Phase II randomised placebo-controlled trial of sodium selenate as a disease-modifying treatment in chronic drug-resistant temporal lobe epilepsy: the SeLECT study protocol

Abstract

Introduction: Epilepsy is one of the most common neurological conditions worldwide. Despite many antiseizure medications (ASMs) being available, up to one-third of patients do not achieve seizure control. Preclinical studies have shown treatment with sodium selenate to have a disease-modifying effect in a rat model of chronic temporal lobe epilepsy (TLE).

Aim: This randomised placebo-controlled trial aims to evaluate the antiseizure and disease-modifying effects of sodium selenate in people with drug-resistant TLE.

Methods: This will be a randomised placebo-controlled trial of sodium selenate. One hundred and twenty-four adults with drug-resistant TLE and ≥4 countable seizures/month will be recruited. Outcomes of interest will be measured at baseline, week 26 and week 52 and include an 8-week seizure diary, 24-hour electroencephalogram and cognitive, neuropsychiatric and quality of life measures. Participants will then be randomised to receive a sustained release formulation of sodium selenate (initially 10 mg three times a day, increasing to 15 mg three times a day at week 4 if tolerated) or a matching placebo for 26 weeks.

Outcomes: The primary outcome will be a consumer codesigned epilepsy-Desirability of Outcome Rank (DOOR), combining change in seizure frequency, adverse events, quality of life and ASM burden measures into a single outcome measure, compared between treatment arms over the whole 52-week period. Secondary outcomes will compare baseline measures to week 26 (antiseizure) and week 52 (disease modification). Exploratory measures will include biomarkers of treatment response.

Ethics and dissemination: The study has been approved by the lead site, Alfred Hospital Ethics Committee (594/20). Each participant will provide written informed consent prior to any trial procedures. The results of the study will be presented at national and international conferences, published in peer-reviewed journals and disseminated through consumer organisations.

Conclusion: This study will be the first disease-modification randomised controlled trial in patients with drug-resistant TLE.

Trial registration number: ANZCTR; ACTRN12623000446662.

Keywords: clinical trial; epilepsy; randomized controlled trial.

Figure 1

Overall study timeline. Baseline and outcome assessments consist of seizure diaries, review of medication burden and adverse effects, neuropsychiatry questionnaires (General Anxiety Disorder 7 and Neurological Disorders Depression Inventory for Epilepsy), Quality of Life Questionnaire (Quality of Life in Epilepsy Inventory 31), Australian Epilepsy Project neurocognitive battery and 24 hour ambulatory EEG recording. Biomarkers include measures of serum tau, total tau, neurofilament light chain and DNA (telomere length).