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BARI: Biomarkers of Liver Pathology in Patients With Presumed Non-Alcoholic Steatohepatitis Following Bariatric Surgery

Sponsor
AdventHealth Translational Research Institute (Other)
Overall Status
Completed
CT.gov ID
NCT03294850
Collaborator
(none)
14
Enrollment
1
Location
2
Arms
25.8
Actual Duration (Months)
0.5
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate imaging and other biomarkers of non-alcoholic fatty liver disease before and after bariatric surgery.

Condition or Disease Intervention/Treatment Phase
  • Procedure: Bariatric surgery
  • Device: HepQuant SHUNT Dual Cholate Liver Diagnostic Kit
 N/A

Study Design

Study Type:
Interventional
Actual Enrollment :
14 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Basic Science
Official Title:
Evaluation of Biomarkers to Quantify Liver Pathology in Patients With Presumed Non-Alcoholic Steatohepatitis at Baseline and Following Bariatric Surgery (BARI)
Actual Study Start Date :
Jul 18, 2018
Actual Primary Completion Date :
Nov 14, 2019
Actual Study Completion Date :
Sep 11, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: NASH group

These are individuals that have been identified as having NASH by MRE. Confirmation with liver biopsy required for continuation in the longitudinal study.

Procedure: Bariatric surgery
Subjects enrolling in the study who are undergoing bariatric surgery as part of their medical care will be studied

Device: HepQuant SHUNT Dual Cholate Liver Diagnostic Kit
For the experimental group, the device will be used to monitor the effect of bariatric surgery on liver function. For the active comparator group, the device will be used for the assessment of baseline liver function.
Active Comparator: Non-NASH (NAFLD or normal) group

These are individuals that do not have NASH. They either have normal liver physiology or only have evidence of hepatic steatosis. This group will be studied up until the day of their bariatric surgery and will serve as a comparator population with respect to baseline measurements.

Procedure: Bariatric surgery
Subjects enrolling in the study who are undergoing bariatric surgery as part of their medical care will be studied

Device: HepQuant SHUNT Dual Cholate Liver Diagnostic Kit
For the experimental group, the device will be used to monitor the effect of bariatric surgery on liver function. For the active comparator group, the device will be used for the assessment of baseline liver function.

Outcome Measures

Primary Outcome Measures

  1. Percent Change in Liver Fat Between Baseline and 12 Weeks Post-surgery [12 weeks]

    Assessed by magnetic resonance imaging proton density fat fraction (MRI PDFF)

  2. Percent Change in Liver Stiffness Between Baseline and12 Weeks Post-surgery [12 weeks]

    We will evaluate change in liver stiffness, a surrogate for fibrosis, as assessed by magnetic resonance elastography (MRE)

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:

  • Age ≥18 years

  • Undergoing bariatric surgery (Roux-en-Y or gastric sleeve only) as part of clinical care.

  • Negative human chorionic gonadotropin (hCG) level (female participants who become pregnant during the study will be withdrawn)

  • For nonalcoholic steatohepatitis (NASH) participants - FibroScan: Controlled Attenuation Parameter (CAP) 290 db/m and Vibration-Controlled Transient Elastography (VCTE) 8 kilopascal (kPa). For participants who meet FibroScan criteria, inclusion will require MRI-PDFF ≥8%; MRE: ≥2.7 kPa.

  • For NAFLD or normal participants - FibroScan: No requirement for minimum CAP level and VCTE <7 kPa. For participants that meet the FibroScan criteria- no requirement for minimum MRI-PDFF; MRE ≤ 2 kPa.

  • Histopathology assessment of liver biopsy that confirms NASH diagnosis

  • Hemoglobin A1c (HbA1c) ≤ 9.5%

  • Fasting triglycerides ≤ 400 mg/dL (4.5 mmol/L)

  • Body mass index (BMI) ≥ 35 kg/m2

  • Able to speak and understand written and spoken English

  • Understands the procedures and agrees to participate by giving written informed consent

  • Willing and able to comply with scheduled visits, laboratory tests, and other study procedures

Exclusion Criteria:

  • Participation in other studies involving investigational drug(s) within 30 days prior to Screening Visit 1

  • History of regular alcohol consumption exceeding 14 drinks/week for females or 21 drinks/week for males within the previous 6 months

  • A total score of 8 on the Alcohol Use Disorders Identification Test questionnaire (Appendix B), indicating harmful or hazardous ethanol consumption

  • A positive urine drug test for illicit drugs

  • Clinical evidence of hepatic decompensation, including, but not limited to esophageal varices, ascites, or hepatic encephalopathy

