Sleep Chronobundle for Circadian Rhythm Disorder

(ReAlign-ICU Trial)

Recruiting at 1 trial location

Overseen By Melissa P Knauert, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Yale University

Disqualifiers: Chronic brain injury, Diabetes, Hypoglycemia, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 72 hours

160 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach to help ICU patients improve sleep and overall health by aligning their internal clocks with natural rhythms. The treatment, known as a "chronobundle," involves managing light exposure, meal timing, exercise, and sleep schedules. The researchers aim to determine if better alignment of the body's natural rhythms can enhance sleep quality and metabolic health in critically ill patients. Suitable participants include those in the ICU needing machine support for breathing or circulation. As an unphased trial, this study offers a unique opportunity to contribute to innovative research that could improve ICU care.

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

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your healthcare provider.

What prior data suggests that this sleep chronobundle is safe for patients with circadian rhythm disorder?

Research shows that treatments like the "sleep chronobundle," which aim to improve sleep and synchronize body clocks, are generally safe. The chronobundle includes bright light during the day, scheduled meals, exercise, and sleep support. It is designed to help people in the ICU, where sleep and body clock disruptions are common.

Studies on similar treatments have shown they are well-tolerated. For example, using light therapy and managing sleep schedules has not caused serious side effects. Evidence also indicates that melatonin, often used in these treatments, does not lead to major negative reactions.

Overall, existing research considers these strategies safe. Participants can expect few, if any, negative side effects, making it a promising option for improving sleep and health in the ICU. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Sleep Chronobundle for Circadian Rhythm Disorder because it takes a holistic approach by combining bright daytime light, time-restricted feeding, enhanced exercise, and overnight sleep promotion. This method stands out because it doesn't just focus on one aspect of treatment but addresses multiple lifestyle factors that influence circadian rhythms. Unlike standard treatments that might rely on medication to adjust sleep patterns, the Chronobundle emphasizes natural interventions that could offer a more sustainable and side-effect-free way to reset the body's internal clock. This multifaceted approach has the potential to significantly improve patients' circadian rhythms and overall health.

What evidence suggests that this trial's treatments could be effective for circadian rhythm disorder?

This trial will compare the effects of a comprehensive treatment approach called the Chronobundle with usual ICU care. Research has shown that aligning the body's internal clock can enhance sleep and improve food processing. Studies have found that bright light therapy, combined with planned meal times and exercise, can reset the natural sleep-wake cycle. Specifically, using bright light in the morning and eating at set times can improve sleep patterns. These methods have been shown to facilitate falling asleep, enhance sleep quality, and reduce symptoms of sleep disorders. Such strategies may aid recovery in healthcare settings, potentially benefiting ICU patients with sleep difficulties. ^{1 2 6 7 8}

Who Is on the Research Team?

Melissa P Knauert, MD, PhD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for adult patients recently admitted to the MICU who are intubated and not expected to be extubated within 24 hours. It's not suitable for those with severe brain injuries, circadian disorders, recent shift work, homelessness, high risk of aspiration or hypoglycemia issues.

Inclusion Criteria

I am on a breathing machine and haven't passed a breathing test.

Patients admitted to the intensive care unit within 24 hours of 9:00 on the day of enrollment.

Exclusion Criteria

I am at high risk for low blood sugar episodes.

You have a high chance of having existing sleep pattern issues due to severe brain injury, circadian disorder, recent shift work, homelessness, being in jail, or living in an institution.

You are not expected to produce more than 250 milliliters of urine in a day.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive the sleep chronobundle intervention, including bright daytime light, time-restricted feeding, increased mobility, and overnight sleep promotion

72 hours

Continuous monitoring in ICU

Follow-up

Participants are monitored for safety and effectiveness after treatment, including metrics such as sleep and glucose metabolism

14 days

Daily assessments in ICU

Long-term Follow-up

Participants are monitored for outcomes such as ventilator-free days, time to hospital discharge, and mortality

30 days

What Are the Treatments Tested in This Trial?

Interventions

• Chronobundle - Feeding
• Chronobundle - Light
• Chronobundle - Mobility
• Chronobundle - Sleep

Trial Overview The study tests a 'chronobundle' approach in ICU patients to align sleep and eating patterns with natural body clock rhythms. The goal is to see if this improves sleep quality and metabolic function by promoting normal circadian alignment.

How Is the Trial Designed?

Group I: Chronobundle Experimental Treatment 4 Interventions

The chronobundle will include bright daytime light, time-restricted intermittent feeding, enhanced exercise/mobility, and overnight sleep promotion.

Group II: Control Active Control 1 Intervention

Usual ICU care.

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

A comprehensive review of circadian rhythm sleep disorders (CRSDs) highlights effective evaluation methods, including physiological assessments like core body temperature and melatonin timing, as well as behavioral assessments such as sleep logs and actigraphy.

Treatment options for CRSDs include prescribed sleep schedules, circadian phase shifting, and medications, but the success of these interventions varies, indicating a need for further research with subjects meeting current diagnostic criteria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circadian rhythm sleep disorders: part II, advanced sleep phase disorder, delayed sleep phase disorder, free-running disorder, and irregular sleep-wake rhythm. An American Academy of Sleep Medicine review. Sack, RL., Auckley, D., Auger, RR., et al.[2022]

Primary circadian rhythm sleep disorder (CRSD) cases were diagnosed at a younger age and showed a better response to treatments like vitamin B12 and bright light therapy compared to secondary CRSD cases, which often had underlying psychiatric or medical conditions.

The majority of primary CRSD cases were delayed sleep phase syndrome (83.7%), while secondary CRSD cases had a more varied pattern, indicating different underlying mechanisms and treatment responses between the two types of disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical features of circadian rhythm sleep disorders in outpatients. Yamadera, W., Sasaki, M., Itoh, H., et al.[2015]

A study using blue light pulses delivered through a sleep mask showed significant melatonin suppression, indicating its potential effectiveness in regulating circadian rhythms in older adults.

In a field study, these blue light pulses were found to effectively delay circadian phase in older adults, suggesting that this method of light therapy could be a practical and compliant treatment for sleep disorders at home.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulsing blue light through closed eyelids: effects on acute melatonin suppression and phase shifting of dim light melatonin onset. Figueiro, MG., Plitnick, B., Rea, MS.[2022]

Chronobiotics, like melatonin, can help adjust internal biological rhythms and are increasingly being explored for treating sleep disturbances related to circadian rhythm changes, such as jet lag and shift work sleep disorders.

While there is agreement on the potential of melatonin to shift the circadian clock, more research is needed to determine the best dosage, formulation, and timing for administration to maximize its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Promoting adjustment of the sleep-wake cycle by chronobiotics. Touitou, Y., Bogdan, A.[2013]

Chronobiological treatments are non-drug approaches that aim to regulate circadian rhythms and sleep patterns to help treat psychiatric disorders, particularly mood disorders like depression.

These treatments involve techniques such as manipulating sleep-wake cycles and controlling light exposure, but their clinical application in Finland has been limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chronobiological treatments of mood disorders]. Urrila, AS., Partonen, T.[2014]

Melatonin (MLT) is highlighted as a powerful chronobiotic that can help reset the circadian pacemaker, making it a promising treatment for various sleep disturbances like jet lag and shift work-related issues.

Both human and animal studies support the efficacy of MLT in managing circadian rhythm disorders, suggesting it could serve as a valuable alternative or supplement to light therapy for improving sleep patterns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronobiotics--drugs that shift rhythms. Dawson, D., Armstrong, SM.[2019]

Circadin, a prolonged-release melatonin formulation, effectively improves sleep quality and reduces sleep latency in patients aged 55 and over with primary insomnia, showing benefits in next-day alertness and overall quality of life.

Unlike traditional sedative hypnotics, Circadin does not impair cognitive or psychomotor skills, has no risk of dependence or abuse, and has a favorable safety profile with no significant adverse events compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Controlled release melatonin (Circadin) in the treatment of insomnia in older patients: efficacy and safety in patients with history of use and non-use of hypnotic drugs]. Zisapel, N.[2013]

Recent guidelines and studies highlight effective treatments for various circadian rhythm sleep-wake disorders, including delayed sleep-wake phase disorder and shift work, emphasizing the importance of personalized approaches.

Innovative methods for estimating circadian phase, such as home saliva collection for melatonin onset and new light treatment technologies, show promise in improving treatment outcomes for these disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circadian-Based Therapies for Circadian Rhythm Sleep-Wake Disorders. Burgess, HJ., Emens, JS.[2020]

Circadian rhythm sleep disorders (CRSD) occur when there is a mismatch between a person's natural sleep patterns and their desired sleep times, often due to disruptions in the body's internal clock located in the brain.

Effective treatments for CRSD include light therapy and melatonin supplements, particularly for those with delayed sleep phase disorder, along with proper sleep hygiene practices that consider the light environment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Diagnosis and treatment in circadian rhythm sleep disorders]. Murakami, J., Imai, M., Yamada, N.[2013]

Circadian rhythm sleep disorders (CRSDs) arise from a mismatch between the body's internal clock and the desired sleep schedule, and they can be effectively treated with chronotherapy using bright light and melatonin.

Bright light therapy is particularly effective as it can shift the sleep-wake cycle, helping to realign the circadian rhythm with social or personal sleep requirements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Circadian rhythm sleep disorder]. Mishima, K.[2014]

A comprehensive review of circadian rhythm sleep disorders (CRSDs) highlights effective evaluation methods, including physiological assessments like core body temperature and melatonin timing, as well as behavioral assessments such as sleep logs and actigraphy.

Treatment options for shift work disorder (SWD) and jet lag disorder (JLD) include prescribed sleep schedules, circadian phase shifting techniques, and medications, though the success of these interventions varies and more research is needed to refine them.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circadian rhythm sleep disorders: part I, basic principles, shift work and jet lag disorders. An American Academy of Sleep Medicine review. Sack, RL., Auckley, D., Auger, RR., et al.[2022]

Citations

1. withpower.com withpower.com/trial/phase-sleep-wake-disorders-3-2023-bb0be

Sleep Chronobundle for Circadian Rhythm Disorder This trial tests a 'sleep chronobundle' to help ICU patients by improving their sleep and aligning their body clocks.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9886819/

Treatment of Circadian Rhythm Sleep–Wake Disorders - PMC A recent study showed that 0.5 mg of melatonin combined with behavioral wake-up scheduling can advance sleep onset time, improve sleep quality, and reduce sleep ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03682185

NCT03682185 | The Healthy Patterns Sleep Study The Healthy Patterns Study intervention is a home-based activity intervention designed to improve symptoms of circadian rhythm disorders (CRD) and quality ...

4. atm.amegroups.org atm.amegroups.org/article/view/114541/html

Enhancing circadian rhythms—the circadian MEGA bundle as ... A MEGA bundle consisting of intense light therapy each morning, cyclic nutrition support, timed physical therapy, nighttime melatonin administration.

5. atsjournals.org atsjournals.org/doi/10.1164/rccm.202301-0184ST

American Journal of Respiratory and Critical Care Medicine Sleep and circadian rhythms are believed to play an important role in recovery from injury and illness. Sleep quality and quantity are linked to mortality in ...

6. trialx.com trialx.com/clinical-trials/listings/291129/reestablishing-sleep-and-circadian-alignment-in-medical-intensive-care-unit-micu-patients-via-a-mechanistic-rct-of-an-sleep-chronobundle/

Reestablishing Sleep and Circadian Alignment in Medical ... This project will test the ability of a sleep chronobundle (i.e., sleep promotion and circadian treatment bundle) to normalize circadian ...

7. reporter.nih.gov reporter.nih.gov/project-details/10892022

Project Details - NIH RePORTER This project will test the ability of a sleep chronobundle (i.e., sleep promotion and circadian treatment bundle) to normalize circadian alignment and ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03247062

Sleep Bundle for Improving Sleep in ICU Patients The project " sleep bundle " aims at improving the sleep of the patients by the implementation of a multimodal intervention that consists in a ...