Restoring Spindle and Thalamocortical Efficiency in Early-Course Schizophrenia Patients Using Auditory Stimulation

NCT05956951 | Recruiting FDA Device

• 2 other identifiers: STUDY20010236R01MH130376
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research is to identify differences in brain activity during sleep between health individuals and individuals with schizophrenia, schizophreniform, or schizoaffective disorder. This study will also investigate whether tones played during deep sleep can enhance specific features of sleep and whether enhancing such features is related to an improvement in cognitive performance.

Conditions

Schizophrenia

Outcome Measures

Primary Outcomes (7)

• Deficits in sleep spindle and slow wave density in early-course schizophrenia patients (EC-SCZ).

  The difference between sleep spindle and slow wave density (measured as count per minute) in EC-SCZ relative to HC as recorded on a wireless ambulatory monitor.

  baseline (pre closed-loop auditory stimulation)

• Deficits in sleep spindle and slow wave duration in early-course schizophrenia patients (EC-SCZ).

  The difference between sleep spindle and slow wave duration (measured in seconds) in EC-SCZ relative to HC as recorded on a wireless ambulatory monitor.

  baseline (pre closed-loop auditory stimulation)

• Deficits in sleep spindle and slow wave amplitude in early-course schizophrenia patients (EC-SCZ).

  The difference between sleep spindle and slow wave amplitude (measured in microvolts) in EC-SCZ relative to HC as recorded on a wireless ambulatory monitor.

  baseline (pre closed-loop auditory stimulation)

• Improvement in sleep spindle and slow wave density.

  Changes in sleep spindle and slow wave density (measured as count per minute) in EC-SCZ patients before and after closed-loop auditory stimulation during sleep.

  baseline (pre closed-loop auditory stimulation), study completion (up to 6 weeks)

• Improvement in sleep spindle and slow wave duration.

  Changes in sleep spindle and slow wave duration (measured in seconds) in EC-SCZ patients before and after closed-loop auditory stimulation during sleep.

  baseline (pre closed-loop auditory stimulation), study completion (up to 6 weeks)

• Improvement in sleep spindle and slow wave amplitude.

  Changes in sleep spindle and slow wave amplitude (measured in microvolts) in EC-SCZ patients before and after closed-loop auditory stimulation during sleep.

  baseline (pre closed-loop auditory stimulation), study completion (up to 6 weeks)

• Relationship between spindle and slow wave deficits and memory consolidation.

  Changes in task-assessed memory consolidation scores before and after closed-loop auditory stimulation in EC-SCZ compared to controls. Percent change in number of correct sequences in the morning compared to previous night on the Motor Sequence Tapping (MST) task will provide a proxy measure of overnight memory consolidation. Higher scores on the MST represent better performance.

  baseline (pre closed-loop auditory stimulation), study completion (up to 6 weeks)

Study Arms (2)

Experimental: Night three- sham, night four - active

EXPERIMENTAL

This arm will receive sham auditory stimulation for the first 3 nights and active auditory stimulation for the fourth night. Night one - sham auditory stimulation, night 2 - sham auditory stimulation, night 3 - sham auditory stimulation, night 4 - active auditory stimulation

Device: Closed-loop auditory stimulation; Device: Sham auditory stimulation

Experimental: Night three - active, night four - sham

EXPERIMENTAL

This arm will receive sham auditory stimulation for the first two nights, active auditory stimulation for the third night, and sham auditory stimulation for the fourth night. Night one - sham auditory stimulation, night two - sham auditory stimulation, night three - active auditory stimulation, night four - sham auditory stimulation

Device: Closed-loop auditory stimulation; Device: Sham auditory stimulation

Interventions

Closed-loop auditory stimulation DEVICE

Closed-loop auditory stimulation will be administered by a wearable EEG device (Philips SmartSleep Deep Sleep Headband). The EEG device will deliver auditory stimulation when slow-wave (deep) sleep is detected. Auditory stimulation will consist of 50ms long tones separated from each other by a fixed one-second inter-tone interval. The volume of each tone will be linearly modulated by sleep-depth such that louder (or softer) tones were played during deeper (or shallower) sleep.

Experimental: Night three - active, night four - sham; Experimental: Night three- sham, night four - active

Sham auditory stimulation DEVICE

Sham auditory stimulation consists of closed-loop auditory stimulation not being administered. A wearable EEG device (Philips SmartSleep Deep Sleep Headband) will not deliver closed-loop auditory stimulation and tones will not be played.

Experimental: Night three - active, night four - sham; Experimental: Night three- sham, night four - active

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Early-course schizophrenia (EC-SCZ):
• ages 18-40 years
• current DSM-IV defined diagnosis of schizophrenia, schizophreniform or schizoaffective disorder, not drug-induced, with no previously reported psychotic episode
• duration of ≤5 years from beginning of psychosis, defined by report of symptoms and/or history of treatment according to clinical guidelines employed in our University of Pittsburgh Medical Center (UPMC) psychoses clinics in Pittsburgh
• lifetime exposure to antipsychotic medications ≤5 years
• Healthy controls (HC):
• ages 18-40 years
• no lifetime history of psychiatric disorders
• no first-degree family history of schizophrenia spectrum disorder or mood disorder with psychotic features.

You may not qualify if:

• DSM-IV intellectual disability
• significant head injury
• medical illness affecting brain function or structure
• pregnancy or postpartum (\<6 weeks after delivery or miscarriage)
• significant neurological disorder (e.g. seizure disorder)
• inability to provide informed consent
• current or past co-morbidity for alcohol or psychoactive substance dependence
• substance abuse other than cannabis and/or alcohol within the past one year
• For EC-SCZ:
• a) a psychotic illness with a temporal relation to substance use or head injury
• For healthy controls (HC):
• difficult falling and/or staying asleep for more than half the nights of a week, on average
• diagnosis of sleep apnea or restless leg syndrome
• sleeping less than 5 hours or more than 10 hours daily, on average

Sponsors & Collaborators

• Fabio Ferrarelli: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

MeSH Terms

Conditions

Schizophrenia

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Study Officials

• Fabio Ferrarelli, MD,PhD

  University of Pittsbrugh

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chloe A Huston, MA

CONTACT

412-246-6114; hustonca@upmc.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: June 15, 2023
• First Posted: July 24, 2023
• Study Start: July 20, 2023
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: June 5, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Time Frame: Data will become available January 15th, 2024, and be updated every 6 months. Data will remain infinitely available.
• Access Criteria: Everyone with a NIMH Data Archive login will be able to access the data.

Locations

US (1)