonstrating localisation to one or both temporal lobes without extratemporal discharges or seizures. IEDs or seizures which spread outside of the temporal lobe will not be exclusionary provided it can be demonstrated they initiate from the temporal lobe. 5. Participants with vagal nerve stimulators (>6 months since VNS surgery, stable settings >8 weeks) are eligible, as are participants who have had prior epilepsy surgery (>12 months prior to screening). 6. Participants must have a historic epilepsy protocol MRI which identifies no potentially epileptogenic lesion other than hippocampal or mesial temporal sclerosis. Presence of an encephalocele will not be exclusionary provided the investigator is confident it is not the underlying cause of epilepsy. 7. Written informed consent must be obtained from the participant.
Exclusion criteria
Exclusion criteria 1. Participants with extratemporal or genetic generalised epilepsy 2. Participants who have a recent (within 5 years) history of psychogenic non-epileptic seizures 3. Participants with a current or history of substance use disorder (as defined by DSM-V). Recreational use or treatment with CBD oil are allowed. 4. Participants who are pregnant or lactating and persons of reproductive potential unwilling/unable to take adequate contraceptive precautions for the duration of the study are excluded. 5. Subject has 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. 6. Participants who have recently (within 3 months of screening) participated in another interventional clinical trial 7. Subject has a significant medical or neurological disease, with the exception of TLE that: - is not adequately controlled by therapy; and/or in the opinion of the investigator may interfere with the patient’s ability to complete the study or compromise their safety 8. Subject has current evidence of unstable diabetes. 9. Subject has significant impairment of any of the following for the age of the participant, which may compromise safety of the participant/validity of the data: - Renal function (i.e., estimated glomerular filtration rate (eGFR) <30 ml/min) - Hepatic function (i.e., abnormal liver function tests 2 x upper limit of normal) - Haematological function. 10. Subject is currently taking any of the following: - Digoxin, phenobarbitone, warfarin or any other medication that has a narrow margin between effective dose and toxic dose or between effective dose and ineffective dose, where the participant would be at risk if the levels were elevated or fell due to interaction with sodium selenate. - Subject has started taking or changed their dose of other medication known to have an effect on mood or cognition within the 4 weeks prior to the Screening Visit (Visit 1). Examples of such drugs include: - Anticholinergics, for example ipratropium, oxitropium or tiotropium bromide - Hypnotics, sedatives and anxiolytics, for example barbiturates, benzodiazepines, serotonin 1A agonists, hydroxyzine, zolpidem or zopiclone with the exception of rescue medications. No cognitive testing should occur within 24 hours of benzodiazepine use. - Antidepressants, for example tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitor (MAOIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), noradrenergic and specific serotonergic antidepressants, buspirone, reboxetine or trazodone - Antipsychotics, for example butyrophenones, phenothiazines, thioxanthenes, amisulpride, aripiprazole, clozapine, olanzapine, paliperidone or quetiapine - Memory-enhancing drugs, for example aniracetam, oxiracetam, piracetam or pramiracetam
Outcome results
None listed