BreathID Multi-center HCV Liver Breath Test Study
The goal of this study is to validate the BreathID 13C-methacetin breath test (MBT) as a non-invasive simple-to-use metabolic test, which could be utilized to detect severe liver fibrosis (>2 in METAVIR) in patients with chronic HCV liver disease.The test is a breath-test using a free-standing device (BreathID®) that measures metabolization of a 13C-labeled substrate (13C-methacetin) in real time.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
|Official Title:||Validation of a Breath Test for Assessment of Liver Fibrosis in Patients With Chronic Hepatitis C Viral Infection|
- Correlation of Breath Test (MBT) to Fibrosis [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]13 C Lebeled substrate is metabolized by Liver and reflects liver function. It is hypothesized that this correlated to liver fibrosis
|Study Start Date:||July 2006|
|Study Completion Date:||February 2007|
|Primary Completion Date:||February 2007 (Final data collection date for primary outcome measure)|
C13 methacetin dissolved in water to be ingested after breath baseline collected. Metabolism to measured in real time.
Other: MBT and BreathID
75 mg methacetin (c13 labelled) dissolved in 150 cc water ingested and breath collected before and after ingestion.
Percutaneous liver biopsy has been utilized for decades to assess the severity of chronic HCV liver disease. 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. Several grading systems have been developed over the past 2 decades to quantify the overall severity of the liver biopsy specimen. 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 and may cause some discomfort to the patient. Percutaneous liver biopsy is associated with potential complications, including bleeding (1%-3%), pain (20%-30%), bile peritonitis (<1%), pneumothorax (<1%), punctured viscera (<1%), and death. 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.
Breath testing with 13C-labeled substrates provide a safe, non-invasive means for evaluating hepatic metabolism that is correlated with liver histology. 13C is a stable, non-radioactive isotope, which can by 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 need to be administered orally, rapidly absorbed, exclusively metabolized by the liver metabolism and 13C would be measured in exhaled breath within 20-30 minutes. Hepatic metabolism of the compound is 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 BreathID® collection system and analyzer unit.
The compound selected for this study will be 13C-methacetin. Methacetin meets all of the qualifications for an excellent substrate for liver breath tests. It is a non-toxic small molecule. 13C can be synthesized into a key location within this agent. It can be administered orally in solution. It is rapidly absorbed and metabolized by hepatic microsomes and this process releases CO2 as a by-product in exhaled breath. No reports of any complications or side effects using this substance have been reported.
13C-methacetin is rapidly absorbed and metabolized by healthy liver cells into acetaminophen and 13CO2. The resultant CO2 can be measured in the exhaled breath. The amount of metabolized methacetin indicates the capability of the liver to accomplish one of its main physiological tasks and has been shown to correlate with liver fibrosis and cirrhosis.
|United States, New York|
|Mount Sinai School of Medicine|
|New York, New York, United States, 10029-6574|
|United States, Texas|
|Baylor College of Medicine|
|Houston, Texas, United States, 77030|
|United States, Virginia|
|Virginia Commonwealth Univeristy|
|Richmond, Virginia, United States, 23284|
|U.S. Dept. of Veteran Affairs, Hunter Holmes McGuire Medical Center|
|Richmond, Virginia, United States, 23249-0001|
|Hadassah Medical Center|
|Principal Investigator:||Doug Dieterich, MD||Mount Sinai School of Medicine|
|Principal Investigator:||John M Vierling, MD||Baylor College of Medicine|
|Principal Investigator:||Mitchell Shiffman, MD||Virginia Commonwealth University|
|Principal Investigator:||Maya Margalit, MD||Hadassah Medical Center|
|Principal Investigator:||Douglas M. Heuman, M.D.||U.S. Dept. of Veteran Affairs, Hunter Holmes McGuire Medical Center|