BREATHID Octanoate Breath Test With or Without Methacetin Breath Test for Correlation With Biopsy in NASH

Study Overview
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Brief Summary
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This study's aim is to develop an algorithm for the ¹³C-Octanoate Breath Test with or without the ¹³C-Methacetin Breath Test (OBT and MBT respectively) for correlation with histological findings associated with of Non-Alcoholic Steatohepatitis (NASH) and other liver diseases using the BreathID® System

Detailed Description
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Non-Alcoholic Steatohepatitis (NASH) is a growing epidemic in the western world due to the contemporary eating habits and life styles.NASH can lead to cirrhosis, hepatic carcinoma and other liver complications. There are currently some treatments available. The only definitive way of detecting NASH in patients with advanced liver disease is by liver biopsy. However, liver biopsy has disadvantages, such as sampling errors, chance of complications and does not lend itself to following up after treatment. A non-invasive test that could potentially replace biopsy and aid in NASH detection and treatment monitoring, would improve management of suspected NASH patients without the need for biopsy. This protocol will obtain the results of one or two different breath tests to provide an accurate evaluation of the liver status in patients at high risk for NASH.

Official Title
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Clinical Study of the BreathID® System to Train the Algorithm for the ¹³C-Octanoate Breath Test With or Without the ¹³C-Methacetin Breath Test (OBT and MBT Respectively) for Correlation With Histological Findings Associated With Non-Alcoholic Steatohepatitis (NASH) and Other Liver Diseases

Conditions
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Non-Alcoholic Steatohepatitis

Intervention / Treatment
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* Device: Suspected NASH BreathID test with 13C-Octanoate
* Device: Suspected NASH Breath test with 13C Methacetin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult men or women (≥18 years of age) Liver biopsy, indicating NAFLD/NASH, performed within 6 months prior to both breath tests OR undergoing liver biopsy to rule-out or confrim NAFLD/NASH. NOTE:The samples obtained meet defined quality criteria. (In Appendix II of protocol) Any elevation of liver enzymes above the upper limit of normal (any or all of the following: AST, ALT, GGT, Alkaline phosphatase) for at least 3 months No other known co-existent liver disease, excluded by appropriate serologic / other testing Imaging - US / CT / MRI (if available) with the typical image of Fatty Liver or suggestive of NASH. Patient (or legal guardian) able and willing to sign an Informed Consent Form Can tolerate an overnight (8-hour) fast Exclusion Criteria: Positive studies for any of the following within three years prior to biopsy: Anti HCV positive Anti HB core antibody positive Iron saturation > 60% + gene test for hereditary hemochromatosis or iron overload as defined by presence of 3+ or 4+ stainable iron on liver biopsy Antinuclear antibody at a titer > 1: 160 along with hypergammaglobulinemia and 5 times ALT normal levels Alpha-1-antitrypsin level below lower limit of normal (< 150 mg/dl) or no PAS diastase resistant globules on biopsy. Primary biliary cirrhosis as defined by elevation of alkaline phosphatase greater than upper limit of normal and anti-mitochondrial antibody (AMA) of greater than 1:80 and consistent liver histology Low level of ceruloplasmin Drug-induced liver disease as defined on the basis of typical exposure and history Patients known to have chronic liver disease other than NAFLD as routinely diagnosed by the investigator Concurrent acute hepatic condition other than NAFLD Alcohol consumption > 20 gm/day (0.71 oz/day) for women and > 30 gm/day (1.06 oz/day) for men Drugs that may interfere with octanoate metabolism or can also cause NAFLD independent of the metabolic syndrome, including: corticosteroids, amiodarone, tetracycline, valproic acid, methotrexate, stavudine, zidovudine When MBT is performed subject should not have taken any of the following at least 48 hours prior to the breath test: Acyclovir , allopurinol, carbamazepine, cimetidine, ciprofloxacin, daidzein, (herbal) disulfiram, echinacea, enoxacin, famotidine, fluvoxamine, methoxsalen, mexiletine, montelukast, norfloxacin, phenylpropanolamine, phenytoin, propafenone, rifampin, terbinafine, ticlopidine, thiabendazole, verapamil, zileuton or any medication that might interfere with Methacetin metabolism or might affect CYP 1A2 Patients that have had more than 10% weight change between biopsy and enrollment. Hypersensitivity to any of the study substrates; i.e. Octanoate or Methacetin respectively Known extra-hepatic diseases including but not limited to: severe congestive heart failure (NIHA>2), known severe pulmonary hypertension (>35 mmHg), history of chronic obstructive pulmonary disease or uncontrolled symptomatic bronchial asthma or uncontrolled diabetes mellitus (HA1c>9.5%) Previous surgical GI bypass surgery Extensive small bowel resection (>100 cm) Known uncontrolled malabsorption or diarrhea Concurrent total parenteral nutrition Any organ transplant Patients receiving any anti-viral treatment or any other liver directed therapy, procedure or surgery between the time of the biopsy and the breath test Pregnant or breast feeding Patients and/or legal guardian unable or refusing to sign informed consent Patients that, based on the opinion of the investigator, should not be enrolled into this study due to safety / adherence reasons. Patients participating in other clinical trials and already receiving experimental treatments or procedures Patients with suspected or documented hepatocellular carcinoma by ultra-sound or other imaging modality Patients diagnosed with partial / complete portal venous occlusion, hepatic venous occlusion, previous PHT surgery, or placement of a transjugular intrahepatic portosystemic shunt (TIPS) according to initial imaging studies.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Suspected NASH<br>13C-Octanoate, 13C-Methacetin | Device: Suspected NASH BreathID test with 13C-Octanoate<br>* Subject will have breath measured before and after ingestion of solution of 100 mg 13C Octanoate dissolved in 150 cc of water<br>* Other names: Sodium Octanoate breath test;Device: Suspected NASH Breath test with 13C Methacetin<br>* Subject will have breath measured before and after ingestion of solution of 75 mg 13C Methacetin dissolved in 150 cc of water<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Biopsy Proven Non-Alcoholic Steatohepatitis | Non-Alcoholic Steatohepatitis (NASH) as determined by liver biopsy histology will be the comparator | 30 days | 
| Liver Decompensation as Measured by Area Under Receiver Operating Curve | Observe if breath tests correlate to clinical outcome of liver decompensation, including ascites, variceal bleeding, hepatic encephalopathy and spontaneous bacterial peritonitis. | 36 months |