Does melatonin improve the amount and quality of sleep in patients with early cirrhosis and will it reduce the daytime sleepiness consequently affecting overall quality of life?

Study setting: Gastroenterology & hepatology clinic of the Department of Medicine, University of Kelaniya Located at Colombo North Teaching Hospital Ragama, Sri Lanka.

The subjects of the study will be assigned to 2 groups (intervention & control) by simple randomization.

The intervention group will be given a 3mg dose of melatonin, as single tablet daily (to be taken 30 minutes before their usual bedtime) for 2 weeks.

The control group will receive a starch containing placebo (appearance similar to the intervention drug) as a single tablet daily (to be taken 30 minutes before their usual bedtime) for 2 weeks.

Crossover will be after a washout period of one week from the end of the 1st stage of the trial. The intervention group will be given the placebo and the control group given the intervention drug.

During the trial, both arms of study will be followed up in their usual gastroenterology clinic. The routine medications and investigations will continue as per standard management protocols in cirrhosis.

Participants, Health care providers, data collectors, data analysts, outcome adjudicators will be blinded to the intervention status.

1. Male and female patients aged 18 years and above
2. Patients with a diagnosis of cirrhosis with at least two of the following: compatible clinical features, biochemical evidence or histological evidence
3. Severity of cirrhosis falling under Child-Turcotte-Pugh categories A and B

1. Patients with obstructive sleep apnoea diagnosed by the following criteria will be excluded (a) neck circumference >17 inches for men and >16 inches for women and (b) Positive Berlin questionnaire
2. Having evidence of moderate to severe depression on Beck Depression Inventory (score >20)
3. Other ongoing conditions that affects the central nervous system and sleep patterns including recent cerebrovascular events (within 3 months), uremia
4. Patients who have consumed alcohol within the last 6 weeks or continue to use alcohol
5. Patients with other diseases that interfere with sleep including chronic diarrhoeal conditions, chronic airway disease
6. Cirrhosis of Child Turcotte Pugh class C
7. Presence of hepatic encephalopathy (HE) (Grade II to IV according to West Haven criteria)
8. Patients who complain of having moderate to severe pruritus that interferes with sleep
9. Patients who are on drugs that are directly known to reduce or increase sleep (e.g. antihistamines)
10. Patients who are continuing to use tobacco (known to reduce melatonin levels in blood)
11. As this study has a significant number of interviewer administered tools and in the absence of a native Tamil speaking researcher in the team, exclusively Tamil speaking patients will be excluded
12. Patients with cognitive or psychiatric impairment who are unable to provide an informed consent