Hepatic Encephalopathy and Albumin Lasting Cognitive Improvement (HEAL-LAST)

Hunter Holmes Mcguire Veteran Affairs Medical Center

Status and phase: Enrolling; Phase 2

Conditions: Hepatic Encephalopathy; Cirrhosis

Treatments: Drug: Albumin Infusion

Study type: Interventional

Funder types: Other U.S. Federal agency; Industry

Identifiers

NCT06052176

BAJAJ0035

Details and patient eligibility

About

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.

Full 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.

Enrollment: 30 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: Double Blind

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30 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Saline given at the same volume as the albumin on visits the patients are assigned to it

Treatment:

Drug: Albumin Infusion

Albumin

Active Comparator group

Description:

IV Albumin at 1.5g/kg ideal body weight

Treatment:

Drug: Albumin Infusion