Effect of Auditory Stimulation on Spike Waves in Sleep (ECLASS)

Effect of Closed-loop Auditory Stimulation on Spike Waves During Slow Wave Sleep, an Open Label Pilot Study

Background: Close relationship exists between sleep slow wave (SSW) and the generation of spike wave in NREM-sleep. SSW are cortically generated oscillations alternating between excitatory depolarization ("Up-phase" of the SSW) and inhibitory hyperpolarization ("Down-phase" of the SSW). It has been shown experimentally that with increasing synchrony of slow neuronal oscillations SSW turn into spike waves. Acoustic pulses applied in correspondence to the SSW "Up-phase" enhance the amplitude of the subsequent SSW. Conversely, tones delivered at the SSW "Downphase" have a disruptive effect on the following SSW.

Participants: Patients with epilepsy and spike waves in NREM-sleep.

Objective: Modification of spike wave frequency, amplitude and spreading during NREM sleep by acoustic pulses applied at the "Up-" or "Down-phase" of SSW.

Study Overview

• Status: Completed
• Conditions: Epilepsy; Sleep
• Intervention / Treatment: Device: Acoustic pulses

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Zurich, Switzerland, CH-8032
    • Div. of Clinical Neurophysiology/Epilepsy, University Children's Hospital Zurich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participants with Rolandic epilepsy/BECTS
• Participants with ESES/CSWS
• Participants with generalized spike waves in sleep
• EEG within 6 months before study night consistent with the diagnosis

Exclusion Criteria:

• Clinically significant concomitant acute or chronic disease
• Seizure frequency >1/week, history of convulsive status epilepticus or seizures provoked by sleep deprivation
• Severe sleep problems
• Treatment with corticosteroids, immunosuppressive or vagus nerve stimulation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Acoustic pulses; During NREM sleep: 15 minutes without acoustic pulses; 15 minutes with acoustic pulses; 15 minutes without acoustic pulses Two different protocols are applied: (A) tone application at the "Down-phase" of sleep slow wave (SSW) (B) tone application at the "Up-phase" of SSW. Participants with Rolandic epilepsy/BECTS or generalized spike waves: Protocol A and B alternatingly. Participants with ESES/CSWS: only Protocol A.

Device: Acoustic pulses; Acoustic pulses applied during NREM sleep slow waves "Up-phase" or "Down-phase". The acoustic stimulus will be delivered by speakers with a volume of about 50 dB.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Spike wave index	Change of spike wave index during acoustic pulses applied at the "Up-" or "Down-phase" of sleep slow waves. Spike wave index given in percent and calculated by number of seconds within 10 second windows with spike waves over the whole 15 minutes of the block design part.	Change baseline (without) and with acoustic pulses in the same NREM period: 45 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Spike wave amplitude	Change of spike wave amplitude (in microvolts) during acoustic pulses applied at the "Up-" or "Down-phase" of sleep slow waves. Amplitudes of maximum spike will be analyzed in 10 seconds periods of the first and the last 100 seconds of every part of the block design. EEG source derivation will be used for the analysis. The mean of the 3 highest amplitudes of each 10 seconds period will be determined and the mean of the 10 periods will presented in mean and SD.	Change baseline (without) and with acoustic pulses in the same NREM period: 45 minutes
Spike wave spreading	Change of spike wave spreading during acoustic pulses applied at the "Up-" or "Down-phase" of sleep slow waves. Spreading will be analyzed in 10 seconds periods of the first and the last 100 seconds of every part of the block design. EEG source derivation will be used for the analysis. Maximum spike wave spreading (number of electrodes involved) visible in 3 spike waves of each 10 second period will be determined and the mean of the 10 periods will presented in mean and SD.	Change baseline (without) and with acoustic pulses in the same NREM period: 45 minutes
Spike wave index in the NREM (2) period following the NREM (1) period with acoustic pulses	Change of spike wave index in the NREM period following the NREM period with acoustic pulses applied at the "Up-" or "Down-phase" of sleep slow waves. Over the first 15 minutes of the following NREM period: Spike wave index given in percent and calculated by number of seconds within 10 second windows with spike waves .	Change baseline (NREM 1) and NREM 2: expected average of 1 hour
Spike wave amplitude in the NREM (2) period following the NREM (1) period with acoustic pulses	Change of spike wave amplitude (in microvolts) in the NREM period following the NREM period with acoustic pulses applied at the "Up-" or "Down-phase" of sleep slow waves. Amplitudes of maximum spike will be analyzed in 10 seconds periods of the first and the last 100 seconds of the following NREM period. EEG source derivation will be used for the analysis. The mean of the 3 highest amplitudes of each 10 seconds period will be determined and the mean of the 10 periods will presented in mean and SD.	Change baseline (NREM 1) and NREM 2: expected average of 1 hour
Spike wave spreading in the NREM (2) period following the NREM (1) period with acoustic pulses	Change of spike wave spreading in the NREM period following the NREM period with acoustic pulses applied at the "Up-" or "Down-phase" of sleep slow waves. Spreading will be analyzed in 10 seconds periods of the first and the last 100 seconds of the following NREM period. EEG source derivation will be used for the analysis. Maximum spike wave spreading (number of electrodes involved) visible in 3 spike waves of each 10 second period will be determined and the mean of the 10 periods will presented in mean and SD.	Change baseline (NREM 1) and NREM 2: expected average of 1 hour

Collaborators and Investigators

• Sponsor: University Children's Hospital, Zurich
• Investigators: Principal Investigator: Bernhard Schmitt, MD, Div. of Clinical Neurophysiology/Epilepsy, University Children's Hospital, Steinwiesstrasse 75, CH-8032 Zurich

Study record dates

Study Major Dates

• Study Start: October 1, 2015
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: September 21, 2015
• First Submitted That Met QC Criteria: September 25, 2015
• First Posted (Estimate): September 29, 2015

Study Record Updates

• Last Update Posted (Estimate): January 13, 2017
• Last Update Submitted That Met QC Criteria: January 12, 2017
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: Electroencephalography; Benign epilepsy with centro-temporal spikes; Continuous spike waves in slow wave sleep; Sleep, slow wave
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy
• Other Study ID Numbers: SW2015