  • Evidence of other forms of chronic liver disease (including laboratory tests as assessed by a sponsor-identified laboratory, and confirmed with a single repeat, if needed): Hepatitis B virus (HBV): defined by presence of hepatitis B surface antigen (HBsAg); Hepatitis C virus (HCV): As defined by a clinical history of previous diagnosis of Hepatitis C (treated or untreated) or a positive Hepatitis C antibody (HCVAb); Known diagnosis of primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune hepatitis, or overlap syndrome; Alcoholic liver disease; Known diagnosis of hemochromatosis; Prior known drug-induced liver injury; Known or suspected hepatocellular carcinoma (HCC) or other liver cancer; History of liver transplant, current placement on a liver transplant list, or current model of end-stage liver disease (MELD) score >12; Histological presence of cirrhosis on a prior biopsy.

  • Human Immunodeficiency Virus (HIV) infection, defined as presence of HIV antibody

  • Diagnosis of type 1 diabetes mellitus

  • Any malignancy not considered cured, except basal cell carcinoma and squamous cell carcinoma of the skin (a subject is considered cured if there has been no evidence of cancer recurrence in the previous 5 years)

  • Use of drugs historically associated with non-alcoholic fatty liver disease (NAFLD) for 1 month in the previous year prior to Visit 3 (day of Surgery); examples include: amiodarone, methotrexate, systemic glucocorticoids, tetracyclines, tamoxifen, estrogens at doses greater than those used for hormone replacement, anabolic steroids, valproic acid, other known hepatotoxins

  • Subjects with history of severe claustrophobia impacting ability to perform MRI during the study without mild sedation/treatment with an anxiolytic

  • Subjects who fulfill any of the contraindications for MRI; examples include metal implants, devices, paramagnetic objects contained within the body and excessive or metal-containing tattoos

  • Unable to participate in MR assessments due to physical limitations of equipment tolerances (MRI bore size and 500-pound weight limit) based on Investigator's judgment at screening

  • Any person unable to lie still within the environment of the MRI scanner or maintain a breath hold for the required period to acquire images without mild sedation/treatment with an anxiolytic

  • Subjects with any anatomical or pathological abnormality that would either preclude or tend to confound the analysis of study data, including any clinically significant abnormal findings on the MRI obtained at Screening Visit 2.

  • Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 56 days prior to Screening Visit 1 (participants may not donate blood any time during the study, through the final study visit)

  • Known history or suspected hypersensitivity to human serum albumin, or its preparations.

  • Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or subjects who are Pfizer employees, including their family members, directly involved in the conduct of the study

Contacts and Locations

Locations

Site City State Country Postal Code
1 Translational Research Institute for Metabolism and Diabetes Orlando Florida United States 32804

Sponsors and Collaborators

  • AdventHealth Translational Research Institute

Investigators

  • Principal Investigator: Steven Smith, MD, Study Principal Investigator

Study Documents (Full-Text)

More Information

Additional Information:

Publications

Responsible Party:
AdventHealth Translational Research Institute
ClinicalTrials.gov Identifier:
NCT03294850
Other Study ID Numbers:
  • TRIMDFH 1000376
First Posted:
Sep 27, 2017
Last Update Posted:
Jul 16, 2021
Last Verified:
Jul 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
Yes
Additional relevant MeSH terms:
Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Cholic Acids

Study Results

Participant Flow

Recruitment Details Recruitment began 7/18/2018 and concluded 12/3/2019. Participants were recruited from a local bariatric surgery medical practice.
Pre-assignment Detail
Arm/Group Title NASH Group Non-NASH (NAFLD or Normal) Group
Arm/Group Description These are individuals that have been identified as having NASH by MRE. Confirmation with liver biopsy required for continuation in the longitudinal study. Bariatric surgery: Subjects enrolling in the study who are undergoing bariatric surgery as part of their medical care will be studied HepQuant SHUNT Dual Cholate Liver Diagnostic Kit: For the experimental group, the device will be used to monitor the effect of bariatric surgery on liver function. For the active comparator group, the device will be used for the assessment of baseline liver function. These are individuals that do not have NASH. They either have normal liver physiology or only have evidence of hepatic steatosis. This group will be studied up until the day of their bariatric surgery and will serve as a comparator population with respect to baseline measurements. Bariatric surgery: Subjects enrolling in the study who are undergoing bariatric surgery as part of their medical care will be studied HepQuant SHUNT Dual Cholate Liver Diagnostic Kit: For the experimental group, the device will be used to monitor the effect of bariatric surgery on liver function. For the active comparator group, the device will be used for the assessment of baseline liver function.
Period Title: Overall Study
STARTED 4 10
COMPLETED 4 10
NOT COMPLETED 0 0

