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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02314026
Recruitment Status : Completed
First Posted : December 10, 2014
Results First Posted : March 19, 2019
Last Update Posted : March 19, 2019
Information provided by (Responsible Party):
Exalenz Bioscience LTD.

Tracking Information
First Submitted Date  ICMJE December 4, 2014
First Posted Date  ICMJE December 10, 2014
Results First Submitted Date  ICMJE February 7, 2019
Results First Posted Date  ICMJE March 19, 2019
Last Update Posted Date March 19, 2019
Actual Study Start Date  ICMJE March 2015
Actual Primary Completion Date June 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 27, 2019)
  • Number of Participants With Biopsy Proven Non-Alcoholic Steatohepatitis [ Time Frame: 30 days ]
    Non-Alcoholic Steatohepatitis (NASH) as determined by liver biopsy histology will be the comparator
  • Liver Decompensation as Measured by Area Under Receiver Operating Curve [ Time Frame: 36 months ]
    Observe if breath tests correlate to clinical outcome of liver decompensation, including ascites, variceal bleeding, hepatic encephalopathy and spontaneous bacterial peritonitis.
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures
 (submitted: February 27, 2019)
Number of Participants With Adverse Events [ Time Frame: 48 hours from last breath test ]
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.
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE BREATHID Octanoate Breath Test With or Without Methacetin Breath Test for Correlation With Biopsy in NASH
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Condition  ICMJE Non-Alcoholic Steatohepatitis
Intervention  ICMJE
  • Device: Suspected NASH BreathID test with 13C-Octanoate
    Subject will have breath measured before and after ingestion of solution of 100 mg 13C Octanoate dissolved in 150 cc of water
    Other Name: Sodium Octanoate breath test
  • Device: Suspected NASH Breath test with 13C Methacetin
    Subject will have breath measured before and after ingestion of solution of 75 mg 13C Methacetin dissolved in 150 cc of water
Study Arms  ICMJE Experimental: Suspected NASH
13C-Octanoate, 13C-Methacetin
  • Device: Suspected NASH BreathID test with 13C-Octanoate
  • Device: Suspected NASH Breath test with 13C Methacetin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 11, 2017)
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE June 2017
Actual Primary Completion Date June 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   France,   United Kingdom,   United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT02314026
Other Study ID Numbers  ICMJE NASH-EX-1114
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Exalenz Bioscience LTD.
Study Sponsor  ICMJE Exalenz Bioscience LTD.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Yaron Ilan, M.D. Hadassah Medical Organization
PRS Account Exalenz Bioscience LTD.
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP