Clinical trial NCT01244503: Prediction of Severity of Liver Disease by a 13C Octanoate Breath Test (OBT)
Official title: Prediction of Severity of Liver Disease in Patients With Suspected Nonalcoholic Fatty Liver Disease (NAFLD) by 13C Octanoate Breath Test (OBT)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Metabolic Syndrome
Nonalcoholic Fatty Liver Disease
Lead sponsor: Virginia Commonwealth University
Sponsor class: OTHER
Collaborators: name: Meridian Bioscience, Inc.
First posted: 2010-11-19
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: The purpose of the study is to demonstrate that the ¹³C-Octanoate Breath Test (OBT) can be used as an aid, in conjunction with other clinical information and medical history, for evaluating disease severity and detecting NASH with a high probability.

Detailed description: The OBT was chosen to assess, along with other parameters, liver health in subjects suspected of NAFLD (non alcoholic fatty liver disease).

Octanoate is absorbed promptly from the intestinal lumen and transported rapidly to the liver through the portal venous system, enters the hepatic mitochondria independently of the carnitine transport system and undergoes hepatic mitochondrial beta-oxidation which produces acetyl coenzyme A (CoA). Finally, acetyl CoA enters the Krebs cycle and is oxidized by carbon dioxide (CO2). This is a non invasive test that can be performed routinely at every visit to assess disease severity. The subject is connected to a breath analyzer via a nasal cannula for approximately 1 hour, that measures baseline breath and changes in delta over baseline due to metabolization of Octanoate.

Eligibility criteria: Inclusion Criteria:

* Adult men or women (\>18 years of age)
* • Liver -biopsy ( at least 1.7 cm and 4 portal tracts) performed within 6 months of breath test or planned within the next 6 weeks, providing no treatment for liver disease was given between the biopsy and the OBT Any elevation of liver enzymes above the upper limit of normal (any or all of the following: AST,ALT, GGT, Alkaline phosphatase)
* At least one of the features of the metabolic syndrome

  * waist circumference \> 100 cm for men, 88 cm for women
  * triglycerides \> 150 mg/dl
  * fasting blood sugar \> 110 mg/dl
  * HDL cholesterol \< 40 mg/dl
  * blood pressure \> 130/85 mm Hg
* No other known co-existent liver disease, excluded by appropriate serologic testing

Exclusion Criteria:

* Positive studies for any of the following:
* hepatitis C (PCR)
* hepatitis B (surface antigen or DNA)
* iron saturation \> 60% + gene test for hereditary hemochromatosis
* antinuclear antibody at a titer \> 1: 160 along with hypergammaglobulinemia and ALT levels\>250 U/L

  * Patient has Alpha-1-antitrypsin level below lower limit of normal (\< 150 mg/dl)
  * Patient has alcohol consumption \> 20 gm/day for women and \> 30 gm/day for men
  * Patient is pregnant
  * Patient has been taking known hepatotoxic drugs e.g. (e.g.acebutolol, indomethacin,phenylbutazone,allopurinol,isoniazid,phenytoin,atenolol,ketoconazole,piroxicam,carbamazepine,labetalol,probenecid,cimetidine,maprotiline,pyrazinamide,dantrolene, metoprolol,quinidine,diclofenac, mianserin)• Patients that have had more than 10% reduction in body weight since biopsy
  * Patient with known severe congestive heart failure (LVEF on echocardiogram \< 20%)
  * Patient with known severe pulmonary hypertension (By echocardiogram, PAS \>45 mmHg)
  * Patient with uncontrolled diabetes mellitus (HA1c\>10)
  * Patient with previous surgical bypass surgery
  * Patient with extensive short bowel syndrome(\>100 cm)
  * Patient currently receiving total parenteral nutrition
  * Patient is a recipients of any organ transplant
  * Patients that received any anti-viral treatment or any other liver therapy between the time of the biopsy and the breath test.
  * Women who are pregnant
  * Patients with an acute current exacerbation of chronic obstructive pulmonary disease or bronchial asthma.
  * Patient has taken drugs that can interfere with octanoate metabolism or can also cause NAFLD independent of the metabolic syndrome, including: corticosteroids, amiodarone, tetracycline, valproic acid, methotrexate, stavudine, zidovudine.
  * Patients unable or refuse to sign informed consent
  * Patients that based on the opinion of the investigator should not be enrolled into this study
  * Patients that are participating in other clinical trials evaluating experimental treatments or procedures

Primary outcomes:
measure: The Peak Value of the PDR (Percentage Dose Recovery of 13C) of OBT (Octanoate Breath Test)
timeFrame: 1 hour
Secondary outcomes:
measure: Histology -NAS Scoring of Liver Biopsy
timeFrame: Up to 6 months
Other outcomes:
Locations:
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
Study officials:
affiliation: Virginia Commonwealth University
name: Arun J. Sanyal, M.D.
role: PRINCIPAL_INVESTIGATOR
References: