Melatonin Versus Placebo in the Lennox-Gastaut Syndrome: Neurophysiological and Neuropsychological Effects

Double Blind, Randomised, Cross-over Study Melatonin Versus Placebo in the Lennox-Gastaut Syndrome: Neurophysiological and Neuropsychological Effects

Lennox-Gastaut syndrome is a severe epileptic encephalopathy of childhood. In that syndrome, various type of seizure occur, mainly tonic seizures, atonic seizures and atypical absences. The tonic seizure occur mostly at night.

The hypothesis is that the melatonin could have a positive effect in that syndrome, by reducing the epileptic activity (assessed in the polysomnographic record by counting the number of interictal and ictal discharges) and stabilizing the structure of sleep.

The study is double blind, randomised, cross-over designed.

Study Overview

• Status: Withdrawn
• Conditions: Lennox-Gastaut Syndrome
• Intervention / Treatment: Drug: melatonin; Drug: placebo

Detailed Description

The aim of the trial is to study the efficacity of melatonin in the Lennox-Gastaut syndrome, by assessing the reduction of the seizure/interictal discharges in polysomnography and assessing the sleep structure.

After initial recruitment, the baseline visit includes a polysomnography. The patients will then be randomised in two groups: melatonin (1 cp containing melatonin 2 mg 1x/d 1h before sleep) vs placebo (1 cp 1x/d 1h before sleep). The treatment (melatonin or placebo) will be given for 1 month.

After 1 month, the treatment will be stopped and another polysomnography will be recorded.

The patients will take no treatment (wash-out period) for 15 days. The second treatment phase is cross-over: the group that had melatonin in the first phase will take placebo for one month, and the group that had placebo in the first treatment phase will take melatonin for one month. A last polysomnography will be recorded after the second treatment phase.

The other medications (antiepileptic drugs) taken by the patients before the trial will not be modified.

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• Switzerland
  • Vaud
    • Lavigny, Vaud, Switzerland, 1175
      • Institution de Lavigny

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Lennox-Gastaut syndrome (based on ILAE classification, 1989)
• light mental retardation (QI 50-69)
• french mother tongue
• having someone helping the patient (parent and/or referent educator)
• informed consent have been given by the patient / guardian
• absence of concomitant evolutive affection or associated sleep pathologies
• collaboration of the patient, ability to complete all aspects of the trial.

Exclusion Criteria:

• epileptic syndrome other than Lennox-Gastaut, other neurologic and/or psychiatric disease
• moderate to severe mental retardation (QI < 50)
• psychiatric disease that could interfere with the diagnostic procedure
• specific sleep disorder (anamnestic and diagnosed on the polygraphic record), for example: sleep apnea syndrome, narcolepsy, restless legs syndrome, periodic legs movements, etc...

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: placebo	Drug: placebo; placebo cp 1x/d for 1 month
ACTIVE_COMPARATOR: melatonin	Drug: melatonin; melatonin cp 2 mg 1x/d for 1 month; Other Names: brand name: circadin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
diminution of at least 50% of the nocturnal interictal discharges and tonic seizures with the melatonin treatment	The patients will have three polysomnographic recording: at the baseline, one month after initiating the treatment (melatonin or placebo) and one month after the cross-over phase. The number of tonic seizure and if interictal discharges will be assessed. The primary outcome measure is a diminution of > 50% of the seizures/interictal discharges with the melatonin treatment.	assessed after 1 month and 2.5 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
augmentation of at least 15% of the amount of deep slow sleep with the melatonin treatment	The structure of sleep will be measured with the polysomnography (at baseline, after 1 month and after 2.5 months. The outcome measure is an augmentation of at least 15% of the deep slow sleep.	assessed after 1 month and 2.5 months.

Collaborators and Investigators

• Sponsor: Institution de Lavigny
• Investigators: Principal Investigator: Giovanni B. Foletti, MD, MER, Institution de Lavigny

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (ANTICIPATED): January 1, 2012
• Study Completion (ANTICIPATED): January 1, 2012

Study Registration Dates

• First Submitted: June 8, 2011
• First Submitted That Met QC Criteria: June 9, 2011
• First Posted (ESTIMATE): June 10, 2011

Study Record Updates

• Last Update Posted (ACTUAL): July 14, 2022
• Last Update Submitted That Met QC Criteria: July 12, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Melatonin; Quality of sleep; Epileptic encephalopathy; Lennox-Gastaut syndrome; Tonic seizures; Interictal discharges
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epileptic Syndromes; Disease; Genetic Diseases, Inborn; Epilepsy; Syndrome; Lennox Gastaut Syndrome; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Protective Agents; Antioxidants; Melatonin
• Other Study ID Numbers: 25/10