Tailored Lighting and Melatonin for Sleep Disorders in Long COVID

Overseen By Barrie L Harper, BSMT (ASCP) PMP

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Duke University

Must not be taking: Sleep medications

Disqualifiers: Severe visual impairments, photosensitivity, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

600 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how tailored lighting and melatonin can assist individuals with sleep problems related to Long COVID (PASC). The aim is to determine if these treatments can improve issues such as excessive daytime sleepiness (hypersomnia) and nighttime insomnia. Participants will join one of four groups to test various combinations of lighting and melatonin over eight weeks. Individuals experiencing sleep problems due to Long COVID and not using sleep medication might be suitable candidates. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to early findings.

Will I have to stop taking my current medications?

If you are taking sleep medication, you will need to stop taking it for 4 weeks before starting the trial. For other medications, the protocol does not specify any requirements.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that melatonin is generally safe and has been used to treat sleep problems. Studies have found that melatonin can improve sleep quality and may ease symptoms related to COVID-19 due to its antioxidant and anti-inflammatory effects. People taking melatonin have reported only a few mild side effects, such as drowsiness or headaches.

Early research suggests that using specific types of light to influence sleep patterns, known as tailored lighting, is also safe. Studies have shown that light therapy can improve quality of life and reduce tiredness, with few side effects.

Overall, both melatonin and tailored lighting have shown promise in studies and appear to be safe options for helping people with Long COVID who have sleep issues. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer a unique approach to tackling sleep disorders in Long COVID patients. Unlike standard treatments that typically focus on sleep aids or medications like sedatives, this trial uses a combination of tailored lighting and melatonin to adjust circadian rhythms naturally. Tailored lighting helps reset the body's internal clock by simulating natural light patterns, while melatonin, a hormone that regulates sleep, is used to enhance sleep quality. This dual approach aims to address not just the symptoms but the underlying disruptions in sleep-wake cycles caused by Long COVID, offering a potentially more holistic and effective solution.

What evidence suggests that this trial's treatments could be effective for sleep disorders in Long COVID?

Research has shown that melatonin, one of the treatments in this trial, might help people with Long COVID sleep better. A review of several studies found that melatonin can safely and effectively treat sleep problems. It improves sleep patterns and offers health benefits due to its antioxidant properties.

Tailored lighting, another treatment option in this trial, involves changing light exposure to enhance sleep and wake cycles. Studies suggest this method can help people with sleep issues by syncing their internal body clock with natural light. Both treatments in this trial aim to ease sleep problems related to Long COVID by focusing on the body's natural rhythms. Participants will be randomly assigned to one of four groups to receive different combinations of these treatments. ^{1 6 7 8 9}

Who Is on the Research Team?

Christina Barkauskas, MD

Principal Investigator

Duke Clinical Research Institute

Susan Redline, MD MPH

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

This trial is for individuals experiencing sleep disorders after COVID-19, often referred to as Long COVID. Participants should meet the general criteria listed in a related document (NCTXXXXXXXXX). Specific details about who can join are not provided here.

Inclusion Criteria

I meet the main study's requirements for RECOVER-SLEEP.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Baseline assessments are conducted before randomization to intervention groups

1 week

Treatment

Participants receive tailored lighting and melatonin interventions for sleep disturbances

8 weeks

Weekly visits (in-person or virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Melatonin
• Tailored lighting (TL)

Trial Overview The study tests if tailored lighting or melatonin can improve sleep issues in post-COVID patients. It's a multi-center trial where participants are randomly assigned to receive either real treatments or placebos for comparison.

How Is the Trial Designed?

Group I: Active TL + Oral Melatonin Active Control 2 Interventions

The Complex PASC-Related Sleep Disturbances (CPSD) Appendix B combines brief education and a tailored sleep timing prescription for CPSD (referred to as RESET-PASC) with therapies that modify circadian timing for participants who report poor sleep quality. The intervention therapies involve tailored lighting (TL) and melatonin. Participants will be randomly assigned to one of four groups: (a) active TL + oral melatonin, (b) active TL + placebo melatonin, (c) placebo TL + oral melatonin, and (d) placebo TL + placebo melatonin. All groups will receive RESET-PASC. The intervention duration will be 8 weeks.

Group II: Active TL + Placebo Melatonin Active Control 2 Interventions

The Complex PASC-Related Sleep Disturbances (CPSD) Appendix B combines brief education and a tailored sleep timing prescription for CPSD (referred to as RESET-PASC) with therapies that modify circadian timing for participants who report poor sleep quality. The intervention therapies involve tailored lighting (TL) and melatonin. Participants will be randomly assigned to one of four groups: (a) active TL + oral melatonin, (b) active TL + placebo melatonin, (c) placebo TL + oral melatonin, and (d) placebo TL + placebo melatonin. All groups will receive RESET-PASC. The intervention duration will be 8 weeks.

Group III: Placebo TL + Oral Melatonin Active Control 2 Interventions

The Complex PASC-Related Sleep Disturbances (CPSD) Appendix B combines brief education and a tailored sleep timing prescription for CPSD (referred to as RESET-PASC) with therapies that modify circadian timing for participants who report poor sleep quality. The intervention therapies involve tailored lighting (TL) and melatonin. Participants will be randomly assigned to one of four groups: (a) active TL + oral melatonin, (b) active TL + placebo melatonin, (c) placebo TL + oral melatonin, and (d) placebo TL + placebo melatonin. All groups will receive RESET-PASC. The intervention duration will be 8 weeks.

Group IV: Placebo TL + Placebo Melatonin Placebo Group 2 Interventions

The Complex PASC-Related Sleep Disturbances (CPSD) Appendix B combines brief education and a tailored sleep timing prescription for CPSD (referred to as RESET-PASC) with therapies that modify circadian timing for participants who report poor sleep quality. The intervention therapies involve tailored lighting (TL) and melatonin. Participants will be randomly assigned to one of four groups: (a) active TL + oral melatonin, (b) active TL + placebo melatonin, (c) placebo TL + oral melatonin, and (d) placebo TL + placebo melatonin. All groups will receive RESET-PASC. The intervention duration will be 8 weeks.

Melatonin is already approved in European Union, United States for the following indications:

Approved in European Union as Circadin for:

• Insomnia in adults aged 55 and over
• Sleep disorders in children with autism spectrum disorder

Approved in European Union as Slenyto for:

• Insomnia in children and adolescents aged 2-18 with autism spectrum disorder

Approved in United States as Melatonin for:

• Sleep disorders in children with autism spectrum disorder
• Insomnia in adults

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

Published Research Related to This Trial

Tasimelteon is the first FDA-approved medication specifically for non-24-hour sleep-wake disorder, acting as an agonist for melatonin receptors MT1 and MT2 to help regulate sleep cycles.

The drug works by mimicking the natural hormone melatonin, which helps to realign the body's circadian rhythm when it is disrupted, particularly in individuals who do not receive typical light cues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tasimelteon: first global approval. Dhillon, S., Clarke, M.[2022]

Circadian timing significantly affects mental and physical health, and treatments like light therapy and melatonin can help realign misaligned circadian rhythms.

The review discusses various treatment options, including light exposure and melatonin receptor agonists, emphasizing the importance of patient characteristics and safety in choosing the appropriate intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Light and Melatonin and Other Melatonin Receptor Agonists on Human Circadian Physiology. Emens, JS., Burgess, HJ.[2018]

In a study of 13 totally blind subjects, prolonged-release melatonin (PRM) improved mean nightly sleep duration by 43 minutes compared to 16 minutes in the placebo group, suggesting it may help with sleep difficulties in this population.

PRM was well-tolerated with mild to moderate adverse events, and its beneficial effects on sleep persisted even after discontinuation, indicating potential for stabilizing the biological clock.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged release melatonin for improving sleep in totally blind subjects: a pilot placebo-controlled multicenter trial. Roth, T., Nir, T., Zisapel, N.[2022]

Melatonin (MLT) and its receptor agonists, such as ramelteon and agomelatine, have been shown to effectively promote sleep and treat insomnia, although the improvements in sleep maintenance are considered moderate.

Agomelatine not only aids in sleep but also serves as a promising treatment for depression, offering efficacy with a favorable side effect profile, highlighting its potential as a dual-action therapeutic agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Melatonin receptor agonists: new options for insomnia and depression treatment. Spadoni, G., Bedini, A., Rivara, S., et al.[2021]

Melatonin (MLT) is a powerful chronobiotic that can effectively entrain the sleep-wake cycle, particularly in totally blind individuals, by acting on the master circadian clock in the brain.

