Effect of Supplemental Nightly Melatonin On REM and Cognition in Hepatic Encephalopathy (SNORE-HE) Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Mean change in rapid eye movement (REM) sleep as a percentage of total sleep measured by polysomnography after melatonin vs thiamine
研究概览
简要总结
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.
详细描述
Study Objectives
This project aims to determine the impact of melatonin supplementation on sleep physiology in patients with cirrhosis and HE.
Hypothesis: Melatonin supplementation will improve sleep physiology, and REM specifically.
Background and Significance
Hepatic encephalopathy (HE) affects approximately 50% of patients with cirrhosis, causing lasting cognitive and quality of-life impairments even with therapy. Most HE cases are covert, significantly increasing risks of hospitalization, mortality, and progression to overt HE (OHE) within three years (>50%). Guidelines recommend screening all patients for covert HE (CHE) using neurocognitive tools such as the Psychomotor Hepatic Encephalopathy Score (PHES). However, low screening and treatment rates persist due to the need for specialized training, equipment, and significant time commitments. Even in patients receiving HE therapy, clinicians are hesitant to escalate treatment absent overt confusion, largely due to the cost and poor tolerability of rifaximin and lactulose. These limitations contribute to frequent hospital readmissions and high short-term mortality in those with prior OHE. Improved recognition and management strategies are critical to advancing HE outcomes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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)
排除标准
- •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)'
- •-- Body mass index >40
- •Known prior sleep disorder including obstructive sleep apnea
- •Use of other prescription neuromodulating sleep aides
- •Self-reported pregnancy during study screening, as sleep physiology is different in this population
研究组 & 干预措施
Melatonin then Thiamine
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.
干预措施: Melatonin tablet 3 mg once daily (Dietary Supplement)
Thiamine then melatonin
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.
干预措施: Melatonin tablet 3 mg once daily (Dietary Supplement)
Thiamine then melatonin
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.
干预措施: Thiamine (Dietary Supplement)
Melatonin then Thiamine
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.
干预措施: Thiamine (Dietary Supplement)
结局指标
主要结局
Mean change in rapid eye movement (REM) sleep as a percentage of total sleep measured by polysomnography after melatonin vs thiamine
时间窗: Approximately 4 weeks and 9 weeks, at polysomnography which marks the end of each treatment (melatonin or thiamine) assignment.
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 rapid eye movement (REM) sleep as a percentage of total sleep measured by polysomnography after melatonin vs thiamine
时间窗: Approximately 4 weeks and 9 weeks, at polysomnography which marks the end of each treatment (melatonin or thiamine) assignment.
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..
次要结局
- Mean change in total sleep time measured by polysomnography(Approximately 4 weeks and 9 weeks, at polysomnography which marks the end of each treatment (melatonin or thiamine) assignment.)
- Mean change in deep sleep time measured by polysomnography(Approximately 4 weeks and 9 weeks, at polysomnography which marks the end of each treatment (melatonin or thiamine) assignment)
- Mean change in percentage sleep efficiency measured by polysomnography(approximately 4 weeks and 9 weeks, at polysomnography which marks the end of each treatment (melatonin or thiamine) assignment)
- Mean change in wake after sleep onset (WASO) measured by polysomnography(approximately 4 weeks and 9 weeks, at polysomnography which marks the end of each treatment (melatonin or thiamine) assignment)
- Mean change in resting and mean heart rate during sleep measured by polysomnography(approximately 4 weeks and 9 weeks, at polysomnography which marks the end of each treatment (melatonin or thiamine) assignment)
- Mean change in total sleep time measured by Oura 3.0(Entire duration of study period (visit 1-3). Approximately week 0-9)
- Mean change in rapid eye movement (REM) sleep as a percentage of total sleep measured by Oura 3.0 ring after melatonin vs thiamine(Entire duration of study period (visit 1-3). Approximately week 0-9)
- Mean change in deep sleep time measured by Oura 3.0(Entire duration of study period (visit 1-3). Approximately week 0-9)
- Mean change in percentage sleep efficiency measured by Oura 3.0(Entire duration of study period (visit 1-3). Approximately week 0-9)
- Mean change in average and resting heart rate during sleep measured by Oura 3.0(Entire duration of study period (visit 1-3). Approximately week 0-9)
- Mean change in sleep midpoint as measured by Oura 3.0(Entire duration of study period (visit 1-3). Approximately week 0-9)
- Variation in sleep midpoint as measured by Oura 3.0(Entire duration of study period (visit 1-3). Approximately week 0-9)
- Variation in body temperature as measured by Oura 3.0(Entire duration of study period (visit 1-3). Approximately week 0-9)
- Mean change in sleep onset time as measured by Oura 3.0(Entire duration of study period (visit 1-3). Approximately week 0-9)
- Mean change in cognitive performance as measured by Psychometric Hepatic Encephalopathy Score (PHES)(At time of polysomnography (Approximately week 4 and week 9))
- Correlation in measurement of heart rate between polysomnography and Oura 3.0 ring(Entire time of concomitant measurement with both devices (Oura/PSG), which is during each polysomnography, approximately weeks 4 and 9.)
