Clinical trial NCT06789497: The GABAergic Inhibitory System in Drug Resistant Epilepsy
Official title: Lovastatin Modulation of the Inhibition-excitation Balance in Temporal Lobe Onset Drug Resistant Epilepsy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Drug Resistant Epilepsy
Temporal Lobe Epilepsy
Lead sponsor: University of Coimbra
Sponsor class: OTHER
First posted: 2025-01-23
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: This study aims to investigate the effect of lovastatin on neurotransmission and neuroinflammation in patients with temporal lobe onset drug resistant epilepsy.

Structure: (1) Visit 1: 3 consecutive days of physiologically probing drug/placebo intake, (2) Visit 2: Outcome measures and additional evaluations in the day after the last drug/placebo intake, (3) Washout period of 4 weeks, (4) 3 consecutive days of drug/placebo intake, (5) Visit 3: Outcome measures and additional evaluations in the day after the last placebo/drug intake.

Detailed description: This study investigates the potential therapeutic effects of lovastatin, a drug known for its anti-inflammatory and neuroprotective properties, in patients with temporal lobe drug-resistant epilepsy (DRE). Emerging evidence suggests that inflammation plays a significant role in epileptogenesis, and preclinical models of epilepsy have demonstrated the efficacy of statins in reducing seizure susceptibility.

This pilot, double-blinded, placebo-controlled crossover study included five participants with focal-onset DRE. The primary objectives were to evaluate the impact of lovastatin on cortical inhibition, oxidative stress, and seizure activity. Participants received 60 mg/day of lovastatin or placebo for a specified period, with treatment phases separated by a washout period.

Key assessments included magnetic resonance spectroscopy (MRS) to measure brain metabolites such as GABA, glutamate, and glutathione in the occipital cortex. Event-related potentials (ERP) were recorded during a facial recognition task to examine visual evoked potentials, while resting EEG was used to analyze interictal epileptiform discharges (IEDs).

Eligibility criteria: Inclusion Criteria:

* diagnosis of pharmacoresistant epilepsy as defined by the International League Against Epilepsy,
* focal temporal lobe onset
* nonpregnant and nonlactating in women

Exclusion Criteria:

* history of cardiovascular or cerebrovascular disease,
* history of dyslipidemia, previous use of statins or a previously documented adverse reaction to statins,
* having any metal inside the head but outside the mouth,
* implanted devices such as cardiac pacemakers or cochlear implants,
* having a vagal nerve stimulation device and the presence of other comorbid neurologic conditions

Primary outcomes:
measure: Neurochemical response changes to GABAergic stimulation
timeFrame: First day after placebo and first day after lovastatin intervention.
measure: Evaluation of neuroinflammation by measuring Glutathione as a marker of oxidative stress
timeFrame: First day after placebo and first day after lovastatin intervention.
Secondary outcomes:
Other outcomes:
Locations:
city: Coimbra
country: Portugal
facility: Institute of Nuclear Sciences Applied to Health
Study officials:
References: