Hepatic Encephalopathy and Albumin Lasting Cognitive Improvement

Last updated: February 10, 2025
Sponsor: Hunter Holmes Mcguire Veteran Affairs Medical Center
Overall Status: Active - Recruiting

Phase

2

Condition

Arginase Deficiency

Liver Disease

Hepatic Encephalopathy

Treatment

Albumin

Albumin Infusion

Clinical Study ID

NCT06052176
BAJAJ0035
  • Ages > 18
  • All Genders

Study Summary

Hypothesis: Improvement in cognitive dysfunction with IV albumin in patients with cirrhosis with prior HE and MHE lasts for several weeks after albumin infusion has ended, and is due to persistent improvement in inflammatory markers, endothelial dysfunction, albumin function and gut microbial changes.

This will be a single-arm, single-blind sequential trial of IV 25% albumin and IV saline over 8 weeks with biological sampling and cognitive and health related quality of life (HRQOL) testing with each subject acting as their own control.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Age >18 years

  • Cirrhosis diagnosed using either (a) liver biopsy, (b) transient wave elastography (>20 KPa) (c) radiological evidence consistent with cirrhosis, (d) in a patient withchronic liver disease endoscopic or radiological evidence of varices (e), in apatient with chronic liver disease, platelet count <150,000/mm3 and AST/ALT ratio >1.

  • Cognitive impairment defined by MHE on psychometric hepatic encephalopathy score (PHES), critical flicker frequency (CFF), or EncephalApp Stroop

  • Prior HE controlled by lactulose or rifaximin for at least one month

  • Serum albumin <4gm/dl

Exclusion

Exclusion Criteria:

  • Unclear diagnosis of cirrhosis

  • No prior overt HE

  • No cognitive impairment on the tests noted

  • Requiring regular albumin infusions within 3 months or anticipated during the studyvisit

  • Infection within a month

  • Allergies to albumin

  • Unlikely to be adherent to the study

  • Unable or unwilling to consent

  • West Haven Criteria>2

  • Alcohol abuse within 1 month

  • Serum albumin >4gm/dl

  • Congestive heart failure

Study Design

Total Participants: 30
Treatment Group(s): 2
Primary Treatment: Albumin
Phase: 2
Study Start date:
November 02, 2023
Estimated Completion Date:
October 01, 2026

Study Description

In outpatients with cirrhosis with prior HE who have cognitive impairment despite adequate therapy, how long the impact of albumin lasts and through which potential mechanism(s) needs to be determined.

A prior recent HEAL trial showed that patients with prior HE and current minimal hepatic encephalopathy (MHE) randomized to albumin experienced significant improvement in cognitive dysfunction and psychosocial quality of life. Moreover, these improvements persisted a week after the last albumin infusion, which was not seen in the placebo group. This was accompanied by an improvement in endothelial dysfunction, ischemia-modified albumin levels and inflammatory markers that persisted one week even after albumin discontinuation. The reported half-life of IV albumin is 2 weeks, but the function and the length of time of albumin's action in decompensated cirrhosis is lower, and further details surrounding albumin pharmacokinetics in this population remain unelucidated. The mechanisms and length of time albumin's potential improvement for patients with MHE after treatment discontinuation also require continued study.

Study design:

This will be a single-arm, single-blind sequential trial of IV 25% albumin and IV saline over 8 weeks with biological sampling and cognitive and health related quality of life (HRQOL) testing with each subject acting as their own control.

Th order of the albumin and placebo infusion and blind the infusions from the subjects and the assessors of the outcomes will be changed.

Connect with a study center

  • Hunter Holmes McGuire VA Medical Center

    Richmond, Virginia 23249
    United States

    Active - Recruiting

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