The effect of induced hyperammonaemia on sleep and melanopsin-mediated pupillary light response in patients with liver cirrhosis: A single-blinded randomized crossover trial

PLoS One. 2022 Sep 28;17(9):e0275067. doi: 10.1371/journal.pone.0275067. eCollection 2022.

Abstract

Background & aims: Sleep disturbances are related to hepatic encephalopathy and hyperammonaemia in patients with cirrhosis. The circadian rhythm is regulated by light stimulation of the retina via melanopsin-containing ganglion cells. The study aimed to investigate whether induced hyperammonaemia affects the pupillary light response and sleep efficiency in patients with cirrhosis.

Methods: The study was a single-blinded crossover trial including nine patients with cirrhosis. Sleep was evaluated by Pittsburgh Sleep Quality Index (PSQI) and monitored for twelve nights with wrist accelerometers and sleep diaries. On two experimental days, separated by one week, patients were randomized to ingest either an oral amino acid challenge (AAC) or an isocaloric glucose solution (GS). We measured pupillary light response, capillary ammonia, the Karolinska Sleepiness Scale (KSS), and two neuropsychological tests on both experimental days.

Results: The patients had poor self-assessed sleep quality. The amino acid challenge led to a significant increase in capillary ammonia and KSS. The time spent in bed sleeping after AAC was longer and with a reduced movement index compared to baseline but not different from GS. We found no difference in the pupillary light response or neuropsychiatric tests when comparing the effect of AAC with GS.

Conclusions: Patients with cirrhosis had impaired sleep quality. Induced hyperammonaemia led to increased sleepiness but had no acute effect on pupillary light response or the neuropsychiatric tests.

Trial registration: Registration number: NCT04771104.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids
  • Ammonia
  • Circadian Rhythm
  • Cross-Over Studies
  • Glucose
  • Humans
  • Hyperammonemia*
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / psychology
  • Rod Opsins
  • Sleep / physiology
  • Sleepiness

Substances

  • Amino Acids
  • Rod Opsins
  • melanopsin
  • Ammonia
  • Glucose

Associated data

  • ClinicalTrials.gov/NCT04771104

Grants and funding

Anna Emilie Kann was supported by a pre-graduate scholarship from the Novo Nordisk Foundation (NNF16OC0020490). The funder had no role in study design, data collection, analysis, manuscript preparation, or decision to publish. No additional funders, either internally or externally.