Clinical trial NCT01766960: Altered Drug Disposition and Biomarkers for Diagnosis of Chronic Inflammatory Liver Disease
Official title: Altered Drug Disposition and Biomarkers for Diagnosis of Chronic Inflammatory Liver Disease.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Fatty Liver
Keywords: Bile acids
Pharmacokinetics
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: University of North Carolina, Greensboro
First posted: 2013-01-11
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: One-third of the U.S. population suffers from non-alcoholic fatty liver disease (NAFLD). NAFLD is caused by diabetes and obesity, and is becoming more common. Although many people have this disease, the change in how the liver handles drugs and compounds in the body has not been studied. The purpose of this study is to investigate how advanced NAFLD changes the ability of the liver to handle both endogenous and exogenous compounds.


Eligibility criteria: Inclusion Criteria:

General:

* Man or woman between 18 and 65 years of age
* Negative pregnancy test for women of childbearing potential
* Negative urine drug screen

Healthy Subjects:

* Normal liver function tests
* Normal kidney function and lipid panel

Nonalcoholic Steatohepatitis Patients:

* Recent liver biopsy with nonalcoholic fatty liver disease activity score at least 4

Exclusion Criteria:

General:

* History of significant alcohol use (\>20 g/day) and/or illicit drug use
* Inability to abstain from alcohol for 48 prior to study
* Use of drugs associated with a clinical or histological picture consistent with fatty liver disease or NASH for more than 12 consecutive weeks in the year prior to screening; these include amiodarone, tamoxifen, methotrexate, glucocorticoids, anabolic steroids, tetracyclines, estrogens (at doses greater than those used for hormone replacement) or valproate/valproic acid
* Type 2 diabetes treated with oral agents other than metformin; these include secretagogues, thiazolidinediones, alpha-glucosidase inhibitors, exenatide and pramlintide.
* Current or recent use of bile acid sequestrants, bile acid derivatives (i.e. ursodiol) or fibric acid derivatives.
* Current use of antioxidants such as silymarin, vitamin C, glutathione, or non-prescribed complementary alternative medications (including dietary supplements, megadose vitamins, herbal preparations, and special teas) within 30 days prior to screening.
* Previous liver biopsy that demonstrated presence of cirrhosis.
* Radiologic imaging consistent with cirrhosis or portal hypertension.
* Serum creatinine of 2.0 mg/dL or greater, or on dialysis, at screening.
* History of immunologically mediated disease (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, severe psoriasis, rheumatoid arthritis) that could affect the assessment of biomarkers (bile acids or inflammation).
* History of bariatric surgery.
* BMI \> 45 kg/m\^2 at screening.
* Any known hypersensitivity to opiates, opiate antagonists, or ondansetron.

Healthy Subjects:

* Taking concomitant medications, both prescription and non-prescription (including herbal products and over-the-counter medications), other than oral contraceptives and multivitamins (women stabilized on hormonal methods of birth control will be allowed to participate)
* History or other evidence of liver disease in the opinion of the study investigators.
* BMI \> 30 kg/m\^2 at screening.

Primary outcomes:
measure: Pharmacokinetic profile of morphine and its hepatically derived metabolites.
timeFrame: 8 hours post dose
Secondary outcomes:
measure: Bile acid profile
timeFrame: Pre- and postprandially
measure: FibroScan with Controlled Attenuation Parameter (CAP) Software
timeFrame: No preparation (fasting) required-consumption of large meals prior to the Fibroscan procedure is not advised
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: North Carolina Clinical and Translational Research Center
state: North Carolina
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Alfred S Barritt, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of North Carolina, Chapel Hill
name: Kim LR Brouwer, PharmD, PhD
role: PRINCIPAL_INVESTIGATOR
References: