Altered Drug Disposition and Biomarkers for Diagnosis of Chronic Inflammatory Liver Disease

NCT ID: NCT01766960

Last Updated: 2016-03-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-11-30
• Study Completion Date: 2014-06-30

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.

Conditions

Fatty Liver

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Healthy volunteers

Subjects will be asked to fast overnight. Upon presentation, FibroScan procedure with CAP will be conducted and baseline and postprandial bile acid profile will be assessed. Then, intravenous morphine will be administered and the pharmacokinetic profile will be assessed over 8 hours.

Group Type: EXPERIMENTAL

High fat meal

Intervention Type: OTHER

A high fat breakfast will be administered to induce gall bladder emptying.

Morphine

Intervention Type: DRUG

Five milligrams of intravenous morphine will be administered.

Advanced nonalcoholic fatty liver disease patients

Subjects will be asked to fast overnight. Upon presentation, FibroScan procedure with CAP will be conducted and baseline and postprandial bile acid profile will be assessed. Then, intravenous morphine will be administered and the pharmacokinetic profile will be assessed over 8 hours.

Group Type: EXPERIMENTAL

High fat meal

Intervention Type: OTHER

A high fat breakfast will be administered to induce gall bladder emptying.

Morphine

Intervention Type: DRUG

Five milligrams of intravenous morphine will be administered.

Interventions

High fat meal

A high fat breakfast will be administered to induce gall bladder emptying.

Intervention Type: OTHER

Morphine

Five milligrams of intravenous morphine will be administered.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of North Carolina, Greensboro

OTHER

Sponsor Role: collaborator

University of North Carolina, Chapel Hill

OTHER

Sponsor Role: lead

Responsible Party

Sidney Barritt, MD

Assistant Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Alfred S Barritt, MD

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina, Chapel Hill

Kim LR Brouwer, PharmD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina, Chapel Hill

Locations

North Carolina Clinical and Translational Research Center

Chapel Hill, North Carolina, United States

Countries

United States

Other Identifiers

550KR41202

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

12-1599

Identifier Type: -

Identifier Source: org_study_id