search
Back to results

Melatonin vs Sleep Deprivation for Nap EEG

Primary Purpose

Epilepsy

Status
Active
Phase
Not Applicable
Locations
Italy
Study Type
Interventional
Intervention
Melatonin
Deprivation
Sponsored by
IRCCS National Neurological Institute "C. Mondino" Foundation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Epilepsy focused on measuring Oral melatonin, Sleep deprivation, Nap EEG recordings, Time to fall asleep

Eligibility Criteria

4 Years - 10 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria: pediatric patients with epilepsy aged between 4 and 10 years with normal psychomotor development and IQ> 70; stable seizure frequency in the 3 months preceding the enrollment ; stable anti-seizure medications in the 3 months preceding the enrollment; written informed consent from the legal representative. Exclusion Criteria: subjects diagnosed with obstructive sleep apnea or other sleep disorders; history of neurodevelopmental disorders; concomitant use of hypnotics, stimulants, systemic corticosteroids or other immunosuppressants; concomitant daily use of melatonin; any conditions which, in the investigator's judgment, would compromise the achievement of the study objectives; refusal to sign the informed consent from the legal representative.

Sites / Locations

  • Child and Adolescent Epileptology Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Deprivation group

Melatonin group

Arm Description

Sleep deprivation of 50% of physiological sleep

Melatonin oral solution 5 mg 30 minutes before EEG performing

Outcomes

Primary Outcome Measures

Time elapsed (in seconds) from the starting of the EEG and beginning of sleep stages at EEG recording with melatonin
Disappearance of the background rhythm of the alpha band on the posterior regions and appearance of the physiological hypnic figures, characteristics of the N1 phase of non-REM sleep
Time elapsed (in seconds) from the starting of the EEG and beginning of sleep stages at EEG recording with deprivation
Disappearance of the background rhythm of the alpha band on the posterior regions and appearance of the physiological hypnic figures, characteristics of the N1 phase of non-REM sleep

Secondary Outcome Measures

Frequency of epileptic anomalies
Anomalies which occurs through the use of special instrumentation (so-called "tip counter tool", an automatic tool for detecting epileptiform anomalies on the electroencephalographic trace
Clinically detectable seizures
Presence/absence ofseizures
Levels of 6-sulfatoxymelatonina
Determination of the levels of the primary metabolite of melatonin in saliva and urine, with a validated LC-MS method

Full Information

First Posted
November 25, 2022
Last Updated
December 14, 2022
Sponsor
IRCCS National Neurological Institute "C. Mondino" Foundation
search

1. Study Identification

Unique Protocol Identification Number
NCT05654415
Brief Title
Melatonin vs Sleep Deprivation for Nap EEG
Official Title
Efficacy of Melatony Versus Sleep Deprivation for EEG Recordings in Sleep: a Randomized Crossed-over Study in Pediatric Patients With Epilepsy
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 1, 2021 (Actual)
Primary Completion Date
December 31, 2022 (Anticipated)
Study Completion Date
December 31, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
IRCCS National Neurological Institute "C. Mondino" Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
In the pediatric population, electroencephalographic (EEG) recordings are frequently performed in sleep, as it reduces the amount of artifacts and might activate epileptiform discharges. To date, no agreed-upon guidelines are available for hypno-induction for EEG recordings . Among the strategies used, the most commonly used are sleep deprivation, either total or partial, and the use of melatonin, alone or in combination. The investigators proposed a study aiming at evaluating the efficacy of a melatonin-based solution for sleep induction during EEG video recording VS sleep deprivation. In a randomized, crossover study, 30 pediatric patients (aged 4-10 years) will be subjected to two EEG recordings: in one they will receive the melatonin solution (5 mg), in the other they undergo only partial sleep deprivation (about 50% of physiological sleep). The primary endpoint of the study is represented by the time to fall asleep, secondary objectives are represented by frequency of epileptiform discharges, presence/absence of epileptic seizures, In addition, the levels of 6-sulfatoxymelatonina, the primary metabolite of melatonin in saliva and urine, will be determined with a validated LC-MS method.
Detailed Description
Background: Electroencephalographic recording is essential in children with suspected or diagnosed epilepsy. Due to difficulties in obtaining a reliable EEG, in pediatric patients electroencephalographic recordings are often performed during sleep in order to reduce the number of artefacts connected to movements and to activate epileptic discharges. To date, there are no shared guidelines about hypno-induction. Most of hypnotic drugs such as benzodiazepines and barbiturates are known to alter EEG registration, by changing background activity or epileptiform activities. Clinicians often aim to induce sleep by total or partial sleep deprivation. A recent survey assessing strategies used by various centers in Italy highlights that there is a great heterogeneous approach to obtain hypno-induction. Among sleep-inductive interventions, the use of melatonin is the most common alone or in combination with sleep-deprivation. Melatonin is a hormone (N-acetylmethoxytryptamine), produced by the pineal gland, whose secretion is regulated by the suprachiasmatic nucleus of the hypothalamus and which is able to regulate circadian rhythms. An open-lable study evaluated the role of melatonin on the EEG recordings (artefacts, anomalies) and its efficacy in inducing sleep in 50 children with epilepsy or with neurodevelopmental disorders. This study demonstrates that melatonin is not more effective than sleep deprivation in hypno-induction, without modifying the EEG pattern. Furthermore, melatonin is equally efficient as partial sleep deprivation in inducing sleep and does not affect the occurrence of epileptic discharges in the EEG recording. Another recent study combined sleep deprivation and melatonin revealing the greater effectiveness of the combination of the two methods against the use of them individually. However, this study was not randomized. Moreover, there is no clear consensus about when and in which doses melatonin should be administrated in children: doses vary between different studies ranging from 2 to 20 mg. From these observations it is clear, therefore, that the role of melatonin is strategic in hypno-induction and no cases of toxicity or adverse effects in the short and long term deriving from the use of melatonin are known in the literature. The aim of this randomized study is to determine non-inferiority of melatonin 5 mg against sleep deprivation in inducing sleep in a cohort of children and adolescents with epilepsy and to determine if melatonin could affect the frequency of epileptic discharges or clinically detectable epileptic seizures during nap EEG recordings. Furthermore, the investigators try to indicate an adequate dose for melatonin for hypno-induction. Moreover, the levels of 6-sulfatoxymelatonina, the primary metabolite of melatonin in saliva and urine, will be determined with a validated LC-MS method to detect a possible correlation between sleep induction and melatonin metabolism. Each enrolled patient will be subjected to two nap EEG recordings receiving in one the melatonin-based solution under study at a dosage of 5 mg, in the other they will be subjected to sleep deprivation (defined as 50% of physiological sleep). The electroencephalographic recordings with video and polygraphy in siesta at the same time, will be performed at a time distance of 1-3 months. The study is open label and therefore no masking method is used. In order to minimize the bias deriving from the open label situation, the calculation of the time to fall asleep is based on objective EEG parameters (disappearance of the background rhythm of the alpha band on the posterior regions and appearance of the physiological hypnic figures, characteristics of the N1 phase of non-REM sleep), as well as the calculation of the frequency of epileptic anomalies which occurs through the use of special instrumentation (so-called "tip counter tool", an automatic tool for detecting epileptiform anomalies on the electroencephalographic trace ). In addition, the levels of 6-sulfatoxymelatonina, the primary metabolite of melatonin in saliva and urine, will be determined with a validated LC-MS method. Duration of the study: 52 weeks Duration of enrollment: 36 weeks

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Epilepsy
Keywords
Oral melatonin, Sleep deprivation, Nap EEG recordings, Time to fall asleep

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Model Description
The patients will be subjected to two EEG recordings: in one they will receive the melatonin solution (5 mg), in the 'other they will undergo only partial sleep deprivation (about 50% of physiological sleep).
Masking
None (Open Label)
Allocation
Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Deprivation group
Arm Type
Experimental
Arm Description
Sleep deprivation of 50% of physiological sleep
Arm Title
Melatonin group
Arm Type
Experimental
Arm Description
Melatonin oral solution 5 mg 30 minutes before EEG performing
Intervention Type
Other
Intervention Name(s)
Melatonin
Intervention Description
Each enrolled patient will be subjected to two nap EEG recordings receiving in one occasion the melatonin-based solution under study at a dosage of 5 mg
Intervention Type
Other
Intervention Name(s)
Deprivation
Intervention Description
Each enrolled patient will be subjected to two nap EEG recordings,in one they will be subjected to sleep deprivation
Primary Outcome Measure Information:
Title
Time elapsed (in seconds) from the starting of the EEG and beginning of sleep stages at EEG recording with melatonin
Description
Disappearance of the background rhythm of the alpha band on the posterior regions and appearance of the physiological hypnic figures, characteristics of the N1 phase of non-REM sleep
Time Frame
From 0 seconds to 1.5 hours
Title
Time elapsed (in seconds) from the starting of the EEG and beginning of sleep stages at EEG recording with deprivation
Description
Disappearance of the background rhythm of the alpha band on the posterior regions and appearance of the physiological hypnic figures, characteristics of the N1 phase of non-REM sleep
Time Frame
From 0 seconds to 1.5 hours
Secondary Outcome Measure Information:
Title
Frequency of epileptic anomalies
Description
Anomalies which occurs through the use of special instrumentation (so-called "tip counter tool", an automatic tool for detecting epileptiform anomalies on the electroencephalographic trace
Time Frame
From 0 seconds to 1.5 hours
Title
Clinically detectable seizures
Description
Presence/absence ofseizures
Time Frame
From 0 seconds to 1.5 hours
Title
Levels of 6-sulfatoxymelatonina
Description
Determination of the levels of the primary metabolite of melatonin in saliva and urine, with a validated LC-MS method
Time Frame
120 minutes after oral melatonin solution

