Sleep Chronobundle for Circadian Rhythm Disorder

(ReAlign-ICU Trial)

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Melissa P Knauert, MD, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Yale University

Disqualifiers: Chronic brain injury, Diabetes, Hypoglycemia, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests a 'sleep chronobundle' to help ICU patients by improving their sleep and aligning their body clocks. The treatment includes daytime light exposure, timed eating, increased daytime activity, and better nighttime sleep. It aims to enhance sleep quality and metabolic health.

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 data supports the effectiveness of the Sleep Chronobundle treatment for Circadian Rhythm Disorder?

Research shows that bright light therapy, a component of the Sleep Chronobundle treatment, is effective in adjusting sleep-wake cycles for people with circadian rhythm sleep disorders. Additionally, combining light therapy with melatonin has been shown to help align the body's internal clock with desired sleep schedules. ^{1 2 3 4 5}

Is the Sleep Chronobundle treatment generally safe for humans?

Research on melatonin, a component often used in treatments for circadian rhythm disorders, shows it is generally safe for humans. Studies indicate that melatonin does not impair cognitive or motor skills, has no potential for dependence or abuse, and does not cause significant adverse effects compared to a placebo. ^{4 6 7 8 9}

How does the Sleep Chronobundle treatment differ from other treatments for circadian rhythm disorder?

The Sleep Chronobundle treatment is unique because it likely combines multiple approaches, such as light therapy and melatonin administration, to adjust the body's internal clock. This combination aims to optimize the timing and effectiveness of these interventions, which are typically used separately in other treatments for circadian rhythm disorders. ^{1 3 7 10 11}

Research Team

Melissa P Knauert, MD, PhD

Principal Investigator

Yale University

Eligibility Criteria

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.

I am 18 years old or older.

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.

Trial Timeline

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

Treatment Details

Interventions

• Chronobundle - Feeding (Behavioural Intervention)
• Chronobundle - Light (Behavioural Intervention)
• Chronobundle - Mobility (Behavioural Intervention)
• Chronobundle - Sleep (Behavioural Intervention)

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.

Participant Groups

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+

Nancy J. Brown

Yale University

Chief Medical Officer since 2020

MD from Yale School of Medicine

Peter Salovey

Yale University

Chief Executive Officer since 2013

PhD in Psychology from Yale University

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Dr. Gary H. Gibbons

National Heart, Lung, and Blood Institute (NHLBI)

Chief Executive Officer since 2012

MD from Harvard Medical School

Dr. James P. Kiley

National Heart, Lung, and Blood Institute (NHLBI)

Chief Medical Officer since 2011

MD from University of California, San Francisco

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. Japan pubmed.ncbi.nlm.nih.gov

[Diagnosis and treatment in circadian rhythm sleep disorders]. [2013]

2. Australia pubmed.ncbi.nlm.nih.gov

Clinical features of circadian rhythm sleep disorders in outpatients. [2015]

3. Japan pubmed.ncbi.nlm.nih.gov

[Circadian rhythm sleep disorder]. [2014]

4. United States 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. [2022]

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

Pulsing blue light through closed eyelids: effects on acute melatonin suppression and phase shifting of dim light melatonin onset. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Chronobiotics--drugs that shift rhythms. [2019]

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

Promoting adjustment of the sleep-wake cycle by chronobiotics. [2013]

8. Israel 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]. [2013]

9. United States 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. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Circadian-Based Therapies for Circadian Rhythm Sleep-Wake Disorders. [2020]

11. Finland pubmed.ncbi.nlm.nih.gov

[Chronobiological treatments of mood disorders]. [2014]