Clinical trial NCT06052176: Hepatic Encephalopathy and Albumin Lasting Cognitive Improvement
Official title: Randomized Clinical Trial in Hepatic Encephalopathy to Study Lasting Cognitive Improvement With Intravenous Albumin
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Cirrhosis
Hepatic Encephalopathy
Keywords: albumin
cirrhosis
inflammation
cognitive performance
Lead sponsor: Hunter Holmes Mcguire Veteran Affairs Medical Center
Sponsor class: FED
Collaborators: name: Grifols Biologicals, LLC
First posted: 2023-09-25
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: PREVENTION

Brief 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.

Detailed 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.

Eligibility criteria: 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 with chronic liver disease endoscopic or radiological evidence of varices (e), in a patient 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 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 study visit
* 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

Primary outcomes:
measure: Delta change in Psychometric Hepatic Encephalopathy Score (PHES) in Placebo phase vs Albumin phase
timeFrame: 4 weeks each
Secondary outcomes:
measure: EncephalApp Stroop change in Placebo phase vs Albumin phase
timeFrame: 4 weeks each
measure: Critical Flicker Frequency change in Placebo phase vs Albumin phase
timeFrame: 4 weeks each
measure: Change in Sickness Impact Profile Placebo phase vs Albumin phase
timeFrame: 4 weeks each
measure: Change in PROMIS-29 Placebo phase vs Albumin phase
timeFrame: 4 weeks each
measure: Change in MELD-Na score Placebo phase vs Albumin phase
timeFrame: 4 weeks each
measure: Change in endotoxin binding protein Placebo phase vs Albumin phase
timeFrame: 4 weeks each
measure: Change in oxidized albumin Placebo phase vs Albumin phase
timeFrame: 4 weeks each
measure: Change in ischemia modified albumin Placebo phase vs Albumin phase
timeFrame: 4 weeks each
measure: Change in stool bile acids Placebo phase vs Albumin phase
timeFrame: 4 weeks each
measure: Change in serum bile acids Placebo phase vs Albumin phase
timeFrame: 4 weeks each
measure: Change in serum Short-chain fatty acids Placebo phase vs Albumin phase
timeFrame: 4 weeks each
measure: Change in stool Short-chain fatty acids Placebo phase vs Albumin phase
timeFrame: 4 weeks each
measure: Change in stool bacterial alpha diversity Placebo phase vs Albumin phase
timeFrame: 4 weeks each
measure: Change in serum inflammatory cytokines Placebo phase vs Albumin phase
timeFrame: 4 weeks each
Other outcomes:
Locations:
city: Richmond
country: United States
facility: Hunter Holmes McGuire VA Medical Center
state: Virginia
Study officials:
References: