The goal of this clinical trial is to learn the affect of melatonin on sleep, cognitive function, and quality of life (QoL) in patients with cirrhosis and a complication called hepatic encephalopathy (HE). The main questions this study aims to answer are:
* Does taking melatonin increase REM sleep, an important part of healthy sleep that is reduced in cirrhosis? * Does taking melatonin improve cognitive function and reported QoL?
This is a pilot study, where participants will:
* take one month of melatonin, followed by one month of thiamine, which is another supplement but is not suspected to impact sleep significantly. * Undergo cognitive testing and take surveys * Wear a commercial wearable sleep tracker * Have a formal sleep study and salivary melatonin collection at the end of taking each supplement at our sleep center Participants will be blinded, and neither they nor the researchers will know which supplement they are taking first and which they are taking second. They will also be randomized, with half starting with melatonin and the other half starting with thiamine.
Cirrhosis with clinically significant portal hypertension or decompensation defined by Baveno VII criteria [de Franchis R et al 2022]
Adults over age 18
CHE (defined by PHES≤ -4) or previously diagnosed HE
Disturbed sleep, with Pittsburgh Sleep Quality Index (PSQI) ≥5
Use of melatonin regularly (3x per week) if unable/unwilling to discontinue for the study
Inability provide informed consent
Heavy current alcohol use (>7 drinks weekly for women and 14 drinks weekly for men)'
Known prior sleep disorder including obstructive sleep apnea
Crossover
Melatonin tablet 3 mg once daily
Dietary supplementParticipants will be instructed to take 3 mg regular acting (not orally dissolving) melatonin 30 minutes before their anticipated bedtime, nightly for the 30 days preceding analysis of study endpoints.
Thiamine
Dietary supplementParticipants will be instructed to take 100 mg regular acting (not orally dissolving) thiamine 30 minutes before their anticipated bedtime, nightly for the 30 days preceding analysis of study endpoints.
Mean change in rapid eye movement (REM) sleep as a percentage of total sleep measured by polysomnography after melatonin vs thiamine
Prior research by the investigators and other groups have suggested that patients with hepatic encephalopathy have reduced REM sleep, which is a critical sleep phase that contributes to daytime attention, cognition, and mental/emotional wellbeing. Melatonin has been noted in small studies to increase the amount of nightly REM sleep but is understudied in cirrhosis. The primary outcome of this study will be to determine whether relative to thiamine, use of melatonin increases the absolute nightly amount of REM sleep and the percentage of nightly sleep spent in REM. This outcome will be measured by polysomnography, the gold standard for sleep stage determination..
Mean change in total sleep time measured by polysomnography
The mean difference in individuals in total sleep duration after use of melatonin or thiamine
Mean change in deep sleep time measured by polysomnography
The mean difference in individuals in total deep sleep duration and as a percentage of total sleep duration after use of melatonin or thiamine
Mean change in percentage sleep efficiency measured by polysomnography
The mean difference in individuals in sleep efficiency, as measured by % of total time in bed spent asleep after use of melatonin or thiamine
Mean change in wake after sleep onset (WASO) measured by polysomnography
The mean difference in individuals in WASO, as measured by duration (min) of wake time after initial sleep onset after use of melatonin or thiamine
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Weill Medical College of Cornell University
Lead sponsor
American Association for the Study of Liver Diseases
Collaborator
