- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03214796
Effect of Albumin Infusion on Oxidative Albumin Modification, Albumin Binding Capacity and Plasma Thiol Status (ALB-INFUS)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Albumin infusion has been shown to improve outcome in spontaneous bacterial peritonitis, to reverse hepatorenal syndrome combined with vasoconstrictors, and to prevent post-paracentesis circulatory dysfunction. These beneficial effects are associated with hemodynamic improvement reflected by neurohumoral changes such as a decrease in plasma renin activity .
Albumin is a multifunctional protein. Its biological functions include maintenance of oncotic pressure, solubilization and transport of hydrophobic substances, antioxidant function via its free sulfhydryl group at cysteine-34, metal binding at its N-terminus, immunomodulation and/or endothelial stabilization via binding and inactivation of endotoxin. Thus the beneficial effects of albumin infusion described above are probably not only due to plasma volume expansion but also to an improvement of various aspects of albumin function.
Albumin harbours two specific binding sites described by Sudlow: site I which binds large heterocyclic compounds and dicarboxylic acids (such as bilirubin) and site II which binds aromatic carboxylic compounds (such as benzodiazepines). Decreased binding of dansylsarcosine (DS) - a model ligand for the benzodiazepin binding site II - was found in patients with end-stage liver disease. Interestingly, extracorporeal albumin dialysis using the molecular adsorbents recirculating system (MARS) has been found to improve DS binding, while no such data exist for albumin infusion under the above-mentioned conditions.
Further examples for impaired albumin function in cirrhosis include alterations in fatty acid binding (as estimated by electron paramagnetic resonance) and impaired metal binding (measured as ischemia-modified albumin).
Impaired albumin function may be caused by oxidative albumin damage, which has been found in several disease conditions including chronic liver failure. Three fractions of albumin can be discerned according to the redox state of cysteine-34: non-oxidized human mercaptalbumin (HMA) with Cys-34 as free sulfhydryl, reversibly oxidized human nonmercaptalbumin-1 (HNA1) with Cys-34 as mixed disulfide, and irreversibly oxidized human nonmercaptalbumin-2 (HNA2) with Cys-34 oxidized to sulfenic, sulfinic or sulfonic acid. The investigators of this study have previously reported marked oxidative albumin damage in decompensated cirrhosis and even more so in acute-on-chronic liver failure and these alterations were found to be related to prognosis.
Small thiol compounds such as cysteine/cystin or glutathion interacting with the sulfhydryl group at Cys-34 may change the oxidation state of albumin and may be oxidized/reduced themselves. The role of small thiol compounds in various disease conditions and their putative alterations following albumin infusion is currently unknown. Due to the complex logistics of blood sample handling plasma thiol status is measured in a subset of 10 patients only.
While free Cys-34 of albumin accounts for about 80% of the antioxidant capacity of human plasma, both reversible and irreversible oxidation at this site will markedly reduce the antioxidant function of albumin. Besides, irreversibly oxidized albumin causes intense modifications of albumin structure and leads to marked alterations of albumin binding function.
Interestingly, oxidative albumin modification observed in chronic liver failure was paralleled by an impairment of albumin binding capacity as measured by DS binding. This finding among others has led to the concept of effective albumin concentration, which may further aggravate hypoalbuminemia observed in chronic liver failure.
The effect of albumin infusion on oxidative albumin modification and albumin function in chronic liver failure is currently unknown.
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Locations
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-
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Graz, Austria, 8010
- Department of Internal Medicine, Medical University of Graz
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- Age >18 years
- Routine indication for albumin infusion
- Informed consent
Exclusion Criteria:
- Malignant ascites
- Presence of hepatocellular carcinoma or advanced extrahepatic neoplasia
- Nephrotic syndrome
- Pregnancy, lactation
- Albumin infusion >80g within the last 48 hours
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Albumin infusion
Patients with decompensated cirrhosis and an indication for routine human albumin infusion
|
Infusion of human albumin
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Albumin oxidation status
Time Frame: 48 hours
|
changes in albumin oxidation status (HMA, HNA1, HNA2; percentage) due to albumin infusion measured by HPLC
|
48 hours
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
albumin binding capacity for dansylsarcosine
Time Frame: 48 hours
|
changes in albumin binding capacity (IC50) due to albumin infusion
|
48 hours
|
Plasma renin activity
Time Frame: 48 h
|
changes in plasma renin activity (ELISA; uU/ml) due to albumin infusion
|
48 h
|
Plasma copeptin concentration
Time Frame: 48 h
|
changes in plasma copeptin concentration (ELISA; pmol/l) due to albumin infusion
|
48 h
|
Plasma thiol status
Time Frame: 48 h
|
changes in plasma thiol status (HPLC, umol/l) due to albumin infusion
|
48 h
|
serum endotoxin levels
Time Frame: 48 h
|
changes in serum endotoxin levels (measured by HEK blue LPS detection kit, IU/ml) due to albumin infusion
|
48 h
|
Neutrophil phagocytic capacity
Time Frame: 48 h
|
changes in neutrophil phagocytic capacity (flow cytometry; percentage FITC positive cells) due to albumin infusion
|
48 h
|
Neutrophil oxidative burst
Time Frame: 48 h
|
changes in neutrophil oxidative burst (flow cytometry; percentage FITC positive cells) due to albumin infusion
|
48 h
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Rudofl E Stauber, MD, Medical University of Graz
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- ALB-INFUS
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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