EpilepsyNCT04716673
Stimulation of Sleep in Patients With Epilepsy
A study testing Down-phase targeted auditory stimulation in people with Epilepsy, run by University Children's Hospital, Zurich at 1 site in Switzerland.
Trial summary
Sleep slow waves (SSW) and the pathophysiological mechanisms of spike generation in patients with epilepsy are tightly linked. SSW are cortically generated oscillations (~1 Hz) alternating between a hyperpolarized down-state (neuronal silence) and a depolarized up-state (neuronal firing). Read more about this study
- Who is it for?
- Ages 4 to 30 yearsHealthy volunteers can take part
- Conditions the study is for
- Epilepsy
- What is being tested?
- Down-phase targeted auditory stimulation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteSwitzerland
- Study dates
- 29 Jul 2020to Dec 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 30 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- Participants of any gender
- Children, adolescents and young adults (4-30 years old)
- Right-handed
- Written informed consent by the participant or, if applicable, by their legal guardian after receiving information about the study For healthy participants:
- Good general health status
- For patients with epilepsy:
Show all 9Show fewer
- Diagnosed with epilepsy
- Wake or sleep EEG within the last 12 months showing epileptic discharges.
- Attending a regular school.
Who cannot join
- Irregular sleep-wake rhythm
- Shift work
- Daytime sleep
- Excessive sweating
- Obesity
- Sleep, psychiatric, neurological or physical disorders or illnesses other than epilepsy
Show all 26Show fewer
- Hearing disorder
- Travelling across 2 or more time zones within the last month
- Pregnancy
- Skin allergy or very sensitive skin
- Drug and medication use or abuse other than for the treatment of epilepsy
- Daily nicotine use
- High caffeine consumption, including coffee, black and green tea, mate, cola, energy drinks, and iced tea
- <16 years: >1 servings/day = >80 mg caffeine
- >=16 years: >2 servings/day = >160 mg caffeine
- Alcohol consumption
- <16 years: any alcohol
- 16-17 years: >3-4 standard servings per week
- >=18 years: >1 standard serving per day (>14 mg)
- Inability to follow the procedures of the study For patients with epilepsy:
- Epilepsy syndromes with a high risk of seizure occurrence during the study night
- Generalized motor and/or focal motor seizure frequency >1/week
- Generalized motor and/or focal motor seizure within 24h before the study night
- History of convulsive status epilepticus
- History of seizures provoked by sleep deprivation
- Treatment with corticosteroids, immunosuppressants or vagus nerve stimulation
Trial locations and contacts
1 site in 1 country.
Switzerland1 site, 1 recruiting
- Recruiting
University Children's Hospital Zurich
Zurich, 8032
Sven Leach, M. Sc., +41 44 266 3217, sven.leach@kispi.uzh.ch
Reto Huber, Prof. Dr.
About this study
Official title: Investigating the Effect of Closed-loop Auditory Stimulation on Sleep and Behavior in Patients With Epilepsy and Healthy Controls: a Developmental Study
Sleep slow waves (SSW) and the pathophysiological mechanisms of spike generation in patients with epilepsy are tightly linked. SSW are cortically generated oscillations (~1 Hz) alternating between a hyperpolarized down-state (neuronal silence) and a depolarized up-state (neuronal firing). It has been shown experimentally that with increasing synchrony of slow neuronal oscillations, spike wave occurrence is facilitated. Auditory stimulation applied in correspondence to the SSW "up-phase" may increase the amplitude of the following SSW. Contrarywise, tones applied at the SSW "down-phase" may have a disruptive effect on SSW.
Participants: Patients with epilepsy with epileptic discharges in their sleep EEG, as well as healthy controls
Objective: Characterizing the effects of down-phase-targeted auditory stimulation on behavior and sleep EEG characteristics and determine whether the changes in sleep EEG characteristics are associated with the changes in behavior and wake EEG characteristics.
Read the detailed description
The investigators aim to evaluate the effect of closed-loop auditory stimulation during sleep in healthy children, adolescents and adults, as well children, adolescents and adults with epilepsy. During closed-loop auditory stimulation, a brief, quiet, non-arousing auditory stimuli, e.g. brief bursts of pink noise (50ms), are presented at specific moments during sleep. This procedure allows to noninvasively interact with endogenous brain activity and to influence sleep-dependent neuroplasticity.
Sleep slow waves (SSW) and the pathophysiological mechanisms of spike generation in patients with epilepsy are tightly linked. SSW are cortically generated oscillations (~1 Hz) alternating between a hyperpolarized down-state (neuronal silence) and a depolarized up-state (neuronal firing). It has been shown experimentally that with increasing synchrony of slow neuronal oscillations, spike wave occurrence is facilitated. Auditory stimulation applied in correspondence to the SSW "up-phase" may increase the amplitude of the following SSW. Contrarywise, tones applied at the SSW "down-phase" may have a disruptive effect on SSW.
In a control week participants' usual sleeping behavior will be assessed using activity meters and sleep diaries. During the lab visits, sleep and wake brain activity will be measured using EEG at the sleep laboratory. For sleep recordings, other standard polysomnographic (PSG) measures will be recorded as well. Within the study, further measures include a structural MRI, IQ, as well as motor, cognitive, and vigilance tests. Participants' well-being and tolerance to the intervention will be assessed with questionnaires.
Thus, the investigators will have the following source data: PSG data, computer based test results (cognitive functioning, vigilance, memory and motor tests), IQ and questionnaire data, actigraphy data, and, depending on the participant and the availability of the MRI scanner, structural MRI data.
The sample size of the study is based on previous publications showing a significant effect of closed-loop auditory stimulation on NREM sleep EEG markers and declarative memory consolidation (Ngo et al., 2013). By including 11 participants they could demonstrate significant results both for the behavioral and electrophysiological data. Therefore, the investigators assume that it would be statistically meaningful to recruit at least 20 subjects per age group.
As the goal is to record 160 complete datasets, all these datasets will be used for the analysis. Incomplete datasets due to early withdrawal can be included partially for analyses in which only the available measures are included.
For any given analysis, datasets missing the relevant data will be excluded. The investigators will ensure that no analysis is based on less than 90% of the pursued sample size, meaning that at least 18 datasets per age and health group will enter all analyses (healthy participants or patients with epilepsy of a particular age group). In other words, no more than two participants would be excluded between outliers and missing data. Should this be exceeded, the investigators will compensate by recruiting additional participants
The data quality will be checked immediately after each experimental session to confirm the correct timing of presented sounds, as well as to assess the effect of closed-loop auditory stimulation on sleep EEG markers. The experiment will be continued if there will be a significant change in slow-wave activity in the first 10 participants (p < 0.05, paired-samples t-test) associated with closed-loop auditory stimulation application. The final analysis described in the section below will be performed after all the data is collected.
All study data will be archived at University Children's Hospital for a minimum of 10 years after study termination or premature termination of the clinical trial. The anonymized EEGs are stored on the server of the EEG division of the University Children's Hospital.
Data generation, transmission, archiving and analysis strictly follows the current Swiss legal requirements for data protection. Personal identifiable information will be handled with complete confidentiality and will only be accessible to authorized personnel who require such information to fulfill their duties within the scope of the research project. The documents of the telephone interview are kept enclosed. On the project specific documents, participants are only identified by a unique participant number. Participant IDs and corresponding names will be saved in an encrypted participant identification list, accessible only to the Principal Investigator and authorized members of the team.
The Sponsor-Investigator is implementing and maintaining quality assurance and quality control systems with written SOPs and Working Instructions to ensure that trials are conducted and data are generated, documented (record), and reported in compliance with the protocol, GCP, and applicable regulatory requirement(s). Monitoring and audits will be conducted during the course of the study for quality assurance purposes. The day-to-day management of the study will be coordinated through the selected PhD student supervised by the postdoctoral researcher.
The investigator will allow the persons being responsible for the audit or the inspection to have access to the source data/documents and to answer any questions arising. All involved parties will keep the patient data strictly confidential.
- Conditions
- Epilepsy
- Being tested
- Down-phase targeted auditory stimulation
- Keywords
- epilepsy, sleep, closed-loop auditory stimulation, epileptic discharges, spikes
- Medical subject headings
- Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Down-phase targeted auditory stimulationOther
The presentation of a soft, brief tone (50 ms of pink noise). The volume will be held low enough to avoid provoking arousals or awakenings. In case of a waking-up-reaction, the volume will be lowered in steps of 5 dB.
| Study group | Role | What they receive |
|---|---|---|
| Children (4-11y) with epilepsy | Experimental | Down-phase-targeted closed-loop auditory stimulation is administered in each arm. Receives: Other: Down-phase targeted auditory stimulation |
| Teenagers (12-17y) with epilepsy | Experimental | Not described Receives: Other: Down-phase targeted auditory stimulation |
| Young adults (18-30y) with epilepsy | Experimental | Not described Receives: Other: Down-phase targeted auditory stimulation |
| Healthy children (4-11y) | Experimental | Not described Receives: Other: Down-phase targeted auditory stimulation |
| Healthy teenagers (12-17y) | Experimental | Not described Receives: Other: Down-phase targeted auditory stimulation |
| Healthy young adults (18-30y) | Experimental | Not described Receives: Other: Down-phase targeted auditory stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
CLAS on EEG characteristics & behavior
CLAS changes sleep EEG characteristics (slow-wave and spindle activity) and the measured behavior (e.g. cognitive, memory and motor performance).
Measured: Up to 4 years
EEG characteristics on behavior & wake EEG characteristics
The changes in sleep EEG characteristics (slow-wave and spindle activity) correlate with the changes in measured behavior (attention [TAP battery], reaction time [TAP battery], and declarative [word-pair memory task] \& spatial memory [object-location task]) and wake EEG characteristics (frequencies up to 40 Hz).
Measured: Up to 4 years
Secondary outcomes (6)
Performance in attention in epilepsy patients
Attention (measured with TAP battery) of patients with epilepsy is restored to the level of healthy participants of the same age.
Measured: Up to 4 years
Performance in reaction times in epilepsy patients
Reaction times (measured with TAP battery) of patients with epilepsy is restored to the level of healthy participants of the same age.
Measured: Up to 4 years
Performance in spatial memory in epilepsy patients
Spatial memory (measured with object-location task) of patients with epilepsy is restored to the level of healthy participants of the same age.
Measured: Up to 4 years
Performance in declarative memory in epilepsy patients
Declarative memory (measured with word-pair memory task) of patients with epilepsy is restored to the level of healthy participants of the same age.
Measured: Up to 4 years
CLAS on sleep slow waves
Qualitative exploration of CLAS effect on the sleep slow waves across different age groups.
Measured: Up to 4 years
CLAS on other sleep EEG characteristics, such as sleep spindles
Qualitative exploration of CLAS effect on other sleep EEG characteristics, such as sleep spindles across different age groups.
Measured: Up to 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2021
- Study start29 Jul 2020
- Primary completionOct 2022 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (16)Papers the sponsor has linked to this study.
- Other trials for EpilepsyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- The investigators aim to evaluate the effect of closed-loop auditory stimulation during sleep in healthy children, adolescents and adults, as well children, adolescents and adults with epilepsy. During closed-loop auditory stimulation, a brief, quiet, non-arousing auditory stimuli, e.g. brief bursts of pink noise (50ms), are presented at specific moments during sleep (STIM condition). This procedure allows to noninvasively interact with endogenous brain activity and to influence sleep-dependent neuroplasticity. During one experimental night, closed-loop auditory stimulation will be applied (STIM night). In the SHAM night, the experimental set-up is the same as in the experimental night, but no sounds will be presented.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Children's Hospital, Zurich
- Sponsor type
- University, hospital or other
- Collaborators
- ETH Zurich, University of Zurich
- Responsible party
- Sponsor
- Investigators
- Reto Huber, Prof. Dr., Principal investigator, University Children's Hospital, Zurich
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04716673
- Sponsor's protocol ID
- 2019-02134
- Other IDs
- 2019
- Status last verified
- Jan 2021
- First submitted
- 14 Dec 2020
- Last updated
- 20 Jan 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Voluntary approval of the participant or legal guardian of the participant is given by signed informed consent. Personal data will be collected and immediately coded to provide strict confidentiality. The participant code will only be available to the principal investigator and research coordinators. The EEG data, completely anonymized, will be made publicly available to be used in other studies, for which the participant must provide separate consent. The investigators comply with all legal provisions of the Data Protection Act. The data, fully anonymized, will be published in a dedicated online repository. The data includes * PSG data + CLAS triggers * Basic demographic information: gender, age, socioeconomic status, handedness * Chronotype score * Responses to behavioral tests * Actigraphy * Sleep quality and sleepiness scores
Publications
Bellesi M, Riedner BA, Garcia-Molina GN, Cirelli C, Tononi G. Enhancement of sleep slow waves: underlying mechanisms and practical consequences. Front Syst Neurosci. 2014 Oct 28;8:208. doi: 10.3389/fnsys.2014.00208. eCollection 2014.
PubMed 25389394Bolsterli BK, Gardella E, Pavlidis E, Wehrle FM, Tassinari CA, Huber R, Rubboli G. Remission of encephalopathy with status epilepticus (ESES) during sleep renormalizes regulation of slow wave sleep. Epilepsia. 2017 Nov;58(11):1892-1901. doi: 10.1111/epi.13910. Epub 2017 Sep 27.
PubMed 28960278Bolsterli BK, Schmitt B, Bast T, Critelli H, Heinzle J, Jenni OG, Huber R. Impaired slow wave sleep downscaling in encephalopathy with status epilepticus during sleep (ESES). Clin Neurophysiol. 2011 Sep;122(9):1779-87. doi: 10.1016/j.clinph.2011.01.053. Epub 2011 Mar 26.
PubMed 21441067Bolsterli Heinzle BK, Fattinger S, Kurth S, Lebourgeois MK, Ringli M, Bast T, Critelli H, Schmitt B, Huber R. Spike wave location and density disturb sleep slow waves in patients with CSWS (continuous spike waves during sleep). Epilepsia. 2014 Apr;55(4):584-91. doi: 10.1111/epi.12576. Epub 2014 Mar 20.
PubMed 24650120Diekelmann S, Born J. The memory function of sleep. Nat Rev Neurosci. 2010 Feb;11(2):114-26. doi: 10.1038/nrn2762. Epub 2010 Jan 4.
PubMed 20046194Esser SK, Hill SL, Tononi G. Sleep homeostasis and cortical synchronization: I. Modeling the effects of synaptic strength on sleep slow waves. Sleep. 2007 Dec;30(12):1617-30. doi: 10.1093/sleep/30.12.1617.
PubMed 18246972Fattinger S, de Beukelaar TT, Ruddy KL, Volk C, Heyse NC, Herbst JA, Hahnloser RHR, Wenderoth N, Huber R. Deep sleep maintains learning efficiency of the human brain. Nat Commun. 2017 May 22;8:15405. doi: 10.1038/ncomms15405.
PubMed 28530229Fattinger S, Heinzle BB, Ramantani G, Abela L, Schmitt B, Huber R. Closed-Loop Acoustic Stimulation During Sleep in Children With Epilepsy: A Hypothesis-Driven Novel Approach to Interact With Spike-Wave Activity and Pilot Data Assessing Feasibility. Front Hum Neurosci. 2019 May 21;13:166. doi: 10.3389/fnhum.2019.00166. eCollection 2019.
PubMed 31164813Fattinger S, Schmitt B, Bolsterli Heinzle BK, Critelli H, Jenni OG, Huber R. Impaired slow wave sleep downscaling in patients with infantile spasms. Eur J Paediatr Neurol. 2015 Mar;19(2):134-42. doi: 10.1016/j.ejpn.2014.11.002. Epub 2014 Nov 29.
PubMed 25530030Frauscher B, von Ellenrieder N, Ferrari-Marinho T, Avoli M, Dubeau F, Gotman J. Facilitation of epileptic activity during sleep is mediated by high amplitude slow waves. Brain. 2015 Jun;138(Pt 6):1629-41. doi: 10.1093/brain/awv073. Epub 2015 Mar 19.
PubMed 25792528Galer S, Urbain C, De Tiege X, Emeriau M, Leproult R, Deliens G, Nonclerq A, Peigneux P, Van Bogaert P. Impaired sleep-related consolidation of declarative memories in idiopathic focal epilepsies of childhood. Epilepsy Behav. 2015 Feb;43:16-23. doi: 10.1016/j.yebeh.2014.11.032. Epub 2014 Dec 26.
PubMed 25546732Halasz P, Bodizs R, Ujma PP, Fabo D, Szucs A. Strong relationship between NREM sleep, epilepsy and plastic functions - A conceptual review on the neurophysiology background. Epilepsy Res. 2019 Feb;150:95-105. doi: 10.1016/j.eplepsyres.2018.11.008. Epub 2019 Jan 31.
PubMed 30712997Huber R, Ghilardi MF, Massimini M, Tononi G. Local sleep and learning. Nature. 2004 Jul 1;430(6995):78-81. doi: 10.1038/nature02663. Epub 2004 Jun 6.
PubMed 15184907Ngo HV, Martinetz T, Born J, Molle M. Auditory closed-loop stimulation of the sleep slow oscillation enhances memory. Neuron. 2013 May 8;78(3):545-53. doi: 10.1016/j.neuron.2013.03.006. Epub 2013 Apr 11.
PubMed 23583623Vyazovskiy VV, Harris KD. Sleep and the single neuron: the role of global slow oscillations in individual cell rest. Nat Rev Neurosci. 2013 Jun;14(6):443-51. doi: 10.1038/nrn3494. Epub 2013 May 2.
PubMed 23635871
Study at a glance
From the registry record, last updated by the sponsor on 20 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigating the Effect of Closed-loop Auditory Stimulation on Sleep and Behavior in Patients With Epilepsy and Healthy Controls: a Developmental Study
- ClinicalTrials.gov ID
- NCT04716673
- Acronym / sponsor ID
- 2019-02134
- Conditions
- Epilepsy
- Keywords
- epilepsy, sleep, closed-loop auditory stimulation, epileptic discharges, spikes
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- University Children's Hospital, ZurichUniversity, hospital or other
- Collaborators
- ETH Zurich, University of Zurich
- Study start
- 29 Jul 2020 (actual)
- Primary completion
- Oct 2022 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 20 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Sleep slow waves (SSW) and the pathophysiological mechanisms of spike generation in patients with epilepsy are tightly linked. SSW are cortically generated oscillations (~1 Hz) alternating between a hyperpolarized down-state (neuronal silence) and a depolarized up-state (neuronal firing). It has been shown experimentally that with increasing synchrony of slow neuronal oscillations, spike wave occurrence is facilitated. Auditory stimulation applied in correspondence to the SSW "up-phase" may increase the amplitude of the following SSW. Contrarywise, tones applied at the SSW "down-phase" may have a disruptive effect on SSW.
Participants: Patients with epilepsy with epileptic discharges in their sleep EEG, as well as healthy controls
Objective: Characterizing the effects of down-phase-targeted auditory stimulation on behavior and sleep EEG characteristics and determine whether the changes in sleep EEG characteristics are associated with the changes in behavior and wake EEG characteristics.
Detailed description
The investigators aim to evaluate the effect of closed-loop auditory stimulation during sleep in healthy children, adolescents and adults, as well children, adolescents and adults with epilepsy. During closed-loop auditory stimulation, a brief, quiet, non-arousing auditory stimuli, e.g. brief bursts of pink noise (50ms), are presented at specific moments during sleep. This procedure allows to noninvasively interact with endogenous brain activity and to influence sleep-dependent neuroplasticity.
Sleep slow waves (SSW) and the pathophysiological mechanisms of spike generation in patients with epilepsy are tightly linked. SSW are cortically generated oscillations (~1 Hz) alternating between a hyperpolarized down-state (neuronal silence) and a depolarized up-state (neuronal firing). It has been shown experimentally that with increasing synchrony of slow neuronal oscillations, spike wave occurrence is facilitated. Auditory stimulation applied in correspondence to the SSW "up-phase" may increase the amplitude of the following SSW. Contrarywise, tones applied at the SSW "down-phase" may have a disruptive effect on SSW.
In a control week participants' usual sleeping behavior will be assessed using activity meters and sleep diaries. During the lab visits, sleep and wake brain activity will be measured using EEG at the sleep laboratory. For sleep recordings, other standard polysomnographic (PSG) measures will be recorded as well. Within the study, further measures include a structural MRI, IQ, as well as motor, cognitive, and vigilance tests. Participants' well-being and tolerance to the intervention will be assessed with questionnaires.
Thus, the investigators will have the following source data: PSG data, computer based test results (cognitive functioning, vigilance, memory and motor tests), IQ and questionnaire data, actigraphy data, and, depending on the participant and the availability of the MRI scanner, structural MRI data.
The sample size of the study is based on previous publications showing a significant effect of closed-loop auditory stimulation on NREM sleep EEG markers and declarative memory consolidation (Ngo et al., 2013). By including 11 participants they could demonstrate significant results both for the behavioral and electrophysiological data. Therefore, the investigators assume that it would be statistically meaningful to recruit at least 20 subjects per age group.
As the goal is to record 160 complete datasets, all these datasets will be used for the analysis. Incomplete datasets due to early withdrawal can be included partially for analyses in which only the available measures are included.
For any given analysis, datasets missing the relevant data will be excluded. The investigators will ensure that no analysis is based on less than 90% of the pursued sample size, meaning that at least 18 datasets per age and health group will enter all analyses (healthy participants or patients with epilepsy of a particular age group). In other words, no more than two participants would be excluded between outliers and missing data. Should this be exceeded, the investigators will compensate by recruiting additional participants
The data quality will be checked immediately after each experimental session to confirm the correct timing of presented sounds, as well as to assess the effect of closed-loop auditory stimulation on sleep EEG markers. The experiment will be continued if there will be a significant change in slow-wave activity in the first 10 participants (p < 0.05, paired-samples t-test) associated with closed-loop auditory stimulation application. The final analysis described in the section below will be performed after all the data is collected.
All study data will be archived at University Children's Hospital for a minimum of 10 years after study termination or premature termination of the clinical trial. The anonymized EEGs are stored on the server of the EEG division of the University Children's Hospital.
Data generation, transmission, archiving and analysis strictly follows the current Swiss legal requirements for data protection. Personal identifiable information will be handled with complete confidentiality and will only be accessible to authorized personnel who require such information to fulfill their duties within the scope of the research project. The documents of the telephone interview are kept enclosed. On the project specific documents, participants are only identified by a unique participant number. Participant IDs and corresponding names will be saved in an encrypted participant identification list, accessible only to the Principal Investigator and authorized members of the team.
The Sponsor-Investigator is implementing and maintaining quality assurance and quality control systems with written SOPs and Working Instructions to ensure that trials are conducted and data are generated, documented (record), and reported in compliance with the protocol, GCP, and applicable regulatory requirement(s). Monitoring and audits will be conducted during the course of the study for quality assurance purposes. The day-to-day management of the study will be coordinated through the selected PhD student supervised by the postdoctoral researcher.
The investigator will allow the persons being responsible for the audit or the inspection to have access to the source data/documents and to answer any questions arising. All involved parties will keep the patient data strictly confidential.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 6
- Model description
- The investigators aim to evaluate the effect of closed-loop auditory stimulation during sleep in healthy children, adolescents and adults, as well children, adolescents and adults with epilepsy. During closed-loop auditory stimulation, a brief, quiet, non-arousing auditory stimuli, e.g. brief bursts of pink noise (50ms), are presented at specific moments during sleep (STIM condition). This procedure allows to noninvasively interact with endogenous brain activity and to influence sleep-dependent neuroplasticity. During one experimental night, closed-loop auditory stimulation will be applied (STIM night). In the SHAM night, the experimental set-up is the same as in the experimental night, but no sounds will be presented.
| Arm | Type | Receives |
|---|---|---|
| Children (4-11y) with epilepsy | Experimental | Other: Down-phase targeted auditory stimulationDown-phase-targeted closed-loop auditory stimulation is administered in each arm. |
| Teenagers (12-17y) with epilepsy | Experimental | Other: Down-phase targeted auditory stimulation |
| Young adults (18-30y) with epilepsy | Experimental | Other: Down-phase targeted auditory stimulation |
| Healthy children (4-11y) | Experimental | Other: Down-phase targeted auditory stimulation |
| Healthy teenagers (12-17y) | Experimental | Other: Down-phase targeted auditory stimulation |
| Healthy young adults (18-30y) | Experimental | Other: Down-phase targeted auditory stimulation |
Who may qualify
- Ages
- 4 to 30 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (9 listed)
- Participants of any gender
- Children, adolescents and young adults (4-30 years old)
- Right-handed
- Written informed consent by the participant or, if applicable, by their legal guardian after receiving information about the study For healthy participants:
- Good general health status
Key exclusion criteria (26 listed)
- Irregular sleep-wake rhythm
- Shift work
- Daytime sleep
- Excessive sweating
- Obesity
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Down-phase targeted auditory stimulationThe presentation of a soft, brief tone (50 ms of pink noise). The volume will be held low enough to avoid provoking arousals or awakenings. In case of a waking-up-reaction, the volume will be lowered in steps of 5 dB. | Other | Children (4-11y) with epilepsy, Healthy children (4-11y), Healthy teenagers (12-17y), Healthy young adults (18-30y), Teenagers (12-17y) with epilepsy, Young adults (18-30y) with epilepsy |
Primary outcome
CLAS on EEG characteristics & behavior
Time frame: Up to 4 years
CLAS changes sleep EEG characteristics (slow-wave and spindle activity) and the measured behavior (e.g. cognitive, memory and motor performance).
EEG characteristics on behavior & wake EEG characteristics
Time frame: Up to 4 years
The changes in sleep EEG characteristics (slow-wave and spindle activity) correlate with the changes in measured behavior (attention [TAP battery], reaction time [TAP battery], and declarative [word-pair memory task] \& spatial memory [object-location task]) and wake EEG characteristics (frequencies up to 40 Hz).
6 secondary outcomes
Performance in attention in epilepsy patients
Time frame: Up to 4 years
Performance in reaction times in epilepsy patients
Time frame: Up to 4 years
Performance in spatial memory in epilepsy patients
Time frame: Up to 4 years
Performance in declarative memory in epilepsy patients
Time frame: Up to 4 years
CLAS on sleep slow waves
Time frame: Up to 4 years
CLAS on other sleep EEG characteristics, such as sleep spindles
Time frame: Up to 4 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jan 2021.
- Background: PubMed 25389394Bellesi M, Riedner BA, Garcia-Molina GN, Cirelli C, Tononi G. Enhancement of sleep slow waves: underlying mechanisms and practical consequences. Front Syst Neurosci. 2014 Oct 28;8:208. doi: 10.3389/fnsys.2014.00208. eCollection 2014.
- Background: PubMed 28960278Bolsterli BK, Gardella E, Pavlidis E, Wehrle FM, Tassinari CA, Huber R, Rubboli G. Remission of encephalopathy with status epilepticus (ESES) during sleep renormalizes regulation of slow wave sleep. Epilepsia. 2017 Nov;58(11):1892-1901. doi: 10.1111/epi.13910. Epub 2017 Sep 27.
- Background: PubMed 21441067Bolsterli BK, Schmitt B, Bast T, Critelli H, Heinzle J, Jenni OG, Huber R. Impaired slow wave sleep downscaling in encephalopathy with status epilepticus during sleep (ESES). Clin Neurophysiol. 2011 Sep;122(9):1779-87. doi: 10.1016/j.clinph.2011.01.053. Epub 2011 Mar 26.
- Background: PubMed 24650120Bolsterli Heinzle BK, Fattinger S, Kurth S, Lebourgeois MK, Ringli M, Bast T, Critelli H, Schmitt B, Huber R. Spike wave location and density disturb sleep slow waves in patients with CSWS (continuous spike waves during sleep). Epilepsia. 2014 Apr;55(4):584-91. doi: 10.1111/epi.12576. Epub 2014 Mar 20.
- Background: PubMed 20046194Diekelmann S, Born J. The memory function of sleep. Nat Rev Neurosci. 2010 Feb;11(2):114-26. doi: 10.1038/nrn2762. Epub 2010 Jan 4.
- Background: PubMed 18246972Esser SK, Hill SL, Tononi G. Sleep homeostasis and cortical synchronization: I. Modeling the effects of synaptic strength on sleep slow waves. Sleep. 2007 Dec;30(12):1617-30. doi: 10.1093/sleep/30.12.1617.
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- Individual participant dataSharing planned: Yes. Voluntary approval of the participant or legal guardian of the participant is given by signed informed consent. Personal data will be collected and immediately coded to provide strict confidentiality. The participant code will only be available to the principal investigator and research coordinators. The EEG data, completely anonymized, will be made publicly available to be used in other studies, for which the participant must provide separate consent. The investigators comply with all legal provisions of the Data Protection Act. The data, fully anonymized, will be published in a dedicated online repository. The data includes * PSG data + CLAS triggers * Basic demographic information: gender, age, socioeconomic status, handedness * Chronotype score * Responses to behavioral tests * Actigraphy * Sleep quality and sleepiness scores
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Reto Huber, Prof. Dr. principal investigator
University Children's Hospital, Zurich
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Down-phase targeted auditory stimulation in people with Epilepsy, run by University Children's Hospital, Zurich at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 20 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Sven Leach, M. Sc. (+41 44 266 3217, sven.leach@kispi.uzh.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CLAS on EEG characteristics & behavior (time frame: Up to 4 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04716673, which also lists 16 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jan 2021.