Acoustic Stimulation for Depression

(SERS Trial)

Overseen By Michelle E Stepan, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Pittsburgh

Must not be taking: Antidepressants, Antipsychotics, Steroids, Stimulants

Disqualifiers: Psychosis, Bipolar, Substance use, others

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

Compensation: Varies

Number of Visits: 4

40 Participants Needed

Trial Summary

What is the purpose of this trial?

In this study, the investigators will recruit young adults (ages 18-25 years) with elevated anxiety/depression symptoms and sleep disturbance. Participants will complete two overnights in a sleep lab. During one of the overnights, slow-wave activity will be enhanced by delivering sub-arousal auditory tones during slow-wave sleep using a headband device (Philips SmartSleep or Dreem 2). During the other overnight, tones will not be administered. Cognitive and emotional processes will be evaluated using behavioral task performance, self-report, and functional magnetic resonance imaging (fMRI). After the second overnight, participants will take the headband device home and wear it every night for approximately 2 weeks. For half of the participants, the headband will play tones every night and, for the other half, the headband will not play tones. Participants will then return for a final testing visit in which cognitive and emotional processes and anxiety/depression symptoms will be assessed using behavioral task performance and self-report.

Do I need to stop taking my current medications for the trial?

Yes, you will need to stop taking any psychotropic medications or medications affecting sleep/wake function, such as antidepressants, antipsychotic medications, steroids, and stimulants, as these may affect sleep and cognitive-emotional function.

What data supports the effectiveness of the treatment Acoustic Stimulation for Depression?

Research shows that auditory stimulation can increase REM sleep time and improve sleep efficiency in healthy individuals, which might suggest potential benefits for mood regulation. However, in depressed patients, auditory stimulation did not lead to clinical improvements, indicating that its effectiveness for depression specifically is not supported by current evidence. ^{1 2 3 4 5}

Is acoustic stimulation generally safe for humans?

The research does not provide specific safety data for acoustic stimulation in humans for depression, but studies on similar treatments like Electric-Acoustic Stimulation (EAS) in adults with hearing loss suggest it is generally safe. ^{4 6 7 8 9}

How does acoustic stimulation treatment for depression differ from other treatments?

Acoustic stimulation for depression is unique because it uses sound therapy to potentially influence sleep patterns and neural processes, unlike standard treatments like medication or therapy. This non-invasive approach aims to enhance sleep efficiency and memory processing, offering a novel alternative without the side effects associated with drugs. ^{1 2 5 10 11}

Research Team

Michelle E Stepan, PhD

Principal Investigator

University of Pittsburgh

Eligibility Criteria

Young adults aged 18-25 with normal hearing, experiencing anxiety or depression and sleep disturbances can join. They must not use drugs/alcohol before sessions, have extreme sleep schedules, vision issues, claustrophobia, metal in the body, a BMI over 40, severe insomnia/sleep apnea symptoms or be pregnant.

Inclusion Criteria

I am between 18 and 25 years old.

Elevated anxiety or depression symptoms determined using the PROMIS anxiety and PROMIS depression scales with T-scores ≥ 60

I have normal hearing.

Exclusion Criteria

Short (<5hrs) or long (>9hrs) average sleep duration

Substance abuse

I have severe insomnia or symptoms of sleep apnea.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Online survey and in-person baseline visit

Baseline and Acclimation

Participants complete baseline assessments and acclimate to the headband device

1 week

1 in-person visit, daily sleep diary entries

Overnight Sessions

Participants undergo two overnight sessions with acoustic stimulation and sham conditions

2 weeks

2 overnight visits

At-home Phase

Participants use the headband device at home for approximately 2 weeks with daily assessments

2 weeks

Daily at-home use and assessments

Follow-up

Participants return for a final testing visit to assess cognitive and emotional processes

1 day

1 in-person visit

Treatment Details

Interventions

• Acoustic Stimulation
• Daily acoustic stimulation
• No Acoustic Stimulation
• No daily acoustic stimulation

Trial Overview The trial tests if acoustic stimulation during sleep affects cognitive-emotional processes in those with anxiety/depression. Participants wear a headband at night that may play tones to enhance slow-wave activity; effects are measured through tasks and self-reports.

Participant Groups

Group I: Stim, then Sham, then daily Stim Experimental Treatment 3 Interventions

For the 2 overnights in the sleep lab, this arm will be randomized to complete acoustic stimulation (STIM) on the first overnight and no acoustic stimulation (SHAM) on the second overnight and then daily acoustic stimulation (STIM2) during the \~2 weeks at-home.

