Prediction of Severity of Liver Disease by a 13C Octanoate Breath Test (OBT)

Metabolic Syndrome Clinical Trial

Official title:

Prediction of Severity of Liver Disease in Patients With Suspected Nonalcoholic Fatty Liver Disease (NAFLD) by 13C Octanoate Breath Test (OBT)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01244503
• Other study ID #: NASH-BID-FIS-808
• Status: Terminated
• Phase: Phase 2
• First received: November 17, 2010
• Last updated: July 27, 2015
• Start date: February 2011
• Est. completion date: June 2012

Study information

• Verified date: July 2015
• Source: Virginia Commonwealth University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 61
• Est. completion date: June 2012
• Est. primary completion date: May 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases
• Metabolic Syndrome
• Metabolic Syndrome X
• Nonalcoholic Fatty Liver Disease

Intervention

Drug:
• Sodium Octanoate Breath Test
100 mg of 13-C labeled sodium octanoate (Octanoate for short) is to be dissolved in 1 cup of tap water and administered to subject after baseline breath collection is completed.

Locations

Country	Name	City	State
United States	Baylor College of Medicine	Houston	Texas
United States	Virginia Commonwealth University	Richmond	Virginia

Sponsors (2)

Lead Sponsor	Collaborator
Virginia Commonwealth University	Exalenz Bioscience LTD.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Peak Value of the PDR (Percentage Dose Recovery of 13C) of OBT (Octanoate Breath Test)	To assess the ability of the OBT to assess disease severity in patients with suspected NAFLD (non alcoholic fatty liver disease) compared to NAS (Non-alcoholic-steatohepatitis (NASH) Activity Score) scoring system, where steatosis is scaled from 0-3, lobular inflammation is scaled from 0-3 and hepatocellular ballooning is scaled from 0-2. NAS score greater or equal to 5 indicates NASH. The higher the PDR peak, the better the liver health and function.PDR units are percent per hour of 13C dose recovery and describes rate of metabolism. The PDR peak is the highest rate of metabolism the liver reaches.The total range of NAS is 0-8.	1 hour	No
Secondary	Histology -NAS Scoring of Liver Biopsy	OBT will be compared to histology (including NAS score as described above)and other parameters to develop severity score. Only subjects with biopsy from routine clinical practice will be enrolled.; NAS (Non-alcoholic-steatohepatitis (NASH) Activity Score) scoring system includes the following components: steatosis, which is scaled from 0-3, lobular inflammation, which is scaled from 0-3 and hepatocellular ballooning, which is scaled from 0-2. NAS score greater or equal to 5 indicates NASH. The range of the NAS score is from 0-8.	Up to 6 months	No