Development of a Breath Test for Monitoring Patients With Liver Disease
Device: Breath ID Machine
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
|Official Title:||Development of a Breath Test for Monitoring Liver Metabolic Function in Patients With Chronic Liver Disease and Cirrhosis|
- The mean and standards of results obtained from the Breath ID system for each of the 3 groups of patients with nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) will be compared by chi squared analysis.
- A p value of 0.05 or less will be considered significant.
- Receiver-operator curves will be developed to compare the results of the Breath ID to each histologic group of patients studied. A p value of 0.05 will be considered significant.
|Study Start Date:||September 2005|
|Study Completion Date:||April 2007|
Percutaneous liver biopsy has been utilized for decades to assess the severity of chronic liver disease, regardless of etiology. During this procedure a core sample of liver is obtained and examined histologically for the presence of inflammation, fibrosis and other features characteristic of specific liver disorders.Although liver biopsy is the gold standard by which to assess liver disease severity the procedure has significant limitations. Liver biopsy is a costly, invasive procedure with risks for morbidity and mortality. In addition, liver biopsy and examination of liver histology is subject to sampling variation and the manner by which these findings are evaluated and reported by individual pathologists.
Because of these limitations several investigators have attempted to develop alternative methods by which to assess liver disease severity. One approach was the development of serum markers which can estimate liver fibrosis. Such tests were developed by analyzing a battery of serum liver chemistries and the platelet count. Unfortunately, the test cannot detect more subtle changes in liver fibrosis and does not provide any information regarding hepatic function in patients with established cirrhosis. The concept of a metabolic liver function test, which could be utilized to assess the liver function was first explored several decades ago (20). Such tests are performed by administering a compound either orally or intravenously. The compound is removed by the liver from the blood, metabolized and a metabolic product is released back into the blood and excreted in the urine, saliva or exhaled breath; or the metabolic product is excreted in bile. Measuring the amount of the administered product that remains in serum over time or the amount of metabolic product which is produced and/or the rate at which this product is excreted provides an accurate measure of hepatic metabolic function.
Breath testing utilizing 13C labeled substrates provides a safe, non-invasive means for measuring hepatic metabolism. 13C is a stable, non-radioactive isotope which can be incorporated into a specific location within a test substrate so that it would be released when the compound is metabolized by the liver. Ideally, the 13C-compound would be administered orally, rapidly absorbed, metabolized by the liver and 13CO2 would be measured in exhaled breath within 20-30 minutes. Hepatic metabolism of the compound would be assessed by measuring the ratio of 13C/12C in exhaled breath. The ability to detect, differentiate and quantify 13C and 12C in exhaled CO2 has been greatly facilitated by the recent development of the Breath ID® collection system and analyzer unit. This portable device continuously senses exhaled breath and analyzes CO2 in real-time through a nasal cannula worn by the patient.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00244569
|United States, Virginia|
|Virginia Commonwealth University|
|Richmond, Virginia, United States, 23298|
|Principal Investigator:||Mitchell L. Shiffman, MD||Virginia Commonwealth University|