Group II: Stim, then Sham, then daily Sham Experimental Treatment 3 Interventions

For the 2 overnights in the sleep lab, this arm will be randomized to complete acoustic stimulation (STIM) on the first overnight and no acoustic stimulation (SHAM) on the second overnight and then no daily acoustic stimulation (SHAM2) during the \~2 weeks at-home.

Group III: Sham, then Stim, then daily Stim Experimental Treatment 3 Interventions

For the 2 overnights in the sleep lab, this arm will be randomized to complete no acoustic stimulation (SHAM) on the first overnight and acoustic stimulation (STIM) on the second overnight and then daily acoustic stimulation (STIM2) during the \~2 weeks at-home.

Group IV: Sham, then Stim, then daily Sham Experimental Treatment 3 Interventions

For the 2 overnights in the sleep lab, this arm will be randomized to complete no acoustic stimulation (SHAM) on the first overnight and acoustic stimulation (STIM) on the second overnight and then no daily acoustic stimulation (SHAM2) during the \~2 weeks at-home.

Who Is Running the Clinical Trial?

University of Pittsburgh

Lead Sponsor

Trials

1,820

Recruited

16,360,000+

Michelle Stepan

Lead Sponsor

Trials

1

Recruited

40+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Brain & Behavior Research Foundation

Collaborator

Trials

63

Recruited

2,900+

Findings from Research

In a study involving normal volunteers and depressed patients, auditory stimulation during REM sleep significantly increased REM sleep time and sleep efficiency in normal volunteers who received stimulation during each REM episode (Group R).

Depressed patients did not experience increased REM sleep time with auditory stimulation, but they did have shorter REM episodes and more frequent awakenings, indicating that the effects of auditory stimulation may differ based on the individual's mental health status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of auditory stimulation during rapid eye movement sleep in healthy volunteers and depressed patients. Salin-Pascual, RJ., Granados-Fuentes, D., de la Fuente, JR., et al.[2019]

Auditory stimulation during slow-wave sleep (SWS) significantly enhances neural oscillations, such as slow oscillations and sleep spindles, which are crucial for memory consolidation in various populations, including healthy individuals and those with conditions like ADHD and depression.

This technique not only improves the quality of sleep-related memory processing but also shows potential for manipulating REM sleep theta oscillations, indicating a broader application for enhancing memory benefits through targeted auditory stimulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sounding It Out: Auditory Stimulation and Overnight Memory Processing. Harrington, MO., Cairney, SA.[2022]

This paper provides a comprehensive overview of how acoustic stimuli can be used to enhance sleep, discussing various methods, their advantages and disadvantages, and the differences in outcomes measured, such as subjective versus objective effects.

It highlights the importance of considering individual differences and environmental factors when studying the effects of acoustic input on sleep, suggesting that both therapeutic and adverse acoustic influences can significantly impact sleep quality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated Review of the Acoustic Modulation of Sleep: Current Perspectives and Emerging Concepts. Cordi, MJ.[2021]

In a study of 124 outpatients with chronic tinnitus, the addition of low-level white noise generators (NG) to cognitive-behavioral treatment (CBT) did not enhance treatment outcomes, indicating that psychological interventions alone are effective.

All participants showed significant improvements in tinnitus-related distress and other psychological measures, but the NGs only benefited those with both tinnitus and hyperacusis, suggesting that physical stimulation may not be necessary for effective tinnitus management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does sound stimulation have additive effects on cognitive-behavioral treatment of chronic tinnitus? Hiller, W., Haerkötter, C.[2022]

In a well-conducted trial involving 236 participants with major depression, the Alpha-Stim AID device was found to be safe, with only 7% reporting adverse events, but it did not show any significant clinical effectiveness compared to a sham device.

Both the active and sham groups experienced similar reductions in depression symptoms, indicating that the Alpha-Stim AID device is not more effective than placebo in treating major depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical effectiveness of active Alpha-Stim AID versus sham Alpha-Stim AID in major depression in primary care in England (Alpha-Stim-D): a multicentre, parallel group, double-blind, randomised controlled trial. Morriss, R., Patel, S., Boutry, C., et al.[2023]

Electric-acoustic stimulation (EAS) significantly improved speech recognition in noise for children with severe-to-profound high-frequency hearing loss compared to acoustic- and electric-only stimulation, especially in challenging listening environments.

