Targeting Insomnia from Within

Millions of people worldwide who suffer with chronic insomnia are all too familiar with its profound impact on cognitive function, mood, and overall health and well-being. Many of these patients have success with first-line treatments like cognitive behavioral therapy (CBT) and pharmacological interventions, but relief remains elusive for many with treatment-resistant insomnia.

While there’s no universal definition for treatment-resistant insomnia, this term generally describes chronic insomnia that fails to respond meaningfully to two or more first-line therapies.1 Researchers sometimes refer to it as refractory insomnia, residual insomnia, or persistent insomnia.1 

A novel treatment approach, PROSOMNIA Sleep Therapy™, shows promise as a new therapeutic option for individuals suffering from treatment-resistant insomnia by targeting its underlying physiological causes.

Advances in research have given us a more sophisticated understanding of the neurological underpinnings that contribute to chronic insomnia—specifically, its connections to impaired glymphatic function in the brain, particularly in the clearance of adenosine, a sleep-regulating neurochemical. 

PROSOMNIA Sleep Therapy works by inducing REM sleep through monitored anesthesia care and enhancing the brain’s natural waste-clearance mechanisms. In a small study of 20 volunteers with chronic insomnia, participants experienced remarkable results after treatment. Sleep onset latency was reduced by 85 percent, while sleep efficiency improved by 98 percent, alongside measurable gains in cognitive function and daytime alertness.  

In this article, we’ll explore how this intervention works, review the methodology and findings of this preliminary research, and look ahead to a larger clinical trial that is now underway. 

How Glymphatic Clearance Works

The glymphatic system, a recently discovered waste-clearance pathway in the brain, plays a critical role in maintaining neural health by removing metabolic waste during sleep.2-5 Specifically, during REM sleep, the glymphatic system becomes particularly active, clearing out byproducts like adenosine.6 

Adenosine is a key regulator of sleep pressure, and its buildup is associated with the onset of fatigue and sleep.6 In cases of chronic insomnia, disrupted glymphatic clearance may lead to the retention of adenosine, thereby increasing sleep pressure and perpetuating insomnia symptoms.7 Standard treatments do not directly address this physiological cause. 

By optimizing REM sleep, PROSOMNIA Sleep Therapy is designed to enhance glymphatic clearance and reduce adenosine levels, providing a more targeted solution for sleep disorders beyond conventional treatments.

Figure. A Closer Look at the Glymphatic System

This illustration of the glymphatic system demonstrates how it clears metabolic waste like adenosine from the brain by promoting the flow of cerebrospinal fluid (CSF) along para-arterial spaces and drainage of interstitial fluid (ISF) along para-venous pathways.

Evaluating Treatment Feasibility

To evaluate the efficacy of PROSOMNIA Sleep Therapy in improving sleep parameters and reducing adenosine-related sleep pressure, PROSOMNIA conducted an unofficial study with 20 voluntary participants diagnosed with treatment-resistant chronic insomnia.* 

Participants were recruited through the PROSOMNIA Sleep Health & Wellness Center in Aventura, Fla., where the study was conducted. Each participant underwent one therapy session, which utilized Diprivan/Propofol to induce REM sleep. The sessions lasted between 60 to 120 minutes, depending on the patient’s individual response to the therapy. 

The therapy was conducted under monitored anesthesia care to ensure patient safety. Patients were monitored for any adverse reactions to the anesthesia, and all reported a safe and comfortable experience during the session.

During the procedure, electroencephalogram (EEG) monitoring was used to verify that patients entered and maintained REM sleep, the stage most critical for glymphatic clearance. In addition to EEG monitoring, blood serum samples were collected from participants both before and after the therapy to measure changes in adenosine levels. 

Previous studies have highlighted the importance of the glymphatic system in removing metabolic waste during sleep, but this study is among the first to directly measure changes in adenosine levels in response to a targeted sleep therapy. 

Subjective sleep quality was assessed using self-reported measures of sleep onset latency, sleep efficiency, and overall sleep satisfaction. These measures were complemented by objective data from the EEG recordings, including REM sleep duration.

*IRB approval was not obtained or feasible for this study. However, this “off-label” therapy was conducted with the full informed consent of all voluntary participants. The unofficial study adhered to the ethical principles outlined in the Declaration of Helsinki for human research. Although this study did not receive formal IRB approval, the procedures followed were designed to uphold the ethical standards for human research and protect the rights and welfare of participants.

Strong Early Evidence

Initial results suggest that PROSOMNIA Sleep Therapy provides rapid, measurable benefits across multiple sleep parameters. Analysis of the data showed that patients demonstrated immediate and significant improvements in sleep onset latency, sleep efficiency, and subjective sleep quality. EEG measurements confirmed extended REM sleep duration, with reductions in adenosine levels post-treatment. 

Additionally, participants reported improvements in subjective sleep quality, with reduced daytime fatigue and enhanced cognitive function. These self-reported outcomes were consistent with the objective measures collected during the study, further validating the efficacy of the therapy.

Key outcome metrics included:

Sleep onset latency: On average, participants experienced an 85 percent reduction in sleep onset latency, demonstrating the therapy’s effectiveness in helping patients fall asleep more quickly.

Sleep efficiency: Sleep efficiency, defined as the percentage of time spent asleep while in bed, increased by 98 percent post-therapy, showing that patients were able to maintain sleep for longer durations after the intervention.

Adenosine levels: Blood serum analysis revealed a 99 percent reduction in adenosine levels, supporting the hypothesis that enhancing glymphatic function during REM sleep can effectively clear excess adenosine, thereby reducing sleep pressure.

