BREATHID Octanoate Breath Test With or Without Methacetin Breath Test for Correlation With Biopsy in NASH
Primary Purpose
Non-Alcoholic Steatohepatitis
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Suspected NASH BreathID test with 13C-Octanoate
Suspected NASH Breath test with 13C Methacetin
Sponsored by
About this trial
This is an interventional diagnostic trial for Non-Alcoholic Steatohepatitis
Eligibility Criteria
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.
Sites / Locations
- Northwestern University, Feinberg School of Medicine
- San Antonio Military Medical Center
- Baylor College of Medicine
- Liver Associates
- Texas Liver Institute
- Mary Immaculate Hospital
- St. Mary's Hospital
- Virginia Commonwealth University
- Antwerp University Hospital (UZA)
- Hôpital Pitié Salpêtrière
- Freeman Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Suspected NASH
Arm Description
13C-Octanoate, 13C-Methacetin
Outcomes
Primary Outcome Measures
Number of Participants With Biopsy Proven Non-Alcoholic Steatohepatitis
Non-Alcoholic Steatohepatitis (NASH) as determined by liver biopsy histology will be the comparator
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.
Secondary Outcome Measures
Full Information
NCT ID
NCT02314026
First Posted
December 4, 2014
Last Updated
December 19, 2022
Sponsor
Meridian Bioscience, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT02314026
Brief Title
BREATHID Octanoate Breath Test With or Without Methacetin Breath Test for Correlation With Biopsy in NASH
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
February 2019
Overall Recruitment Status
Completed
Study Start Date
March 2015 (Actual)
Primary Completion Date
June 2017 (Actual)
Study Completion Date
June 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Meridian Bioscience, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Alcoholic Steatohepatitis
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
140 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Suspected NASH
Arm Type
Experimental
Arm Description
13C-Octanoate, 13C-Methacetin
Intervention Type
Device
Intervention Name(s)
Suspected NASH BreathID test with 13C-Octanoate
Other Intervention Name(s)
Sodium Octanoate breath test
Intervention Description
Subject will have breath measured before and after ingestion of solution of 100 mg 13C Octanoate dissolved in 150 cc of water
Intervention Type
Device
Intervention Name(s)
Suspected NASH Breath test with 13C Methacetin
Intervention Description
Subject will have breath measured before and after ingestion of solution of 75 mg 13C Methacetin dissolved in 150 cc of water
Primary Outcome Measure Information:
Title
Number of Participants With Biopsy Proven Non-Alcoholic Steatohepatitis
Description
Non-Alcoholic Steatohepatitis (NASH) as determined by liver biopsy histology will be the comparator
Time Frame
30 days
Title
Liver Decompensation as Measured by Area Under Receiver Operating Curve
Description
Observe if breath tests correlate to clinical outcome of liver decompensation, including ascites, variceal bleeding, hepatic encephalopathy and spontaneous bacterial peritonitis.
Time Frame
36 months
Other Pre-specified Outcome Measures:
Title
Number of Participants With Adverse Events
Description
A phone call will be made to each subject 48 hours after the last breath test to confirm that no adverse events related to breath test have been experienced.
Time Frame
48 hours from last breath test
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yaron Ilan, M.D.
Organizational Affiliation
Hadassah Medical Organization
Official's Role
Study Director
Facility Information:
Facility Name
Northwestern University, Feinberg School of Medicine
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
San Antonio Military Medical Center
City
Forts Sam Houston
State/Province
Texas
ZIP/Postal Code
78234
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Liver Associates
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Texas Liver Institute
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78215
Country
United States
Facility Name
Mary Immaculate Hospital
City
Newport News
State/Province
Virginia
ZIP/Postal Code
23602
Country
United States
Facility Name
St. Mary's Hospital
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23226
Country
United States
Facility Name
Virginia Commonwealth University
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Facility Name
Antwerp University Hospital (UZA)
City
Edegem
ZIP/Postal Code
B-2650
Country
Belgium
Facility Name
Hôpital Pitié Salpêtrière
City
Paris
ZIP/Postal Code
75013
Country
France
Facility Name
Freeman Hospital
City
New Castle
ZIP/Postal Code
NE7 7DN
Country
United Kingdom
12. IPD Sharing Statement
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BREATHID Octanoate Breath Test With or Without Methacetin Breath Test for Correlation With Biopsy in NASH
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