None listed
Conditions
Brief summary
Lennox-Gastaut syndrome (LGS) is a treatment-resistant form of childhood-onset generalised epilepsy, defined by multiple seizure types including tonic seizures, specific EEG abnormalities, and cognitive impairment. Anti-seizure medications are only partially effective and resective surgery is rarely an option, meaning new treatment approaches are needed. Deep brain stimulation (DBS) is an emerging treatment for drug-resistant epilepsies, which aims to modulate neuronal excitability across the distributed networks that underpin generalised epilepsies. Prior uncontrolled studies have reported seizure reductions following Deep Brain Stimulation (DBS) in patients with Lennox-Gastaut syndrome (LGS), but data from randomised controlled studies are lacking. We aimed to formally assess the efficacy and safety of DBS to the centromedian thalamic nucleus (CM) for treatment of LGS. Electrical Stimulation of the Thalamus for Epilepsy of Lennox-Gastaut Phenotype (ESTEL) is the first randomised, double-blind, controlled study to evaluate the efficacy and safety of CM-DBS in a carefully characterised group of young adults with LGS. Due to the poor correlation between diary seizure counts and objective seizure frequencies, we also measure electrographic seizures (on 24-hour ambulatory EEG) at key timepoints (baseline, post-implantation/pre-stimulation, and post-stimulation. We perform cognitive assessments at these same timepoints and report safety outcomes in the 20 participants. We hypothesise that the proportion of participants with a 50% or greater reduction in seizures will be higher in those receiving 3-months of CM-DBS, compared to control participants (i.e., no stimulation).
Interventions
Prospective, double-blind, randomised study of continuous, cycling stimulation of Centromedian nucleus Deep Brain Stimulation (CM-DBS), in patients with Lennox-Gastaut Syndrome (LGS). All participants (n=20) will undergo bilateral CM-DBS insertion by a single neurosurgeon at Austin Health (Austin Health Human Research Ethics approval number HREC/16/Austin/139). Following 3-month pre- and post-implantation periods, half receive 3-months stimulation (blinded phase), then all receive 3-months stimu
Prospective, double-blind, randomised study of continuous, cycling stimulation of Centromedian nucleus Deep Brain Stimulation (CM-DBS), in patients with Lennox-Gastaut Syndrome (LGS). All participants (n=20) will undergo bilateral CM-DBS insertion by a single neurosurgeon at Austin Health (Austin Health Human Research Ethics approval number HREC/16/Austin/139). Following 3-month pre- and post-implantation periods, half receive 3-months stimulation (blinded phase), then all receive 3-months stimulation (unblinded phase) i.e., early treatment group receives 6-months of stimulation and delayed treatment group receive 3-months of stimulation throughout the study. Randomisation/stimulation adjustments are by a single unblinded programmer, while clinical assessments and data collation are performed by separate clinicians blinded to treatment group and voltage settings. Participants and caregivers are also blinded to stimulation group/settings. Stimulation parameters: Medtronic Activa PC; 3389 leads; duty cycle stimulation, 1 min on/5 mins off; 145Hz, 90usec pulse width, 2.5V or highest tolerated.
Sponsors
Associate Professor John ARCHER
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
15 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
i) an electroclinical diagnosis of LGS; ii) generalised paroxysmal fast activity (GPFA) and slow spike-and-wave (SSW) on interictal EEG; and iii) generalised tonic seizures documented on prior video-EEG monitoring or clearly described by a reliable eyewitness
Exclusion criteria
i) participants with elevated risks for bleeding; ii) cerebral anatomical variations precluding safe CM-DBS implantation; iii) predominant seizure type being focal impaired awareness seizures; iv) current or prior psychogenic non-epileptic seizures
Outcome results
None listed