The GABAergic Inhibitory System in Drug Resistant Epilepsy

Not Applicable

Completed

• Conditions: Drug Resistant Epilepsy; Temporal Lobe Epilepsy
• Interventions: Drug: Lovastatin 60 MG; Drug: Placebo

• Registration Number: NCT06789497
• Lead Sponsor: University of Coimbra

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).

Study Timeline

• Study Start: 2020-01-12
• Primary Completion: 2024-01-01
• Study Completion: 2024-04-01
• Status Verified: 2025-01
• Study First Submitted: 2025-01-17
• Study First Submitted QC: 2025-01-17
• Last Update Submitted: 2025-01-17
• Study First Posted: 2025-01-23
• Last Update Posted: 2025-01-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 5

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Lovastatin	Lovastatin 60 MG	-
Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
Neurochemical response changes to GABAergic stimulation	First day after placebo and first day after lovastatin intervention.	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.
Evaluation of neuroinflammation by measuring Glutathione as a marker of oxidative stress	First day after placebo and first day after lovastatin intervention.

Trial Locations

Locations (1)

Institute of Nuclear Sciences Applied to Health; 🇵🇹 Coimbra, Portugal