- Mean difference in subjective sleep quality as measured by Pittsburgh Sleep Quality Index (PSQI)(At time of polysomnography (Approximately week 4 and week 9))
- Mean difference in health related quality of life as measured by PROMIS-29 v2.0 PROPr(At time of polysomnography (Approximately week 4 and week 9))
- Mean change in pre-bedtime to awake salivary melatonin levels in participants after 4 weeks of treatment with melatonin or thiamine as measured at time of polysomnography(At time of polysomnography (Approximately week 4 and week 9))
- Correlation in measurement of deep sleep determination between polysomnography and Oura 3.0 ring(Entire time of concomitant measurement with both devices (Oura/PSG), which is during each polysomnography, approximately weeks 4 and 9.)
- Correlation in measurement of light sleep determination between polysomnography and Oura 3.0 ring(Entire time of concomitant measurement with both devices (Oura/PSG), which is during each polysomnography, approximately weeks 4 and 9.)
- Correlation in measurement of rapid eye movement (REM) sleep determination between polysomnography and Oura 3.0 ring(Entire time of concomitant measurement with both devices (Oura/PSG), which is during each polysomnography, approximately weeks 4 and 9.)
- Correlation in measurement of awake/sleep determination between polysomnography and Oura 3.0 ring(Entire time of concomitant measurement with both devices (Oura/PSG), which is during each polysomnography, approximately weeks 4 and 9.)
- Mean change in total sleep time measured by polysomnography(Approximately 4 weeks and 9 weeks, at polysomnography which marks the end of each treatment (melatonin or thiamine) assignment.)
- Mean change in wake after sleep onset (WASO) measured by polysomnography(approximately 4 weeks and 9 weeks, at polysomnography which marks the end of each treatment (melatonin or thiamine) assignment)
- Mean change in pre-bedtime to awake salivary melatonin levels in participants after 4 weeks of treatment with melatonin or thiamine as measured at time of polysomnography(At time of polysomnography (Approximately week 4 and week 9))
- Correlation in measurement of deep sleep determination between polysomnography and Oura 3.0 ring(Entire time of concomitant measurement with both devices (Oura/PSG), which is during each polysomnography, approximately weeks 4 and 9.)
- Mean change in rapid eye movement (REM) sleep as a percentage of total sleep measured by Oura 3.0 ring after melatonin vs thiamine(Entire duration of study period (visit 1-3). Approximately week 0-9)
- Mean change in sleep midpoint as measured by Oura 3.0(Entire duration of study period (visit 1-3). Approximately week 0-9)
- Mean change in cognitive performance as measured by Psychometric Hepatic Encephalopathy Score (PHES)(At time of polysomnography (Approximately week 4 and week 9))
- Mean difference in subjective sleep quality as measured by Pittsburgh Sleep Quality Index (PSQI)(At time of polysomnography (Approximately week 4 and week 9))
- Mean change in deep sleep time measured by polysomnography(Approximately 4 weeks and 9 weeks, at polysomnography which marks the end of each treatment (melatonin or thiamine) assignment)
- Mean change in percentage sleep efficiency measured by polysomnography(approximately 4 weeks and 9 weeks, at polysomnography which marks the end of each treatment (melatonin or thiamine) assignment)
- Mean change in resting and mean heart rate during sleep measured by polysomnography(approximately 4 weeks and 9 weeks, at polysomnography which marks the end of each treatment (melatonin or thiamine) assignment)
- Variation in sleep midpoint as measured by Oura 3.0(Entire duration of study period (visit 1-3). Approximately week 0-9)
- Variation in body temperature as measured by Oura 3.0(Entire duration of study period (visit 1-3). Approximately week 0-9)
- Correlation in measurement of light sleep determination between polysomnography and Oura 3.0 ring(Entire time of concomitant measurement with both devices (Oura/PSG), which is during each polysomnography, approximately weeks 4 and 9.)
- Mean change in total sleep time measured by Oura 3.0(Entire duration of study period (visit 1-3). Approximately week 0-9)
- Mean change in sleep onset time as measured by Oura 3.0(Entire duration of study period (visit 1-3). Approximately week 0-9)
- Mean change in deep sleep time measured by Oura 3.0(Entire duration of study period (visit 1-3). Approximately week 0-9)
- Mean change in percentage sleep efficiency measured by Oura 3.0(Entire duration of study period (visit 1-3). Approximately week 0-9)
- Mean change in average and resting heart rate during sleep measured by Oura 3.0(Entire duration of study period (visit 1-3). Approximately week 0-9)
- Correlation in measurement of rapid eye movement (REM) sleep determination between polysomnography and Oura 3.0 ring(Entire time of concomitant measurement with both devices (Oura/PSG), which is during each polysomnography, approximately weeks 4 and 9.)
- Correlation in measurement of awake/sleep determination between polysomnography and Oura 3.0 ring(Entire time of concomitant measurement with both devices (Oura/PSG), which is during each polysomnography, approximately weeks 4 and 9.)
- Mean difference in health related quality of life as measured by PROMIS-29 v2.0 PROPr(At time of polysomnography (Approximately week 4 and week 9))
- Correlation in measurement of heart rate between polysomnography and Oura 3.0 ring(Entire time of concomitant measurement with both devices (Oura/PSG), which is during each polysomnography, approximately weeks 4 and 9.)