MLT is not just a sleep hormone but a signal of darkness that influences various circadian rhythms, and its effects are mediated through two receptors (MT1 and MT2), highlighting the potential for developing targeted therapies for sleep and circadian disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Melatonin and the circadian system: Keys for health with a focus on sleep. Pevet, P., Challet, E., Felder-Schmittbuhl, MP.[2021]

Melatonin treatment showed varying efficacy in two patients with non-24 hour sleep-wake syndrome, with one patient experiencing improved sleep onset but no change in sleep-wake rhythm, while the other successfully shifted to a delayed sleep phase pattern.

The effects of melatonin were not consistent over time; after a 4-month break, re-administration did not restore the improved sleep-wake rhythm in the second patient, indicating that while melatonin can be beneficial, its effects may be temporary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Melatonin treatment for rhythm disorder. Kato, M., Kajimura, N., Sekimoto, M., et al.[2015]

Low-dose melatonin treatment can effectively promote sleep onset and maintenance without altering sleep architecture, making it a useful option for individuals with insomnia or circadian rhythm disorders.

High doses of melatonin (over 0.3 mg) may lead to side effects and disrupt circadian rhythms, highlighting the importance of using physiologic doses and ensuring quality control in melatonin supplements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Melatonin, Circadian Rhythms, and Sleep. Zhdanova, IV., Tucci, V.[2020]

In a study involving 8 healthy male volunteers, the high dose (5 mg) of the melatonin agonist LY 156735 significantly improved the speed of physiological readaptation to a 9-hour time shift, indicating its potential effectiveness for treating circadian rhythm disorders.

The high dose also helped reduce performance deterioration associated with shift lag, although subjective well-being measures did not show significant changes with either the high or low doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronobiotic effects of the melatonin agonist LY 156735 following a simulated 9h time shift: results of a placebo-controlled trial. Nickelsen, T., Samel, A., Vejvoda, M., et al.[2019]

Melatonin can effectively phase-shift circadian rhythms and improve sleep in totally blind individuals with non-24 hour sleep/wake disorder, especially when administered at the right time relative to their circadian phase.

Light exposure, particularly short wavelength light, can suppress melatonin production and influence circadian rhythms, indicating that optimizing light's spectral composition may enhance its effectiveness in regulating sleep patterns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimization of light and melatonin to phase-shift human circadian rhythms. Skene, DJ.[2019]

A prototype personal light-treatment device using low brightness blue LEDs was effective in suppressing nocturnal melatonin levels in older adults, with a 60% suppression observed at a high light level after 90 minutes.

The study indicates that higher levels of blue light provide quicker and more sustained melatonin suppression compared to lower levels, suggesting this device could be a practical solution for improving sleep quality in those with circadian sleep disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A personal light-treatment device for improving sleep quality in the elderly: dynamics of nocturnal melatonin suppression at two exposure levels. Figueiro, MG., Bierman, A., Bullough, JD., et al.[2021]

Melatonin significantly reduces the time it takes to fall asleep (by about 7 minutes) and increases total sleep time (by about 8 minutes) in patients with primary sleep disorders, based on a meta-analysis of 19 studies involving 1683 participants.

While the effects of melatonin on sleep quality are modest, it is considered a safer alternative to other insomnia medications due to its benign side-effect profile, making it a viable option for treating sleep issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-analysis: melatonin for the treatment of primary sleep disorders. Ferracioli-Oda, E., Qawasmi, A., Bloch, MH.[2021]

A daily dose of 0.5 mg melatonin effectively entrained the cortisol rhythms in most blind subjects with free-running circadian rhythms, with 7 out of 10 subjects showing positive changes during the treatment period.

Melatonin treatment not only improved sleep duration at night but also reduced daytime napping, suggesting its acute soporific effects may contribute to better sleep quality, especially when administered at the right circadian time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of low-dose 0.5-mg melatonin on the free-running circadian rhythms of blind subjects. Hack, LM., Lockley, SW., Arendt, J., et al.[2022]

Citations

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