Children using EAS preferred it over electric-only stimulation and their teachers noted enhanced hearing performance in classroom settings, indicating its practical benefits in everyday situations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential Benefits of an Integrated Electric-Acoustic Sound Processor with Children: A Preliminary Report. Wolfe, J., Neumann, S., Schafer, E., et al.[2020]

The MED-EL Electric-Acoustic Stimulation (EAS) System is shown to be a safe and effective treatment for adults with low-frequency hearing and severe-to-profound hearing loss in higher frequencies, with 92% of participants completing the study and 97% able to use the acoustic unit after 12 months.

At 12 months postactivation, 94% of subjects performed as well or better on speech perception tests in noise compared to their preoperative performance, indicating significant improvements in hearing capabilities with the EAS system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter US Clinical Trial With an Electric-Acoustic Stimulation (EAS) System in Adults: Final Outcomes. Pillsbury, HC., Dillon, MT., Buchman, CA., et al.[2019]

A new miniaturized ultrasound brain stimulator operating at 10 MHz was developed for small animal models, allowing for precise stimulation of specific brain areas while minimizing interference with auditory pathways.

This platform demonstrated that focal stimulation of the visual and barrel cortex in mice resulted in significantly higher neuronal activity, with calcium signal levels two to three times greater than in surrounding areas, showcasing its efficacy in monitoring brain functions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Soft Housing Needle Ultrasonic Transducer for Focal Stimulation to Small Animal Brain. Choi, T., Bae, S., Suh, M., et al.[2020]

In a study involving seven patients with preserved hearing after cochlear implantation, electric acoustic stimulation (EAS) was found to significantly improve speech intelligibility scores compared to full electrical stimulation (FES) and electrical complement (EC), indicating its efficacy in enhancing hearing performance.

The majority of participants (71.4%) preferred EAS over the other stimulation modes, suggesting that EAS may be the most favorable option for adults with prior hearing aid experience, while younger patients or those with less hearing aid use may prefer FES.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary study to determine an optimal mode for favorable residual hearing at low frequencies: Full electrical stimulation, electric acoustic stimulation, and electrical complement. Jang, JH., Kim, H., Choo, OS., et al.[2022]

This clinical trial investigates a non-surgical method of vagus nerve stimulation (tVNS) on the ear to treat major depressive disorder (MDD) in 120 patients, aiming to provide a safer alternative to traditional VNS, which requires surgery.

The study could broaden the use of VNS for MDD and other conditions, potentially offering long-term mood regulation benefits without the risks associated with surgical interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous vagus nerve stimulation for the treatment of depression: a study protocol for a double blinded randomized clinical trial. Rong, PJ., Fang, JL., Wang, LP., et al.[2022]

Cranial electrical stimulation (CES) has been suggested as a treatment for acute depression with minimal adverse effects, but this systematic review found no studies that met the criteria for rigorous evaluation.

The authors concluded that there is a significant lack of methodologically sound research on CES for depression, highlighting the need for more double-blind randomized controlled trials to assess its efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alternating current cranial electrotherapy stimulation (CES) for depression. Kavirajan, HC., Lueck, K., Chuang, K.[2023]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Effects of auditory stimulation during rapid eye movement sleep in healthy volunteers and depressed patients. [2019]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Sounding It Out: Auditory Stimulation and Overnight Memory Processing. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Updated Review of the Acoustic Modulation of Sleep: Current Perspectives and Emerging Concepts. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Does sound stimulation have additive effects on cognitive-behavioral treatment of chronic tinnitus? [2022]

5. England pubmed.ncbi.nlm.nih.gov

Clinical effectiveness of active Alpha-Stim AID versus sham Alpha-Stim AID in major depression in primary care in England (Alpha-Stim-D): a multicentre, parallel group, double-blind, randomised controlled trial. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Potential Benefits of an Integrated Electric-Acoustic Sound Processor with Children: A Preliminary Report. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Multicenter US Clinical Trial With an Electric-Acoustic Stimulation (EAS) System in Adults: Final Outcomes. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

A Soft Housing Needle Ultrasonic Transducer for Focal Stimulation to Small Animal Brain. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

Preliminary study to determine an optimal mode for favorable residual hearing at low frequencies: Full electrical stimulation, electric acoustic stimulation, and electrical complement. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Transcutaneous vagus nerve stimulation for the treatment of depression: a study protocol for a double blinded randomized clinical trial. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Alternating current cranial electrotherapy stimulation (CES) for depression. [2023]