Melatonin for Liver Cirrhosis

(SNORE-HE Trial)

Overseen By Adam Buckholz, MD MS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Weill Medical College of Cornell University

Must not be taking: Melatonin, Neuromodulating sleep aides

Disqualifiers: Heavy alcohol use, Sleep apnea, others

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

Compensation: Varies

Number of Visits: 2

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if melatonin, a hormone supplement, can improve sleep, thinking skills, and quality of life for individuals with liver cirrhosis and hepatic encephalopathy (HE), a condition affecting the brain. Participants will take melatonin for one month and thiamine, a vitamin, for another month to assess their impact on these areas. The trial requires wearing a sleep tracker and undergoing sleep studies. Ideal candidates have liver cirrhosis, experience sleep difficulties, and own a smartphone compatible with a specific app. As an unphased trial, this study provides a unique opportunity to contribute to understanding how melatonin and thiamine might enhance life quality for those with liver cirrhosis.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot regularly use melatonin or other prescription sleep aids during the study.

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

A previous study demonstrated that melatonin is safe for humans. Participants reported few side effects, with mild sleepiness and dizziness being the most common. Serious side effects were rare. As a natural hormone that helps regulate sleep, melatonin is available over-the-counter for sleep issues, suggesting it is generally safe to use. For those considering joining a trial involving melatonin, its good safety record offers reassurance.

Why are researchers excited about this trial?

Unlike the standard treatments for liver cirrhosis, which often involve managing symptoms with medications like diuretics, beta-blockers, and sometimes liver transplants, melatonin offers a unique approach. Melatonin is primarily known as a sleep hormone, but it has antioxidant and anti-inflammatory properties that could protect liver cells and improve liver function. Researchers are excited because melatonin might address the underlying damage and inflammation in cirrhosis, offering a potential new avenue for treatment that goes beyond just symptom management.

What evidence suggests that melatonin might be an effective treatment for cirrhosis?

Research has shown that melatonin might aid people with liver cirrhosis who struggle with sleep. Studies have found that melatonin can enhance sleep quality and reduce daytime sleepiness in these patients. It appears to protect the liver from damage and lower inflammation, both of which are concerns in liver diseases. Melatonin is also regarded as safe and effective for short-term relief of sleep issues in cirrhosis. In this trial, participants will receive melatonin as part of their treatment regimen. Overall, these findings suggest that melatonin could improve sleep and potentially support liver health in patients with cirrhosis. ^{1 2 3 4 5}

Who Is on the Research Team?

Adam Buckholz, MD MS

Principal Investigator

NewYork-Presbyterian/Weill Cornell Medical College

Are You a Good Fit for This Trial?

This trial is for patients with liver cirrhosis and hepatic encephalopathy who experience sleep disturbances. Participants should be willing to take supplements, undergo cognitive tests, wear a sleep tracker, and participate in a formal sleep study. Details on specific inclusion or exclusion criteria are not provided.

Inclusion Criteria

Possession of a 'smart phone' with Bluetooth capability and ability to download the Oura application (Apple iOS version 14.0 or greater or Android version 8.0 or higher)

I have severe liver disease with significant symptoms.

I am over 18 years old.

Exclusion Criteria

I use melatonin regularly and cannot or do not want to stop for the study.

Inability provide informed consent

Heavy current alcohol use (>7 drinks weekly for women and 14 drinks weekly for men)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

Baseline Assessment

Participants undergo a 2-week run-in for baseline home sleep assessment

2 weeks

Continuous monitoring via wearable tracker

Treatment Phase 1

Participants receive either melatonin or thiamine for 4 weeks, with continuous sleep monitoring and cognitive testing

4 weeks

1 visit for polysomnography and salivary melatonin collection

Washout

Participants undergo a 1-week washout period between treatments

1 week

Treatment Phase 2

Participants receive the alternate treatment (melatonin or thiamine) for 4 weeks, with continuous sleep monitoring and cognitive testing

4 weeks

1 visit for polysomnography and salivary melatonin collection

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Melatonin

Trial Overview The study aims to determine if melatonin improves REM sleep, cognitive function, and quality of life in cirrhotic patients with hepatic encephalopathy. It's a pilot study where participants will alternate between taking melatonin and thiamine over two months without knowing the order.

How Is the Trial Designed?

Group I: Thiamine then melatonin Experimental Treatment 2 Interventions

This group will take one month of melatonin, followed by a one week washout period, then one month of thiamine. They will have the primary outcomes assessed at each month, and will also undergo continuous sleep monitoring via a wearable tracker during all phases of the arm.

Group II: Melatonin then Thiamine Experimental Treatment 2 Interventions

This group will take one month of melatonin, followed by a one week washout period, then one month of thiamine. They will have the primary outcomes assessed at each month, and will also undergo continuous sleep monitoring via a wearable tracker during all phases of the arm.

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

American Association for the Study of Liver Diseases

Collaborator

Trials

7

Recruited

240+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8653678/

Benefits and Risks of Melatonin in Hepatic and Pancreatic ... They have concluded that melatonin in a dose of 3 mg/d seems safe and effective for relief of sleep disturbance in the short term in cirrhotic patients (Child A ...

2. brieflands.com brieflands.com/journals/ijpr/articles/124487.pdf

Benefits and Risks of Melatonin in Hepatic and Pancreatic ... Current evidence shows that melatonin protects against liver injury by inhibiting oxidation, inflammation, hepatic stella cells proliferation, and hepatocyte ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2211383522002945

Melatonin alleviates alcoholic liver disease via EGFR– ... Melatonin alleviates ethanol-induced liver steatosis, cell death, and inflammation through a direct binding and regulation of hepatocyte surface EGFR.

4. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/jgh3.12356

Low‐dose melatonin for sleep disturbances in early‐stage ... Therefore, melatonin improved sleep quality and reduced daytime sleepiness in patients with early-stage cirrhosis. Melatonin was also well ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5412268/

Effects of Melatonin on Liver Injuries and Diseases - PMC Melatonin had beneficial effects on liver injury induced by aflatoxin B1. The apoptotic rate was significantly reduced after melatonin treatment ...