REM sleep duration: On average, EEG data confirmed a 30 percent increase in REM sleep duration compared to baseline levels, a critical factor for optimizing glymphatic clearance.

Together, these findings support the emerging hypothesis that glymphatic dysfunction—particularly in the clearance of adenosine—plays a central role in the pathophysiology of chronic insomnia. 

That said, some limitations of this early research must be acknowledged. The study involved a relatively small sample size of 20 participants, and the short follow-up period leaves questions about the long-term sustainability of these effects. Ongoing research will address these limitations to further validate the efficacy of PROSOMNIA Sleep Therapy. 

Further Study Ahead

Preliminary findings suggest that PROSOMNIA Sleep Therapy may offer a valuable new treatment option for individuals with treatment-resistant insomnia. With minimal specialized monitoring requirements, the therapy is both accessible and scalable for outpatient settings—qualities that make it a feasible option for widespread clinical use.

Further clinical trials are necessary to validate these findings and evaluate long-term efficacy, safety, and treatment durability. One such trial is already underway: “Evaluating the Efficacy and Safety of PROSOMNIA Sleep Therapy™ in Patients with Sleep Deprivation and Chronic Insomnia (PSHW)” (NCT06644573). This trial will include a larger, more diverse population and will incorporate extended follow-up assessments to provide a clearer picture of the therapy’s sustained impact. 

As additional data emerge, researchers aim to determine whether this novel approach can reliably improve sleep and daytime function for those who have not benefited from standard treatments or who would like to augment their current treatment regimen. 

By Nyree Penn, MHSc, CAA

Source: SleepWorld Magazine Jul/Aug Issue

 

 

 

 

Nyree Penn, MHSc, CAA, is founder and chief executive officer of PROSOMNIA Sleep Health and Wellness in Aventura, Fla. She would like to express her gratitude to the “Dream Team” at PROSOMNIA Sleep Health & Wellness-Aventura™ for their invaluable assistance in patient care and data collection.

References

1. Akinnusi ME, El-Solh AA. Treatment-resistant insomnia: a common undefined condition. Am J Med. 2021;134(12):1447-8. doi: 10.1016/j.amjmed.2021.06.043.
2. Xie L, Kang H, Xu Q, et al. Sleep drives metabolite clearance from the adult brain. Science. 2013;342(6156):373-7. doi:10.1126/science.1241224.
3. Yi T, Gao P, Zhu T, Yin H, Jin S. Glymphatic system dysfunction: a novel mediator of sleep disorders and headaches. Front Neurol. 2022;13:885020. doi:10.3389/fneur.2022.885020.
4. Bohr T, Hjorth PG, Holst SC, et al. The glymphatic system: current understanding and modeling. iScience. 2022;25(9):104987. doi:10.1016/j.isci.2022.104987.
5. Horsburgh K, Wardlaw JM, van Agtmael T, et al. Small vessels, dementia and chronic diseases – molecular mechanisms and pathophysiology. Clin Sci (Lond). 2018;132(8):851-68. doi:10.1042/CS20171620.
6. Ding F, O’Donnell J, Xu Q, Kang N, Goldman N, Nedergaard M. Changes in the composition of brain interstitial ions control the sleep-wake cycle. Science. 2016;352(6285):550-5. doi:10.1126/science.aad4821.
7. Huang L, Zhu W, Li N, et al. Functions and mechanisms of adenosine and its receptors in sleep regulation. Sleep Med. 2024;115:210-7. doi: 10.1016/j.sleep.2024.02.012
8. Image courtesy of: Quintin S, Barpujari A, Mehkri Y, Hernandez J, Lucke-Wold B. The glymphatic system and subarachnoid hemorrhage: disruption and recovery. Explor Neuroprot Ther. 2022;2:118–30. https://doi.org/10.37349/ent.2022.00023

Author Disclosure

This article discusses the off-label use of Diprivan/Propofol in PROSOMNIA Sleep Therapy™ for inducing REM sleep. PROSOMNIA Sleep™ LLC, PROSOMNIA Sleep Health & Wellness™, and the proprietary PROSOMNIA Sleep Therapy™ discussed in this article are the intellectual property of PROSOMNIA Sleep™, LLC, and are intended for commercial use with the potential for financial gain. 

All interests, innovations, and related intellectual property of PROSOMNIA Sleep™, LLC, and its affiliates are the sole and exclusive rights of PROSOMNIA Sleep™, LLC. The statements in this article have not been approved by the U.S. Food and Drug Administration. This article and its contents are not intended as medical advice and should not replace consultation with a health care professional. Any reference to scientific data or methodology has been independently developed by PROSOMNIA Sleep™, LLC, and does not imply endorsement or approval by any third-party entity. The author holds a financial interest in the success of PROSOMNIA Sleep™, LLC and all affiliations.

Image courtesy of: Quintin S, Barpujari A, Mehkri Y, Hernandez J, Lucke-Wold B. The glymphatic system and subarachnoid hemorrhage: disruption and recovery. Explor Neuroprot Ther. 2022;2:118–30. https://doi.org/10.37349/ent.2022.00023

Related Posts

Unlocking Therapeutic Potential: Targeting Sleep to Combat Neurodegenerative Diseases and Aging

New AASM Guideline: Management of REM Sleep Behavior Disorder in Adults

UCLA Study Links Length of REM Sleep to Body Temperature

Five Year Study Confirms Efficacy of Central Sleep Apnea Therapy Device

More Than a Number: Sleep Quality Is the Next Target for Cardiovascular Health