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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
Meridian Bioscience, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Non-Alcoholic Steatohepatitis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Adult men or women (≥18 years of age)
  2. 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)
  3. 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
  4. No other known co-existent liver disease, excluded by appropriate serologic / other testing
  5. Imaging - US / CT / MRI (if available) with the typical image of Fatty Liver or suggestive of NASH.
  6. Patient (or legal guardian) able and willing to sign an Informed Consent Form
  7. Can tolerate an overnight (8-hour) fast

Exclusion Criteria:

  1. Positive studies for any of the following within three years prior to biopsy:

    1. Anti HCV positive
    2. Anti HB core antibody positive
    3. Iron saturation > 60% + gene test for hereditary hemochromatosis or iron overload as defined by presence of 3+ or 4+ stainable iron on liver biopsy
    4. Antinuclear antibody at a titer > 1: 160 along with hypergammaglobulinemia and 5 times ALT normal levels
    5. Alpha-1-antitrypsin level below lower limit of normal (< 150 mg/dl) or no PAS diastase resistant globules on biopsy.
    6. 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
    7. Low level of ceruloplasmin
    8. Drug-induced liver disease as defined on the basis of typical exposure and history
  2. Patients known to have chronic liver disease other than NAFLD as routinely diagnosed by the investigator
  3. Concurrent acute hepatic condition other than NAFLD
  4. Alcohol consumption > 20 gm/day (0.71 oz/day) for women and > 30 gm/day (1.06 oz/day) for men
  5. 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
  6. 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
  7. Patients that have had more than 10% weight change between biopsy and enrollment.
  8. Hypersensitivity to any of the study substrates; i.e. Octanoate or Methacetin respectively
  9. 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%)
  10. Previous surgical GI bypass surgery
  11. Extensive small bowel resection (>100 cm)
  12. Known uncontrolled malabsorption or diarrhea
  13. Concurrent total parenteral nutrition
  14. Any organ transplant
  15. 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
  16. Pregnant or breast feeding
  17. Patients and/or legal guardian unable or refusing to sign informed consent
  18. Patients that, based on the opinion of the investigator, should not be enrolled into this study due to safety / adherence reasons.
  19. Patients participating in other clinical trials and already receiving experimental treatments or procedures
  20. Patients with suspected or documented hepatocellular carcinoma by ultra-sound or other imaging modality
  21. 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

First Posted
December 4, 2014
Last Updated
December 19, 2022
Sponsor
Meridian Bioscience, Inc.
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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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