Auditory Stimulation During Sleep for Schizophrenia

Overseen By Dara Manoach, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Massachusetts General Hospital

Must be taking: APDs

Must not be taking: Psychotropic medications

Disqualifiers: Neurological disorders, Chronic conditions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to assist people with schizophrenia by using gentle sounds during sleep, known as closed-loop auditory stimulation. The goal is to determine if these sounds can enhance brain communication during sleep, potentially boosting memory. Participants will wear a special headband at home that plays these sounds on certain nights. Individuals with schizophrenia who are either unmedicated or on stable medication and can perform a finger-tapping task may qualify. The trial also includes a group of healthy participants without mental health issues. As an unphased study, this trial provides a unique opportunity to explore innovative treatment methods and contribute to groundbreaking research.

Will I have to stop taking my current medications?

If you have schizophrenia and are on a stable dose of antipsychotic drugs, you can continue taking them. However, if you are a healthy adult, you cannot participate if you are currently using psychotropic medications or medications that affect sleep or thinking.

What prior data suggests that this auditory stimulation technique is safe for use during sleep?

Research has shown that using gentle sounds during sleep, known as closed-loop auditory stimulation, is generally well-tolerated. In studies, participants reported no major side effects from this method. The technique involves playing soft sounds to align with the brain's natural rhythms, potentially improving memory by boosting brain activity during sleep.

Although specific data on its safety for people with schizophrenia is limited, existing research has not identified any major safety issues. The trial's advanced stage suggests confidence in the treatment's safety based on previous studies.

Overall, using sounds during sleep appears to be a safe and non-invasive option, with no significant side effects reported in past research. ^{1 2 3 4}

Why are researchers excited about this trial?

Researchers are excited about using closed loop auditory stimulation during sleep for schizophrenia because it offers a completely new approach by targeting sleep patterns. Unlike traditional treatments that often rely on medications to manage symptoms, this method uses sound to enhance brain activity during sleep, potentially improving cognitive function. This non-invasive technique could offer a safer alternative with fewer side effects, addressing a critical need for innovative strategies in managing schizophrenia.

What evidence suggests that this auditory stimulation is effective for schizophrenia?

This trial will compare the effects of closed-loop auditory stimulation during sleep between two groups: adults with schizophrenia and healthy controls. Research has shown that using closed-loop auditory stimulation during sleep can enhance certain brain activities in people with schizophrenia. This method increases slow oscillation and spindle activity, which are important for good sleep. However, previous studies did not find improvements in memory for schizophrenia patients using this technique. The method works by playing gentle sounds at specific times during sleep to help brain rhythms sync better. While it hasn't yet shown clear memory benefits, it remains a promising area of research for improving brain communication during sleep. ^{1 4 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-45 who have been diagnosed with schizophrenia. Participants will use a sleep headband at home to test if auditory stimulation during sleep can improve brain coordination and memory. They must be able to undergo MRI scans and perform a motor sequence task.

Inclusion Criteria

Additional inclusion for Adults with schizophrenia: DSM-V confirmed diagnosis of schizophrenia

Fluent in English

I have schizophrenia and am not on medication or have been on a stable dose.

Exclusion Criteria

Additional Exclusion Criteria for Healthy adults: History of mental illness

IQ <85

I have a neurological condition or seizures.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Baseline Assessment

Participants undergo a daytime MRI scan and complete a finger tapping motor sequence task (MST)

1 day

1 visit (in-person)

Home Sleep Monitoring

Participants wear sleep headbands at home for multiple nights, with auditory stimulation on some nights

5 nights

Follow-up Assessment

Participants return for a second MRI scan and complete post-stimulation assessments

1 day

1 visit (in-person)

Follow-up

Participants are monitored for changes in hippocampal microstructural integrity and functional connectivity

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Closed loop auditory stimulation during sleep

Trial Overview The study tests whether soft sounds played through a sleep headband during specific times in the night can enhance brain network communication in individuals with schizophrenia, potentially leading to improved memory.

How Is the Trial Designed?

Group I: Schizophrenia Experimental Treatment 1 Intervention

Adult outpatients with a diagnosis of schizophrenia.

Group II: Healthy Controls Active Control 1 Intervention

Adult participants screened to exclude a personal history of mental illness, family history of schizophrenia spectrum disorder, and psychoactive medication use.

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Published Research Related to This Trial

In a study involving 18 patients with schizophrenia, real-time auditory stimulation during sleep successfully increased slow wave and sleep spindle activity, similar to responses seen in healthy individuals.

Despite the positive electrophysiological changes, the auditory stimulation did not lead to any improvement in memory performance, indicating that while the approach shows promise, it currently does not enhance memory consolidation in patients with schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Auditory stimulation in-phase with slow oscillations to enhance overnight memory consolidation in patients with schizophrenia? Weinhold, SL., Lechinger, J., Timm, N., et al.[2022]

A novel auditory closed-loop stimulation technique was successfully used to manipulate theta activity during REM sleep in a study involving 16 healthy young adults, demonstrating the ability to entrain EEG activity to 5 Hz.

The stimulation led to an initial increase in theta power followed by a prolonged suppression, along with an increase in beta power, suggesting potential for further research into the effects of REM sleep on behavior.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase-locked auditory stimulation of theta oscillations during rapid eye movement sleep. Harrington, MO., Ashton, JE., Ngo, HV., et al.[2021]

In a pilot study involving 18 patients with schizophrenia and refractory auditory hallucinations, low-frequency deep transcranial magnetic stimulation (TMS) was administered, but results showed no significant difference in improvement between the active treatment and sham groups.

Despite initial encouraging results, the study concluded that this specific TMS protocol did not have a statistically significant effect on reducing auditory hallucinations or improving other clinical symptoms in the patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep transcranial magnetic stimulation add-on for the treatment of auditory hallucinations: a double-blind study. Rosenberg, O., Gersner, R., Klein, LD., et al.[2022]

Closed-loop auditory stimulation can enhance sleep rhythms, specifically increasing delta, theta, and sigma power during non-rapid eye movement (NREM) sleep, which is crucial for brain recovery and memory consolidation.

The study found that this stimulation specifically improved the coupling between delta and sigma activity in the right parietal area, suggesting a targeted approach to enhance sleep-dependent neuroplasticity in specific brain regions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in cross-frequency coupling following closed-loop auditory stimulation in non-rapid eye movement sleep. Krugliakova, E., Volk, C., Jaramillo, V., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11009689/

The effects of closed-loop auditory stimulation on sleep ... In schizophrenia, CLASS increased SO activity and spindle activity that was phase-locked to the SO upstate but failed to improve declarative memory [18]. Both ...

2. academic.oup.com academic.oup.com/sleep/article-abstract/43/Supplement_1/A45/5847500

0113 Evaluating Closed-Loop Auditory Stimulation During ... If it does, we will test the effects of stimulation on sleep-dependent memory deficits in patients with schizophrenia. Closed-loop auditory ...

3. researchgate.net researchgate.net/publication/341683246_0113_Evaluating_Closed-Loop_Auditory_Stimulation_During_Sleep_as_an_Intervention_to_Improve_Memory_Consolidation_Deficits_in_Schizophrenia

0113 Evaluating Closed-Loop Auditory Stimulation During ... If it does, we will test the effects of stimulation on sleep-dependent memory deficits in patients with schizophrenia. Closed-loop auditory stimulation ...

4. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/jsr.13636

Auditory stimulation in‐phase with slow oscillations to ... The mean (SEM, range) age was 40.7 (2.2, 23–53) years. In all, 11 patients had paranoid schizophrenia and seven had a schizoaffective psychosis.

5. mdpi.com mdpi.com/2076-3425/14/11/1138

Closed-Loop Auditory Stimulation (CLAS) During Sleep ... Exclusion criteria included current intoxication or illness at intake or during the study, self-reported chronic brain or mental illness including epilepsy ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06386588

The Effects of Auditory Stimulation During Sleep on Brain ... Adult participants screened to exclude a personal history of mental illness, family history of schizophrenia spectrum disorder, and psychoactive medication use.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7316628/

Targeting sleep oscillations to improve memory in schizophrenia Auditory stimulation during sleep has also been employed to improve memory. This method has the advantages of evoking endogenous oscillations ...