Ursodeoxycholic Acid in Bariatric Surgery

Sponsor

Sahlgrenska University Hospital, Sweden (Other)

Overall Status

Completed

CT.gov ID

NCT01548079

Collaborator

(none)

Enrollment

Arms

Duration (Months)

Study Details

Study Description

Brief 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

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.

Condition or Disease	Intervention/Treatment	Phase
Non-alcoholic Fatty Liver Disease Morbid Obesity	Drug: Ursodeoxycholic Acid (UDCA)	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

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

Study Start Date :

Oct 1, 2008

Actual Primary Completion Date :

Nov 1, 2009

Actual Study Completion Date :

May 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Control Untreated controls
Active Comparator: Ursodeoxycholic acid Oral ursodeoxycholic acid 20 mg/kg/day in three weeks	Drug: Ursodeoxycholic Acid (UDCA) 20mg/kg/day UDCA in three weeks

Arm

Intervention/Treatment

No Intervention: Control

Untreated controls

Active Comparator: Ursodeoxycholic acid

Oral ursodeoxycholic acid 20 mg/kg/day in three weeks

Drug: Ursodeoxycholic Acid (UDCA)

20mg/kg/day UDCA in three weeks

Outcome Measures

Primary Outcome Measures

Changes in regulators of lipid turnover [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 Outcome Measures

Changes in serum bile acids and lipids [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)

Eligibility Criteria

Criteria

Ages Eligible for Study:

25 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Sahlgrenska University Hospital, Sweden

Investigators

Principal Investigator: Hanns-Ulrich Marschall, MD, PhD, Sahlgrenska Academy and University Hospital, Institute of Medicine, Dept. of Internal Medicine, University of Gothenburg, S-41345 Gothenburg