Ursodeoxycholic Acid in Bariatric Surgery

Non-alcoholic Fatty Liver Disease Clinical Trial

Official title:

Effects of Ursodeoxycholic Acid on Hepatobiliary Detoxification/Elimination Mechanisms and Hepatic Fatty Acid/Triglyceride Metabolism in Morbidly Obese Patients.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01548079
• Other study ID #: UDCAINBS
• Status: Completed
• Phase: N/A
• First received: February 22, 2012
• Last updated: December 2, 2013
• Start date: October 2008
• Est. completion date: May 2010

Study information

• Verified date: December 2013
• Source: Sahlgrenska University Hospital, Sweden
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In an open-label trial, 20 otherwise healthy morbidly obese patients scheduled for bariatric surgery will be administered 20 mg/kg/day ursodeoxycholic acid for three weeks until the day before surgery. The maximum dose will be 3 g/day. Twenty other patients will serve as controls. Serum from days 1 and 21 will be analyzed for routine liver tests, bile acids, a complete lipid profile including FA and in addition for 7α-hydroxy-4-cholesten-3-one and fibroblast growth factor 19 (FGF-19), markers for bile acid synthesis its intestinal stimulation. For the evaluation of insulin resistance and possible pre-diabetes, plasma will be taken for the estimation of homeostasis model assessment (HOMA) index and oral glucose tolerance test (OGTT) will be performed at days 1 and 21. At surgery, a liver biopsy (0.5-1 g) and a white adipose tissue (WAT) specimen (1 cm2) will be taken and immediately frozen in liquid nitrogen for messenger ribonucleic acid (mRNA) and protein preparation for quantitative real-time polymerase chain reaction (RT-PCR) and Western analysis, respectively, histopathological Non-alcoholic fatty liver disease (NAFLD) grading, and measuring of hepatic and white adipose tissue (WAT) lipase activity. In all patients at randomization, abdominal ultrasound will be performed for the detection of NAFLD and gallstones and a blood sample will be taken for the analysis of polymorphisms of hepatic lipid synthesis, storage, fatty acid (FA) oxidation and export genes. Six month after operation, HOMA, OGTT and abdominal ultrasound will be repeated.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: May 2010
• Est. primary completion date: November 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years to 60 Years

Eligibility

Inclusion Criteria:

• BMI = 35 kg/m2

• Patients eligible to bariatric surgery

• Patients should have given their written consent to participate in this study

Exclusion Criteria:

• Chronic liver disease other than NAFLD (viral hepatitis, autoimmune liver disease, hemochromatosis, homozygous alpha1-antitrypsin deficiency and Wilson disease)

• Partial ileal bypass

• Inflammatory bowel disease

• Uncontrolled diabetes mellitus (fasting blood glucose > 6.7 mmol/L), hypothyroidism or hyperthyroidism, or other significant endocrine disease.

• A subject who is euthyroid on a stable replacement dose of thyroid hormone is acceptable provided the TSH is within normal range.

• Other serious disease

• Known hypersensitivity to ursodeoxycholic acid

• Patients who will not comply with the protocol.

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases
• Morbid Obesity
• Non-alcoholic Fatty Liver Disease
• Obesity, Morbid

Intervention

Drug:
• Ursodeoxycholic Acid (UDCA)
20mg/kg/day UDCA in three weeks

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Sahlgrenska University Hospital, Sweden

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in regulators of lipid turnover	Trial objectives are to determine whether (i) Hepatic and/or visceral white adipose tissue (WAT) lipase activity determines fatty acid (FA) release/balance from lipid triglyceride (TG) droplets and FA-mediated lipotoxicity in NAFLD; differences in hepatic and/or WAT activity could explain individual susceptibility to pure NAFL versus NASH (ii) UDCA (20 mg/kg/day) improves insulin resistance in patients with NAFLD (iii) UDCA improves hepatobiliary transporter expression in NAFLD	Baseline and 3 weeks
Secondary	Changes in serum bile acids and lipids	relative changes in hepatic basolateral transport proteins MRP3, MRP4, OATP, SLC21A1; relative changes in m RNA expression levels of BAAT; CYP3A4, CYP7A1, CYP27, CYP8B1, UGT1A1, UGT2B4, UGT2B7, SULT2A1, HNF-4a, PXR/NR1I2, RXR/NR1B1; PERK, XBP-1, SREBP-1c; TNF-a, IL-6, IL-10, MCP-1, CxCl-1; relative change in serum bile acids; relative change in plasma 7a-hydroxy-4-cholesten-3-one and FGF-19; relative changes in total cholesterol, LDL-C, HDL-C, Apo A1, Apo B, in Lp(A)	Baseline and 3 weeks