Efficacy and Safety of Lemborexant for Patients With Cirrhosis and Sleep Problems

Safety and Efficacy of Lemborexant for Patients With Cirrhosis and Sleep Problems: a Randomized Clinical Trial

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT07480096

Enrollment

Registered

2026-03-18

Start date

2024-10-01

Completion date

2025-10-30

Last updated

2026-03-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cirrhosis, Hepatic Encephalopathy, Insomnia, Liver Cirrhosis, Sleep Quality

Keywords

cirrhosis, liver, sleep, orexin, lemborexant, insomnia, sleep quality, safety, efficacy

Brief summary

Sleep disturbance poses significant in patients with liver cirrhosis and is associated with impaired quality of life and worsening clinical status. Current pharmacological options remain limited and often have safety concerns due to altered hepatic metabolism. Lemborexant, a dual orexin receptor antagonist, promotes physiological sleep by inhibiting orexin-mediated wakefulness pathways. This study aims to evaluate the efficacy and safety of lemborexant for improving sleep in patients with liver cirrhosis.

Detailed description

Patients with liver cirrhosis frequently experience sleep-wake disturbances such as insomnia, delayed sleep onset, or fragmented sleep. These disturbances may contribute to neurocognitive dysfunction and precipitate hepatic encephalopathy. However, conventional hypnotics such as benzodiazepines may worsen encephalopathy and are generally avoided. Lemborexant selectively antagonizes orexin receptors OX1R and OX2R, modulating sleep without profound respiratory suppression or GABAergic effects. This randomized, three-armed, double-blind placebo-controlled trial aims to determine whether lemborexant improves sleep quality in patients with cirrhosis while maintaining acceptable neurocognitive and safety outcomes.

Interventions

DRUGLemborexant

Lemborexant 5 mg orally once nightly before bedtime/ Lemborexant 10 mg orally once nightly before bedtime,

DRUGPlacebo

Matching placebo taken orally once nightly before bedtime.

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* adults aged 18 years or older; * willingness to participate in the clinical trial as evidenced by written informed consent; documented diagnosis of liver cirrhosis in the medical record, with disease severity assessed using the Child-Pugh score and supported by imaging findings consistent with cirrhosis on FibroScan or ultrasonography; * presence of sleep disturbance defined by a Pittsburgh Sleep Quality Index (PSQI) score greater than 5; * patients receiving inpatient or outpatient care at Cipto Mangunkusumo National General Hospital; * ability to take oral medication; * willingness of the patient or caregiver to maintain a sleep diary throughout the study period; * ability of the patient or caregiver to comply with the clinical trial protocol and complete scheduled serial assessments.

Exclusion criteria

* advanced liver cirrhosis defined as Child-Pugh class C; * current use of medications with significant interactions affecting the metabolism of Lemborexant, including itraconazole, clarithromycin, fluconazole, verapamil, tramadol, rifampicin, carbamazepine, bosentan, efavirenz, etravirine, and modafinil; * ongoing alcohol consumption or intake of grapefruit juice during the study period; * pregnancy, breastfeeding, or plans to become pregnant during the study; * presence of significant comorbid conditions such as autoimmune disease, * stage V chronic kidney disease, HIV/AIDS, or known or suspected hypersensitivity to the investigational drug; * concurrent participation in another clinical trial at the time of screening.

Design outcomes

Primary

Measure	Time frame	Description
Sleep quality	From enrollment to the end of treatment at 2 weeks	PSQI score

Secondary

Measure	Time frame	Description
Hepatic Encephalopathy - Stroop Test	From enrollment to the end of treatment at 2 weeks	Stroop Test Score
Liver function tests	From enrollment to the end of treatment at 2 weeks	Liver function tests including ALT, AST, and total bilirubin levels
Persistence of effects (sleep quality)	PSQI changes post-crossover at week 2 - week 4	PSQI score

Countries

Indonesia

Contacts

PRINCIPAL_INVESTIGATORRino Alvani Gani, Professor, Internist, MD

Hepatobiliary Division, Internal Medicine Department, Dr Cipto Mangunkusumo National General Hospital, Faculty of Medicine Universitas Indonesia, Jakarta

STUDY_DIRECTORPitt Akbar, MD, Internist