Ursodeoxycholic Acid in Bariatric Surgery

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.

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Key information

Conditions

Non-Alcoholic Fatty Liver Disease Body Weight Digestive System Diseases Fatty Liver Liver Diseases Morbid Obesity Nutrition Disorders Nutritional and Metabolic Diseases Obesity Obesity, Morbid Overnutrition Overweight Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

25 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Ursodeoxycholic acid (UDCA)

Drug

20mg/kg/day UDCA in three weeks

Primary outcomes

Changes in regulators of lipid turnover

Time frame: Baseline and 3 weeks

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

Secondary outcomes

Changes in serum bile acids and lipids

Time frame: Baseline and 3 weeks
- 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-4α, PXR/NR1I2, RXR/NR1B1; PERK, XBP-1, SREBP-1c; TNF-α, IL-6, IL-10, MCP-1, CxCl-1
- relative change in serum bile acids
- relative change in plasma 7α-hydroxy-4-cholesten-3-one and FGF-19
- relative changes in total cholesterol, LDL-C, HDL-C, Apo A1, Apo B, in Lp(A)

Sponsors and collaborators

Lead sponsor

Sahlgrenska University Hospital

Other

Registry information

Official study title

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

Important dates

Study start: 2008
Primary completion: 2009
Study completion: 2010
First posted: Mar 8, 2012
Registry last updated: Dec 3, 2013

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

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