10. Eligibility

Sex
All
Minimum Age & Unit of Time
4 Years
Maximum Age & Unit of Time
10 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: pediatric patients with epilepsy aged between 4 and 10 years with normal psychomotor development and IQ> 70; stable seizure frequency in the 3 months preceding the enrollment ; stable anti-seizure medications in the 3 months preceding the enrollment; written informed consent from the legal representative. Exclusion Criteria: subjects diagnosed with obstructive sleep apnea or other sleep disorders; history of neurodevelopmental disorders; concomitant use of hypnotics, stimulants, systemic corticosteroids or other immunosuppressants; concomitant daily use of melatonin; any conditions which, in the investigator's judgment, would compromise the achievement of the study objectives; refusal to sign the informed consent from the legal representative.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Valentina De Giorgis, MD
Organizational Affiliation
Child and Adolescent Epileptology Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Child and Adolescent Epileptology Center
City
Pavia
ZIP/Postal Code
27100
Country
Italy

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
30028504
Citation
Alix JJP, Kandler RH, Pang C, Stavroulakis T, Catania S. Sleep deprivation and melatonin for inducing sleep in paediatric electroencephalography: a prospective multicentre service evaluation. Dev Med Child Neurol. 2019 Feb;61(2):181-185. doi: 10.1111/dmcn.13973. Epub 2018 Jul 20.
Results Reference
background
PubMed Identifier
21086220
Citation
Eisermann M, Kaminska A, Berdougo B, Brunet ML. Melatonin: experience in its use for recording sleep EEG in children and review of the literature. Neuropediatrics. 2010 Aug;41(4):163-6. doi: 10.1055/s-0030-1267920. Epub 2010 Nov 17.
Results Reference
background
PubMed Identifier
30140986
Citation
Gasparini S, Sueri C, Ascoli M, Cianci V, Cavalli SM, Ferrigno G, Belcastro V, Aguglia U, Ferlazzo E; Epilepsy Study Group of the Italian Neurological Society. Need for a standardized technique of nap EEG recordings: results of a national online survey in Italy. Neurol Sci. 2018 Nov;39(11):1911-1915. doi: 10.1007/s10072-018-3525-9. Epub 2018 Aug 23.
Results Reference
background
PubMed Identifier
25453612
Citation
Gustafsson G, Brostrom A, Ulander M, Vrethem M, Svanborg E. Occurrence of epileptiform discharges and sleep during EEG recordings in children after melatonin intake versus sleep-deprivation. Clin Neurophysiol. 2015 Aug;126(8):1493-7. doi: 10.1016/j.clinph.2014.10.015. Epub 2014 Oct 18.
Results Reference
background
PubMed Identifier
25862116
Citation
Jain SV, Horn PS, Simakajornboon N, Beebe DW, Holland K, Byars AW, Glauser TA. Melatonin improves sleep in children with epilepsy: a randomized, double-blind, crossover study. Sleep Med. 2015 May;16(5):637-44. doi: 10.1016/j.sleep.2015.01.005. Epub 2015 Jan 21.
Results Reference
background
PubMed Identifier
15195324
Citation
Julious SA. Sample sizes for clinical trials with normal data. Stat Med. 2004 Jun 30;23(12):1921-86. doi: 10.1002/sim.1783.
Results Reference
background
PubMed Identifier
10641606
Citation
Liamsuwan S, Grattan-Smith P, Fagan E, Bleasel A, Antony J. The value of partial sleep deprivation as a routine measure in pediatric electroencephalography. J Child Neurol. 2000 Jan;15(1):26-9. doi: 10.1177/088307380001500106.
Results Reference
background
PubMed Identifier
22124712
Citation
Sander J, Shamdeen MG, Gottschling S, Gortner L, Graber S, Meyer S. Melatonin does not influence sleep deprivation electroencephalogram recordings in children. Eur J Pediatr. 2012 Apr;171(4):675-9. doi: 10.1007/s00431-011-1640-1. Epub 2011 Nov 29.
Results Reference
background
PubMed Identifier
15961864
Citation
Smith SJ. EEG in the diagnosis, classification, and management of patients with epilepsy. J Neurol Neurosurg Psychiatry. 2005 Jun;76 Suppl 2(Suppl 2):ii2-7. doi: 10.1136/jnnp.2005.069245. No abstract available.
Results Reference
background
PubMed Identifier
11275541
Citation
Wassmer E, Quinn E, Whitehouse W, Seri S. Melatonin as a sleep inductor for electroencephalogram recordings in children. Clin Neurophysiol. 2001 Apr;112(4):683-5. doi: 10.1016/s1388-2457(00)00554-x.
Results Reference
background
PubMed Identifier
11730146
Citation
Wassmer E, Carter PF, Quinn E, McLean N, Welsh G, Seri S, Whitehouse WP. Melatonin is useful for recording sleep EEGs: a prospective audit of outcome. Dev Med Child Neurol. 2001 Nov;43(11):735-8. doi: 10.1017/s0012162201001347.
Results Reference
background

Learn more about this trial

Melatonin vs Sleep Deprivation for Nap EEG

We'll reach out to this number within 24 hrs