NASH - Nonalcoholic Steatohepatitis; NAFLD - Nonalcoholic Fatty Liver Disease
Conditions
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.
Interventions
PROCEDUREBariatric surgery
Subjects enrolling in the study who are undergoing bariatric surgery as part of their medical care will be studied
DEVICEHepQuant 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.
Sponsors
AdventHealth Translational Research Institute
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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 * Negative human chorionic gonadotropin (hCG) level (female participants who become pregnant during the study will be withdrawn) * For nonalcoholic steatohepatitis (NASH) participants - FibroScan: Controlled Attenuation Parameter (CAP) 290 db/m and Vibration-Controlled Transient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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| 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) |
Countries
United States
Participant flow
Recruitment details
Recruitment began 7/18/2018 and concluded 12/3/2019. Participants were recruited from a local bariatric surgery medical practice.
Participants by arm
| Arm | Count |
|---|---|
| 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.
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. | 4 |
| 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.
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. | 10 |
| Total | 14 |
Baseline characteristics
| Characteristic | NASH Group | Total | Non-NASH (NAFLD or Normal) Group |
|---|---|---|---|
| Age, Continuous | 40.750 years STANDARD_DEVIATION 6.551 | 39.21 years STANDARD_DEVIATION 8.276 | 38.600 years STANDARD_DEVIATION 9.119 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 12 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 4 Participants | 11 Participants | 7 Participants |
| Region of Enrollment United States | 4 participants | 14 participants | 10 participants |
| Sex: Female, Male Female | 3 Participants | 11 Participants | 8 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 10 |
| other Total, other adverse events | 2 / 4 | 9 / 10 |
| serious Total, serious adverse events | 0 / 4 | 0 / 10 |
Outcome results
Primary
Percent Change in Liver Fat Between Baseline and 12 Weeks Post-surgery
Assessed by magnetic resonance imaging proton density fat fraction (MRI PDFF)
Time frame: 12 weeks
Population: Only the NASH group had longitudinal evaluation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NASH Group | Percent Change in Liver Fat Between Baseline and 12 Weeks Post-surgery | -16.4 percent change | Standard Deviation 52.9 |
Primary
Percent Change in Liver Stiffness Between Baseline and12 Weeks Post-surgery
We will evaluate change in liver stiffness, a surrogate for fibrosis, as assessed by magnetic resonance elastography (MRE)
Time frame: 12 weeks
Population: Only NASH group had longitudinal evaluation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NASH Group | Percent Change in Liver Stiffness Between Baseline and12 Weeks Post-surgery | 1.9 percent change | Standard Deviation 10.4 |