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

Primary Purpose

Metabolic Syndrome, Nonalcoholic Fatty Liver Disease

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Sodium Octanoate Breath Test

About this trial

This is an interventional diagnostic trial for Metabolic Syndrome

Eligibility Criteria

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

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

Sites / Locations

Baylor College of Medicine
Virginia Commonwealth University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Sodium Octanoate Breath Test

Arm Description

Only subjects with metabolic syndrome and suspected non alcoholic fatty liver disease will undergo breath test. They must not have any other liver disease.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

NCT ID

NCT01244503

First Posted

November 17, 2010

Last Updated

July 27, 2015

Sponsor

Virginia Commonwealth University

Collaborators

Meridian Bioscience, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT01244503

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2015

Overall Recruitment Status

Terminated

Why Stopped

Budgetary Issues

Study Start Date

February 2011 (undefined)

Primary Completion Date

May 2012 (Actual)

Study Completion Date

June 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Virginia Commonwealth University

Collaborators

Meridian Bioscience, Inc.

4. Oversight

Data Monitoring Committee

5. Study Description

Brief 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.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Metabolic Syndrome, Nonalcoholic Fatty Liver Disease

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

61 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Sodium Octanoate Breath Test

Arm Type

Experimental

Arm Description

Only subjects with metabolic syndrome and suspected non alcoholic fatty liver disease will undergo breath test. They must not have any other liver disease.

Intervention Type

Drug

Intervention Name(s)

Sodium Octanoate Breath Test

Other Intervention Name(s)

Octanaote, sodium octanoate

Intervention Description

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.

Primary Outcome Measure Information:

Title

The Peak Value of the PDR (Percentage Dose Recovery of 13C) of OBT (Octanoate Breath Test)

Description

Time Frame

1 hour

Secondary Outcome Measure Information:

Title

Histology -NAS Scoring of Liver Biopsy

Description

Time Frame

Up to 6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Arun J. Sanyal, M.D.

Organizational Affiliation

Virginia Commonwealth University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Baylor College of Medicine

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Facility Name

Virginia Commonwealth University

City

Richmond

State/Province

Virginia

ZIP/Postal Code

23298

Country

United States

12. IPD Sharing Statement

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

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