BreathID Multi-center HCV Liver Breath Test Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00350714
Recruitment Status : Terminated (Due to FDA comments, protocol changed; new trial will be proposed shortly)
First Posted : July 11, 2006
Last Update Posted : June 21, 2011
Icahn School of Medicine at Mount Sinai
Baylor College of Medicine
Virginia Commonwealth University
Hadassah Medical Organization
VA Office of Research and Development
Information provided by:
Exalenz Bioscience LTD.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Hepatitis C Other: MBT and BreathID Phase 2

Detailed Description:

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 75 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : July 2006
Actual Primary Completion Date : February 2007
Actual Study Completion Date : February 2007

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: MBT
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.

Primary Outcome Measures :
  1. Correlation of Breath Test (MBT) to Fibrosis [ Time Frame: 12 months ]
    13 C Lebeled substrate is metabolized by Liver and reflects liver function. It is hypothesized that this correlated to liver fibrosis

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

i. Patients with a confirmed diagnosis of Chronic HCV only : ii. Patients for whom a liver biopsy has been performed within the last 90 days or who will undergo a liver biopsy within the time frame of the study.

Exclusion Criteria:

i. Severe congestive heart failure. ii. Severe pulmonary hypertension. iii.Chronic renal insufficiency defined by a serum creatinine above the limits of normal. iv. Uncontrolled diabetes mellitus (need definition).v.Any autoimmune disorder, which is currently being treated with prednisone or any other immune suppressive medication. vi.Proven or suspected hepatocellular carcinoma. vii. Previous surgical bypass surgery for morbid obesity viii.Extensive small bowel resection. ix.Patients currently receiving total parenteral nutrition x.Recipients of any organ transplant. xi.Other co-existent liver disease.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00350714

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
U.S. Dept. of Veteran Affairs, Hunter Holmes McGuire Medical Center
Richmond, Virginia, United States, 23249-0001
Virginia Commonwealth Univeristy
Richmond, Virginia, United States, 23284
Hadassah Medical Center
Jerusalem, Israel
Sponsors and Collaborators
Exalenz Bioscience LTD.
Icahn School of Medicine at Mount Sinai
Baylor College of Medicine
Virginia Commonwealth University
Hadassah Medical Organization
VA Office of Research and Development
Principal Investigator: Doug Dieterich, MD Icahn School of Medicine at Mount Sinai
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

Additional Information:
Publications of Results:
O. Goetze; N. Selzner; A. Grau; M. Fried; T. Gerlach; B. Muellhaupt 13C-Methacetin Breath Test by Online Molecular Correlation Spectroscopy Compared to APRI and Liver Biopsy for the Assessment of Fibrosis in Chronic Hepatitis C , S1047. Abstarct presented at DDW 2006

Responsible Party: Dr. Scott Friedman, Mouont Sinai School of Medicine Identifier: NCT00350714     History of Changes
Other Study ID Numbers: MBVH-0706
First Posted: July 11, 2006    Key Record Dates
Last Update Posted: June 21, 2011
Last Verified: June 2011

Keywords provided by Exalenz Bioscience LTD.:
HCV (Hepatitis C Virus)
MBT (Methacetin Breath Test)
Hepatitis C Virus Patients

Additional relevant MeSH terms:
Hepatitis A
Hepatitis C
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections