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| Name | Class |
|---|---|
| Grifols Biologicals, LLC | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Saline given at the same volume as the albumin on visits the patients are assigned to it |
|
| Albumin | Active Comparator | IV Albumin at 1.5g/kg ideal body weight |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Albumin Infusion | Drug | Intravenous human serum albumin to be given at 1.5g/kg ideal body weight |
|
| Measure | Description | Time Frame |
|---|---|---|
| Delta change in Psychometric Hepatic Encephalopathy Score (PHES) in Placebo phase vs Albumin phase | cognitive improvement (PHES score ranges from -15 to 5), higher is good | 4 weeks each |
| Measure | Description | Time Frame |
|---|---|---|
| EncephalApp Stroop change in Placebo phase vs Albumin phase | cognitive improvement (Stroop OffTime+OnTime in seconds will be evaluated); higher is worse | 4 weeks each |
| Critical Flicker Frequency change in Placebo phase vs Albumin phase |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jasmohan Bajaj, MD | Contact | 8046755802 | jasmohan.bajaj@vcuhealth.org |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hunter Holmes McGuire VA Medical Center | Recruiting | Richmond | Virginia | 23249 | United States |
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| ID | Term |
|---|---|
| D005355 | Fibrosis |
| D006501 | Hepatic Encephalopathy |
| D007249 | Inflammation |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D017093 | Liver Failure |
| D048550 | Hepatic Insufficiency |
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| ID | Term |
|---|---|
| D000418 | Albumins |
| ID | Term |
|---|---|
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
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Subjects will be blinded to which infusions are albumin versus placebo. All infusion tubing and bag will be covered in foil and the subjects will not be aware of the timing of the saline vs albumin infusion to maintain blinding for the patient.
cognitive improvement (Hz at which CFF is reached will be evaluated), higher is good
| 4 weeks each |
| Change in Sickness Impact Profile Placebo phase vs Albumin phase | Health-related quality of life change (SIP total, psychosocial and physical scores where a higher score indicates poor HRQOL willl be evaluated) | 4 weeks each |
| Change in PROMIS-29 Placebo phase vs Albumin phase | Health-related quality of life change (Total PROMIS-29 score will be evaluated) | 4 weeks each |
| Change in MELD-Na score Placebo phase vs Albumin phase | Liver disease severity change using MELD-Na; higher is worse | 4 weeks each |
| Change in endotoxin binding protein Placebo phase vs Albumin phase | Change in endotoxin binding protein will be recorded in the serum; higher is worse | 4 weeks each |
| Change in oxidized albumin Placebo phase vs Albumin phase | Change in oxidized albumin will be recorded in the serum ; higher is worse | 4 weeks each |
| Change in ischemia modified albumin Placebo phase vs Albumin phase | Change in ischemia modified albumin will be recorded in the serum | 4 weeks each |
| Change in stool bile acids Placebo phase vs Albumin phase | Change in stool bile acids (total, primary, secondary, conjugated/deconjugated) will be recorded | 4 weeks each |
| Change in serum bile acids Placebo phase vs Albumin phase | Change in serum bile acids (total, primary, secondary, conjugated/deconjugated) will be recorded | 4 weeks each |
| Change in serum Short-chain fatty acids Placebo phase vs Albumin phase | Change in serum Short-chain fatty acids (acetate, propionate, butyrate will be recorded | 4 weeks each |
| Change in stool Short-chain fatty acids Placebo phase vs Albumin phase | Change in stool Short-chain fatty acids (acetate, propionate, butyrate will be recorded | 4 weeks each |
| Change in stool bacterial alpha diversity Placebo phase vs Albumin phase | Change in Shannon diversity of stool bacteria | 4 weeks each |
| Change in serum inflammatory cytokines Placebo phase vs Albumin phase | Change in IL-6, TNF-α, IL-10, IL-1β in serum | 4 weeks each |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D001928 | Brain Diseases, Metabolic |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |