Clinical trial NCT00244569: Development of a Breath Test for Monitoring Patients With Liver Disease
Official title: Development of a Breath Test for Monitoring Liver Metabolic Function in Patients With Chronic Liver Disease and Cirrhosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Fatty Liver
Cirrhosis
Keywords: Nonalcoholic Fatty Liver Disease
Nonalcoholic Steatohepatitis
Liver Function
Metabolism
Cirrhosis
Fibrosis
Liver
Lead sponsor: Virginia Commonwealth University
Sponsor class: OTHER
Collaborators: name: Oridion
First posted: 2005-10-26
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: The purpose of this study is to determine the safety and efficacy of the Oridion Breath ID machine in monitoring liver metabolic functions.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Adult men and women (age 18+)
* Liver histology consistent with NAFLD/NASH performed within the past 24 months
* Patients with cirrhosis must have ultrasound, computed tomography (CT) scan, or magnetic resonance imaging (MRI) examination of liver performed within the previous 6 months demonstrating no evidence for hepatocellular carcinoma

Exclusion Criteria:

* Any liver disease beyond NAFLD/NASH
* Severe congestive heart failure
* Severe pulmonary hypertension
* Chronic renal insufficiency defined by a serum creatinine above normal
* Uncontrolled diabetes mellitus
* Any autoimmune disorder which is currently being treated with immune suppressive medication
* Proven or suspected hepatocellular carcinoma
* Previous surgical bypass surgery for morbid obesity
* Extensive small bowel resection
* Patients currently receiving total parenteral nutrition
* Recipients of any organ transplant
* Women who are pregnant
* Patients who, in the opinion of the investigator, should not be enrolled in this study

Primary outcomes:
measure: 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.
measure: A p value of 0.05 or less will be considered significant.
Secondary outcomes:
measure: 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.
Other outcomes:
Locations:
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
Study officials:
affiliation: Virginia Commonwealth University
name: Mitchell L. Shiffman, MD
role: PRINCIPAL_INVESTIGATOR
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