Stimulation of Sleep in Patients With Epilepsy

NCT04716673 | Unknown DMC

• 1 other identifier: 2019-02134
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief 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). 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.

Conditions

Epilepsy

Keywords

epilepsy; sleep; closed-loop auditory stimulation; epileptic discharges; spikes

Outcome Measures

Primary Outcomes (2)

• 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).

  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).

  Up to 4 years

Secondary Outcomes (6)

• Performance in attention in epilepsy patients

  Up to 4 years

• Performance in reaction times in epilepsy patients

  Up to 4 years

• Performance in spatial memory in epilepsy patients

  Up to 4 years

• Performance in declarative memory in epilepsy patients

  Up to 4 years

• CLAS on sleep slow waves

  Up to 4 years

Study Arms (6)

Children (4-11y) with epilepsy

EXPERIMENTAL

Down-phase-targeted closed-loop auditory stimulation is administered in each arm.

Other: Down-phase targeted auditory stimulation

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

Interventions

Down-phase targeted auditory stimulation OTHER

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.

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

Eligibility Criteria

• Age: 4 Years - 30 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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:
• Diagnosed with epilepsy
• Wake or sleep EEG within the last 12 months showing epileptic discharges.
• Attending a regular school.

You may not qualify if:

• Irregular sleep-wake rhythm
• Shift work
• Daytime sleep
• Excessive sweating
• Obesity
• Sleep, psychiatric, neurological or physical disorders or illnesses other than epilepsy
• 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

Sponsors & Collaborators

• University Children's Hospital, Zurich: lead
• ETH Zurich: collaborator
• University of Zurich: collaborator

Study Sites (1)

University Children's Hospital Zurich

Zurich, 8032, Switzerland

RECRUITING

Related Publications (16)

• 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.

  PMID: 25389394 BACKGROUND

• Bolsterli 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.

  PMID: 28960278 BACKGROUND

• Bolsterli 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.

  PMID: 21441067 BACKGROUND

• Bolsterli 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.

  PMID: 24650120 BACKGROUND

• Diekelmann 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.

  PMID: 20046194 BACKGROUND

• Esser 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.

  PMID: 18246972 BACKGROUND

• Fattinger 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.

  PMID: 28530229 BACKGROUND

• Fattinger 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.

  PMID: 31164813 BACKGROUND

• Fattinger 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.

  PMID: 25530030 BACKGROUND

• Frauscher 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.

  PMID: 25792528 BACKGROUND

• Galer 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.

  PMID: 25546732 BACKGROUND

• Halasz 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.

  PMID: 30712997 BACKGROUND

• Huber 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.

  PMID: 15184907 BACKGROUND

• Ngo 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.

  PMID: 23583623 BACKGROUND

• Vyazovskiy 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.

  PMID: 23635871 BACKGROUND

• Vyazovskiy VV, Olcese U, Lazimy YM, Faraguna U, Esser SK, Williams JC, Cirelli C, Tononi G. Cortical firing and sleep homeostasis. Neuron. 2009 Sep 24;63(6):865-78. doi: 10.1016/j.neuron.2009.08.024.

  PMID: 19778514 BACKGROUND

MeSH Terms

Conditions

Epilepsy

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Reto Huber, Prof. Dr.

  University Children's Hospital, Zurich

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sven Leach, M. Sc.

CONTACT

+41 44 266 3217; sven.leach@kispi.uzh.ch

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Study helpers
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: December 14, 2020
• First Posted: January 20, 2021
• Study Start: July 29, 2020
• Primary Completion: October 1, 2022
• Study Completion: December 1, 2025
• Last Updated: January 20, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will share
• Time Frame: Start: December 2019 End: December 2025
• Access Criteria: Ideally, the investigators would like to publish the data through the University of Zurich, which is currently in the process of developing and contributing to the SWISSUbase. Unfortunately, at this time, the repository for neural, biological or psychology data has not yet been created. If, by the time of publication, this is still unavailable, the investigators will choose a repository that is compliant with the FAIR principles such as OpenNeuro. At the end of the project the investigators will evaluate the infrastructures available; it is conceivable that a Swiss university resource, or more suitable repository, will be established by then.

Locations

CH (1)