Baseline Characteristics

Arm/Group Title NASH Group Non-NASH (NAFLD or Normal) Group Total
Arm/Group Description These are individuals that have been identified as having NASH by MRE. Confirmation with liver biopsy required for continuation in the longitudinal study. Bariatric surgery: Subjects enrolling in the study who are undergoing bariatric surgery as part of their medical care will be studied HepQuant SHUNT Dual Cholate Liver Diagnostic Kit: For the experimental group, the device will be used to monitor the effect of bariatric surgery on liver function. For the active comparator group, the device will be used for the assessment of baseline liver function. These are individuals that do not have NASH. They either have normal liver physiology or only have evidence of hepatic steatosis. This group will be studied up until the day of their bariatric surgery and will serve as a comparator population with respect to baseline measurements. Bariatric surgery: Subjects enrolling in the study who are undergoing bariatric surgery as part of their medical care will be studied HepQuant SHUNT Dual Cholate Liver Diagnostic Kit: For the experimental group, the device will be used to monitor the effect of bariatric surgery on liver function. For the active comparator group, the device will be used for the assessment of baseline liver function. Total of all reporting groups
Overall Participants 4 10 14
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
40.750
(6.551)
38.600
(9.119)
39.21
(8.276)
Sex: Female, Male (Count of Participants)
Female
3
75%
8
80%
11
78.6%
Male
1
25%
2
20%
3
21.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
0
0%
2
20%
2
14.3%
Not Hispanic or Latino
4
100%
8
80%
12
85.7%
Unknown or Not Reported
0
0%
0
0%
0
0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
0
0%
0
0%
0
0%
Asian
0
0%
0
0%
0
0%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
0
0%
Black or African American
0
0%
1
10%
1
7.1%
White
4
100%
7
70%
11
78.6%
More than one race
0
0%
0
0%
0
0%
Unknown or Not Reported
0
0%
2
20%
2
14.3%
Region of Enrollment (participants) [Number]
United States
4
100%
10
100%
14
100%

Outcome Measures

1. Primary Outcome
Title Percent Change in Liver Fat Between Baseline and 12 Weeks Post-surgery
Description Assessed by magnetic resonance imaging proton density fat fraction (MRI PDFF)
Time Frame 12 weeks

Outcome Measure Data

Analysis Population Description
Only the NASH group had longitudinal evaluation
Arm/Group Title NASH Group Non-NASH (NAFLD or Normal) Group
Arm/Group Description These are individuals that have been identified as having NASH by MRE. Confirmation with liver biopsy required for continuation in the longitudinal study. Bariatric surgery: Subjects enrolling in the study who are undergoing bariatric surgery as part of their medical care will be studied HepQuant SHUNT Dual Cholate Liver Diagnostic Kit: For the experimental group, the device will be used to monitor the effect of bariatric surgery on liver function. For the active comparator group, the device will be used for the assessment of baseline liver function. These are individuals that do not have NASH. They either have normal liver physiology or only have evidence of hepatic steatosis. This group will be studied up until the day of their bariatric surgery and will serve as a comparator population with respect to baseline measurements. Bariatric surgery: Subjects enrolling in the study who are undergoing bariatric surgery as part of their medical care will be studied HepQuant SHUNT Dual Cholate Liver Diagnostic Kit: For the experimental group, the device will be used to monitor the effect of bariatric surgery on liver function. For the active comparator group, the device will be used for the assessment of baseline liver function.
Measure Participants 4 0
Mean (Standard Deviation) [percent change]
-16.4
(52.9)
2. Primary Outcome
Title Percent Change in Liver Stiffness Between Baseline and12 Weeks Post-surgery
Description We will evaluate change in liver stiffness, a surrogate for fibrosis, as assessed by magnetic resonance elastography (MRE)
Time Frame 12 weeks

Outcome Measure Data

Analysis Population Description
Only NASH group had longitudinal evaluation
Arm/Group Title NASH Group Non-NASH (NAFLD or Normal) Group
Arm/Group Description These are individuals that have been identified as having NASH by MRE. Confirmation with liver biopsy required for continuation in the longitudinal study. Bariatric surgery: Subjects enrolling in the study who are undergoing bariatric surgery as part of their medical care will be studied HepQuant SHUNT Dual Cholate Liver Diagnostic Kit: For the experimental group, the device will be used to monitor the effect of bariatric surgery on liver function. For the active comparator group, the device will be used for the assessment of baseline liver function. These are individuals that do not have NASH. They either have normal liver physiology or only have evidence of hepatic steatosis. This group will be studied up until the day of their bariatric surgery and will serve as a comparator population with respect to baseline measurements. Bariatric surgery: Subjects enrolling in the study who are undergoing bariatric surgery as part of their medical care will be studied HepQuant SHUNT Dual Cholate Liver Diagnostic Kit: For the experimental group, the device will be used to monitor the effect of bariatric surgery on liver function. For the active comparator group, the device will be used for the assessment of baseline liver function.
Measure Participants 4 0
Mean (Standard Deviation) [percent change]
1.9
(10.4)

