The GABAergic Inhibitory System in Drug Resistant Epilepsy

Lovastatin Modulation of the Inhibition-excitation Balance in Temporal Lobe Onset Drug Resistant Epilepsy

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.

Study Overview

• Status: Completed
• Conditions: Drug Resistant Epilepsy; Temporal Lobe Epilepsy
• Intervention / Treatment: Drug: Lovastatin 60 MG; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 5
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Portugal
  • Coimbra, Portugal, 3000-548
    • Institute of Nuclear Sciences Applied to Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Participants were given placebo 60 mg/day for three consecutive days.
Experimental: Lovastatin	Drug: Lovastatin 60 MG; Participants were given lovastatin 60 mg/day for three consecutive days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	First day after placebo and first day after lovastatin intervention.
Evaluation of neuroinflammation by measuring Glutathione as a marker of oxidative stress		First day after placebo and first day after lovastatin intervention.

Collaborators and Investigators

• Sponsor: University of Coimbra

Study record dates

Study Major Dates

• Study Start (Actual): January 12, 2020
• Primary Completion (Actual): January 1, 2024
• Study Completion (Actual): April 1, 2024

Study Registration Dates

• First Submitted: January 17, 2025
• First Submitted That Met QC Criteria: January 17, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 17, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Epileptic Syndromes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsies, Partial; Drug Resistant Epilepsy; Epilepsy; Epilepsy, Temporal Lobe; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lovastatin; L 647318; Dihydromevinolin
• Other Study ID Numbers: CIBIT-EPILEPSY-1; FLAD Life Science 2020 (Other Grant/Funding Number: Luso-American Development Foundation)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No