SchizophreniaRESPITENCT05956951
Restoring Spindle and Thalamocortical Efficiency in Early-Course Schizophrenia Patients Using Auditory Stimulation
A study testing Closed-loop auditory stimulation in people with Schizophrenia, run by Fabio Ferrarelli at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Schizophrenia
- What is being tested?
- Closed-loop auditory stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 200 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Jul 2023to Jun 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 18 to 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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):
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- 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.
Who cannot join
- General exclusion criteria:
- 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)
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- 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 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
Fabio Ferrarelli, MD, PhD, ferrarellif@upmc.edu
About this study
Official title: Restoring Spindle and Thalamocortical Efficiency in Early-Course Schizophrenia Patients Using Closed-Loop Auditory Stimulation
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.
Read the detailed description
The overarching goal of the proposed study is to establish sleep spindle and slow wave abnormalities as early pathophysiological biomarkers of schizophrenia (SCZ). The investigators also seek to enhance spindle and slow wave deficits in EC-SCZ by utilizing a closed-loop auditory stimulation during sleep. The investigators will assess improvement of deficits with the use of a memory consolidation task before and after sleeping.
Participants will include early-course schizophrenia (EC-SCZ) subjects and healthy controls (HC). Participants will complete several assessments, including clinical evaluation, an IQ assessment (WASI), and at least 2 nights of sleep EEG recordings in the sleep clinic of UPMC Western Psychiatric Hospital with a polysomnography test (PSG) each night. Study participants will also fill out a Pittsburgh Sleep Quality Index (PSQI) which reports sleep habits. On one of the nights, EC-SCZ participants will receive active closed-loop auditory stimulation, while on another night they will receive sham closed-loop auditory stimulation. On all nights beside the adaptation night (night 1) participants will complete the motor sequence task (MST) and the AX-continuous performance task (AXCPT) before going to sleep. They will also repeat the task the following morning. There will be ~1 week between nights 2 and 3 and ~1 week between nights 3 and 4.
Aim 1. Establish sleep spindle and slow wave deficits in EC-SCZ patients relative to HC using a wireless ambulatory monitor.
H1a. EC-SCZ patients will have reduced sleep spindle duration and density compared to HC.
H1b. Slow wave density will be decreased in EC-SCZ patients relative to HC.
Aim 2. Determine that spindle and slow wave impairments can be acutely improved in EC-SCZ patients using closed-loop auditory stimulation during sleep.
H2a. Sleep spindle duration and density will increase during closed-loop auditory stimulation nights compared to baseline and sham intervention.
H2b. Slow wave density will increase during stimulation nights relative to baseline and sham intervention.
Aim 3. Examine the relationship between spindle and slow wave deficits and memory consolidation before and after their acute improvement in EC-SCZ patients relative to HC.
H3a. At baseline, sleep spindles and slow waves will predict memory consolidation in EC-SCZ patients and HC.
H3b. An increase in sleep spindles and slow waves during stimulating night will be associated with task-assessed memory consolidation improvement in EC-SCZ patients relative to baseline performance.
- Conditions
- Schizophrenia
- Being tested
- Closed-loop auditory stimulation, Sham auditory stimulation
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Closed-loop auditory stimulationDevice
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.
Sham auditory stimulationDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Device: Closed-loop auditory stimulation; Device: Sham auditory stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: baseline (pre closed-loop auditory stimulation), study completion (up to 6 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2023
- Study start20 Jul 2023
- Primary completionJun 2028 (estimated)
- Study completionJun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SchizophreniaStudies 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
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fabio Ferrarelli
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor-investigator, Fabio Ferrarelli, University of Pittsburgh
- Investigators
- Fabio Ferrarelli, MD,PhD, Principal investigator, University of Pittsbrugh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05956951
- Sponsor's protocol ID
- STUDY20010236
- Other IDs
- R01MH130376
- Acronym
- RESPITE
- Status last verified
- Jun 2026
- First submitted
- 15 Jun 2023
- Last updated
- 4 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: This study will comply with current National Institute of Mental Health (NIMH) data sharing rules as defined in NOT-MH-19-033 and will share all collected data in the National Database for Clinical Trials Related to Mental Illness (NDCT) database consistent with current guidelines and according to the schedule set in these guidelines.
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Restoring Spindle and Thalamocortical Efficiency in Early-Course Schizophrenia Patients Using Closed-Loop Auditory Stimulation
- ClinicalTrials.gov ID
- NCT05956951
- Acronym / sponsor ID
- RESPITE / STUDY20010236
- Conditions
- Schizophrenia
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Fabio FerrarelliUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 20 Jul 2023 (actual)
- Primary completion
- Jun 2028 (estimated)
- Study completion
- Jun 2028 (estimated)
- First posted
- 24 Jul 2023 (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.
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.
Detailed description
The overarching goal of the proposed study is to establish sleep spindle and slow wave abnormalities as early pathophysiological biomarkers of schizophrenia (SCZ). The investigators also seek to enhance spindle and slow wave deficits in EC-SCZ by utilizing a closed-loop auditory stimulation during sleep. The investigators will assess improvement of deficits with the use of a memory consolidation task before and after sleeping.
Participants will include early-course schizophrenia (EC-SCZ) subjects and healthy controls (HC). Participants will complete several assessments, including clinical evaluation, an IQ assessment (WASI), and at least 2 nights of sleep EEG recordings in the sleep clinic of UPMC Western Psychiatric Hospital with a polysomnography test (PSG) each night. Study participants will also fill out a Pittsburgh Sleep Quality Index (PSQI) which reports sleep habits. On one of the nights, EC-SCZ participants will receive active closed-loop auditory stimulation, while on another night they will receive sham closed-loop auditory stimulation. On all nights beside the adaptation night (night 1) participants will complete the motor sequence task (MST) and the AX-continuous performance task (AXCPT) before going to sleep. They will also repeat the task the following morning. There will be ~1 week between nights 2 and 3 and ~1 week between nights 3 and 4.
Aim 1. Establish sleep spindle and slow wave deficits in EC-SCZ patients relative to HC using a wireless ambulatory monitor.
H1a. EC-SCZ patients will have reduced sleep spindle duration and density compared to HC.
H1b. Slow wave density will be decreased in EC-SCZ patients relative to HC.
Aim 2. Determine that spindle and slow wave impairments can be acutely improved in EC-SCZ patients using closed-loop auditory stimulation during sleep.
H2a. Sleep spindle duration and density will increase during closed-loop auditory stimulation nights compared to baseline and sham intervention.
H2b. Slow wave density will increase during stimulation nights relative to baseline and sham intervention.
Aim 3. Examine the relationship between spindle and slow wave deficits and memory consolidation before and after their acute improvement in EC-SCZ patients relative to HC.
H3a. At baseline, sleep spindles and slow waves will predict memory consolidation in EC-SCZ patients and HC.
H3b. An increase in sleep spindles and slow waves during stimulating night will be associated with task-assessed memory consolidation improvement in EC-SCZ patients relative to baseline performance.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental: Night three- sham, night four - active | Experimental | Device: Closed-loop auditory stimulation, Device: Sham auditory stimulationThis 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 |
| Experimental: Night three - active, night four - sham | Experimental | Device: Closed-loop auditory stimulation, Device: Sham auditory stimulationThis 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 |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- 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
- ages 18-40 years
Key exclusion criteria (15 listed)
- 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)
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 |
|---|---|---|
| Closed-loop auditory stimulationClosed-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. | Device | Experimental: Night three - active, night four - sham, Experimental: Night three- sham, night four - active |
| Sham auditory stimulationSham 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. | Device | Experimental: Night three - active, night four - sham, Experimental: Night three- sham, night four - active |
Primary outcome
Deficits in sleep spindle and slow wave density in early-course schizophrenia patients (EC-SCZ).
Time frame: baseline (pre closed-loop auditory stimulation)
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.
Deficits in sleep spindle and slow wave duration in early-course schizophrenia patients (EC-SCZ).
Time frame: baseline (pre closed-loop auditory stimulation)
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.
Deficits in sleep spindle and slow wave amplitude in early-course schizophrenia patients (EC-SCZ).
Time frame: baseline (pre closed-loop auditory stimulation)
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.
Improvement in sleep spindle and slow wave density.
Time frame: baseline (pre closed-loop auditory stimulation), study completion (up to 6 weeks)
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.
Improvement in sleep spindle and slow wave duration.
Time frame: baseline (pre closed-loop auditory stimulation), study completion (up to 6 weeks)
Changes in sleep spindle and slow wave duration (measured in seconds) in EC-SCZ patients before and after closed-loop auditory stimulation during sleep.
Improvement in sleep spindle and slow wave amplitude.
Time frame: baseline (pre closed-loop auditory stimulation), study completion (up to 6 weeks)
Changes in sleep spindle and slow wave amplitude (measured in microvolts) in EC-SCZ patients before and after closed-loop auditory stimulation during sleep.
Relationship between spindle and slow wave deficits and memory consolidation.
Time frame: baseline (pre closed-loop auditory stimulation), study completion (up to 6 weeks)
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2026.
- Individual participant dataSharing planned: Yes. This study will comply with current National Institute of Mental Health (NIMH) data sharing rules as defined in NOT-MH-19-033 and will share all collected data in the National Database for Clinical Trials Related to Mental Illness (NDCT) database consistent with current guidelines and according to the schedule set in these guidelines.
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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.
Fabio Ferrarelli, MD,PhD principal investigator
University of Pittsbrugh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Closed-loop auditory stimulation in people with Schizophrenia, run by Fabio Ferrarelli at 1 site in United States.
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 15 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: looking for participants now, as of the sponsor's last update on 4 Jun 2026. 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 United States. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Chloe A Huston, MA (412-246-6114, hustonca@upmc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Deficits in sleep spindle and slow wave density in early-course schizophrenia patients (EC-SCZ). (time frame: baseline (pre closed-loop auditory stimulation)). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Jun 2026.