The GABAergic Inhibitory System in Drug Resistant Epilepsy

University of Coimbra5 enrolled

Overview

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.

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

QUADRUPLE

Enrollment

Conditions

Drug Resistant Epilepsy Temporal Lobe Epilepsy

Interventions

Lovastatin 60 MGDRUG

Participants were given lovastatin 60 mg/day for three consecutive days.

PlaceboDRUG

Participants were given placebo 60 mg/day for three consecutive days.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (1)

Institute of Nuclear Sciences Applied to Health

Coimbra, Coimbra District, Portugal

Outcomes

Primary Outcomes

Neurochemical response changes to GABAergic stimulation

Comparing changes in brain excitation-inhibition measures (i.e., glutamate and GABA) when the GABAergic system is activated by oral dose of the Lovastatin 60mg during 3 days versus the placebo condition.

Time frame: First day after placebo and first day after lovastatin intervention.

Evaluation of neuroinflammation by measuring Glutathione as a marker of oxidative stress

Time frame: First day after placebo and first day after lovastatin intervention.

Data from ClinicalTrials.gov

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