Adverse Events

Time Frame 2.22 years
Adverse Event Reporting Description
Arm/Group Title NASH Group Non-NASH (NAFLD or Normal) Group
Arm/Group Description These are individuals that have been identified as having NASH by MRE. Confirmation with liver biopsy required for continuation in the longitudinal study. Bariatric surgery: Subjects enrolling in the study who are undergoing bariatric surgery as part of their medical care will be studied HepQuant SHUNT Dual Cholate Liver Diagnostic Kit: For the experimental group, the device will be used to monitor the effect of bariatric surgery on liver function. For the active comparator group, the device will be used for the assessment of baseline liver function. These are individuals that do not have NASH. They either have normal liver physiology or only have evidence of hepatic steatosis. This group will be studied up until the day of their bariatric surgery and will serve as a comparator population with respect to baseline measurements. Bariatric surgery: Subjects enrolling in the study who are undergoing bariatric surgery as part of their medical care will be studied HepQuant SHUNT Dual Cholate Liver Diagnostic Kit: For the experimental group, the device will be used to monitor the effect of bariatric surgery on liver function. For the active comparator group, the device will be used for the assessment of baseline liver function.
All Cause Mortality
NASH Group Non-NASH (NAFLD or Normal) Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/4 (0%) 0/10 (0%)
Serious Adverse Events
NASH Group Non-NASH (NAFLD or Normal) Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/4 (0%) 0/10 (0%)
Other (Not Including Serious) Adverse Events
NASH Group Non-NASH (NAFLD or Normal) Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 2/4 (50%) 9/10 (90%)
Cardiac disorders
Tachycardia 0/4 (0%) 0 1/10 (10%) 1
Worsening Hypertension 1/4 (25%) 1 0/10 (0%) 0
Ear and labyrinth disorders
Ear Infection 0/4 (0%) 0 1/10 (10%) 1
Gastrointestinal disorders
Gas Pain 0/4 (0%) 0 1/10 (10%) 1
H. Pylori Infection 0/4 (0%) 0 1/10 (10%) 1
Inactive mild gastritis 0/4 (0%) 0 1/10 (10%) 1
Abdominal Pain 0/4 (0%) 0 1/10 (10%) 1
General disorders
Headache 1/4 (25%) 1 1/10 (10%) 1
Migraine 0/4 (0%) 0 1/10 (10%) 1
Infections and infestations
Shingles 0/4 (0%) 0 1/10 (10%) 1
Urinary Tract Infections 0/4 (0%) 0 1/10 (10%) 1
Metabolism and nutrition disorders
Vitamin D Defficiency 0/4 (0%) 0 1/10 (10%) 1
Musculoskeletal and connective tissue disorders
Bruising, tenderness 0/4 (0%) 0 1/10 (10%) 1
Lower Leg Pain 1/4 (25%) 1 0/10 (0%) 0
Right Arm Tenderness 0/4 (0%) 0 1/10 (10%) 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cyst in pituitaty 0/4 (0%) 0 1/10 (10%) 1
Nervous system disorders
Syncope 0/4 (0%) 0 1/10 (10%) 1
Respiratory, thoracic and mediastinal disorders
Pleural Effusion 0/4 (0%) 0 1/10 (10%) 1
Sinus Infection 0/4 (0%) 0 1/10 (10%) 1

Limitations/Caveats

This trial was limited by the need to close the trial prior to enrolling all participants due to extreme difficulties with recruitment. Based on our power estimates, we needed 25 people in the NASH group, and we were only able to enroll 4. Therefore, our analyses will be limited the basic plans proposed in the protocol and will likely be exploratory and hypothesis generating in nature.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/Title Dr. Karen Corbin
Organization AdventHealth Translational Research Institute
Phone (407) 303-7100
Email Karen.Corbin@AdventHealth.com
Responsible Party:
AdventHealth Translational Research Institute
ClinicalTrials.gov Identifier:
NCT03294850
Other Study ID Numbers:
  • TRIMDFH 1000376
First Posted:
Sep 27, 2017
Last Update Posted:
Jul 16, 2021
Last Verified:
Jul 1, 2021