To study the effect of ramelteon, a melatonin receptor agonist, on sleep quality, duration
and cognitive function in cirrhotics with insomnia.
Patients with cirrhosis have difficulties with their sleep quality, which adversely affects
their health-related quality of life. It is assumed the sleep disturbances are related to
hepatic encephalopathy (HE) in these patients. However, several recent reports have indicated
that this is not a perfect concordance and that cognition is not related to sleep
disturbance. The mechanism for this change is not clear, although there is evidence of
melatonin-delayed phase in these patients as well as difficulties with the excretion pattern
of cortisol. Ghrelin is an orexigenic hormone produced by the stomach which stimulates the
appetite and also has a profound effect on sleep. Our group has demonstrated a substantial
alteration in ghrelin secretion in cirrhosis that correlates with poor slow-wave sleep. In
healthy individuals, ghrelin injection encourages slow-wave sleep while sleep deprivation
increases ghrelin levels. The role of ghrelin in the sleep disturbances of cirrhosis has not
been determined. Prior studies have also lacked the use of overnight polysomnography as a
tool and have relied on either actigraphy or questionnaires. There is a need for detailed
mechanistic and therapeutic approaches to analyzing sleep disturbances in cirrhosis.
Also the therapy of sleep disturbance in cirrhosis is largely empirical. Prior studies have
evaluated hydroxyzine which runs the risk of precipitating HE. Ramelteon is a melatonin
analog that is FDA-approved for use in insomnia and will potentially be useful to restore the
sleep-wake cycle in cirrhosis-associated sleep disturbance.
The investigators aim to study the impact of the FDA-approved ramelteon on the sleep quality
(using questionnaires and sleep diaries) on these patients with cirrhosis.
Phase:
Phase 4
Details
Lead Sponsor:
Virginia Commonwealth University
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)