Hepatic Encephalopathy and Albumin Lasting Cognitive Improvement
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Albumin Infusion.
- Who it may be relevant to
- Registry conditions: Cirrhosis, Hepatic Encephalopathy. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
Randomized Clinical Trial in Hepatic Encephalopathy to Study Lasting Cognitive Improvement With Intravenous Albumin
Overview
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.
Interventions
- Drug Albumin Infusion
Intravenous human serum albumin to be given at 1.5g/kg ideal body weight
Primary outcome measures
- Delta change in Psychometric Hepatic Encephalopathy Score (PHES) in Placebo phase vs Albumin phase [Time frame: 4 weeks each]
Secondary outcome measures (12)
- EncephalApp Stroop change in Placebo phase vs Albumin phase [Time frame: 4 weeks each]
- Critical Flicker Frequency change in Placebo phase vs Albumin phase [Time frame: 4 weeks each]
- Change in Sickness Impact Profile Placebo phase vs Albumin phase [Time frame: 4 weeks each]
- Change in PROMIS-29 Placebo phase vs Albumin phase [Time frame: 4 weeks each]
- Change in MELD-Na score Placebo phase vs Albumin phase [Time frame: 4 weeks each]
- Change in endotoxin binding protein Placebo phase vs Albumin phase [Time frame: 4 weeks each]
- Change in oxidized albumin Placebo phase vs Albumin phase [Time frame: 4 weeks each]
- Change in ischemia modified albumin Placebo phase vs Albumin phase [Time frame: 4 weeks each]
- Change in stool bile acids Placebo phase vs Albumin phase [Time frame: 4 weeks each]
- Change in serum bile acids Placebo phase vs Albumin phase [Time frame: 4 weeks each]
- Change in serum Short-chain fatty acids Placebo phase vs Albumin phase [Time frame: 4 weeks each]
- Change in stool Short-chain fatty acids Placebo phase vs Albumin phase [Time frame: 4 weeks each]
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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Non-randomized
- Model
- Sequential
- Masking
- Double blind
- Primary purpose
- Prevention
Study locations
United States · 1 center
- Hunter Holmes McGuire VA Medical Center — Richmond
Identifiers
NCT: NCT06052176 · BAJAJ0035