The GABAergic Inhibitory System in Drug Resistant Epilepsy

NCT ID: NCT06789497

Last Updated: 2025-01-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-12
• Study Completion Date: 2024-04-01

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).

Conditions

Drug Resistant Epilepsy; Temporal Lobe Epilepsy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

Lovastatin

Group Type: EXPERIMENTAL

Lovastatin 60 MG

Intervention Type: DRUG

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

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

Lovastatin 60 MG

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

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Coimbra

OTHER

Sponsor Role: lead

Responsible Party

Miguel Castelo-Branco

Prof Dr

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Institute of Nuclear Sciences Applied to Health

Coimbra, Coimbra District, Portugal

Countries

Portugal

Other Identifiers

FLAD Life Science 2020

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

CIBIT-EPILEPSY-1

Identifier Type: -

Identifier Source: org_study_id