Ursodeoxycholic Acid in Bariatric Surgery - Full Text View

Purpose

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.

Condition	Intervention
Non-alcoholic Fatty Liver Disease Morbid Obesity	Drug: Ursodeoxycholic Acid (UDCA)


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacodynamics Study Intervention Model: Parallel Assignment Masking: 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.

Resource links provided by NLM:

MedlinePlus related topics: Liver Diseases Weight Loss Surgery

Drug Information available for: Ursodiol

Genetic and Rare Diseases Information Center resources: Visceral Steatosis

U.S. FDA Resources

Further study details as provided by Sahlgrenska University Hospital, Sweden:

Primary Outcome Measures:

Changes in regulators of lipid turnover [ Time Frame: Baseline and 3 weeks ] [ Designated as safety issue: No ]
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 [ Time Frame: Baseline and 3 weeks ] [ Designated as safety issue: No ]
- 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)


Enrollment:	40
Study Start Date:	October 2008
Study Completion Date:	May 2010
Primary Completion Date:	November 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

Eligibility


Ages Eligible for Study:	25 Years to 60 Years (Adult)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01548079

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

More Information


Responsible Party:	Hanns-Ulrich Marschall, Professor, senior consultant, Sahlgrenska University Hospital, Sweden
ClinicalTrials.gov Identifier:	NCT01548079 History of Changes
Other Study ID Numbers:	UDCAINBS
Study First Received:	February 22, 2012
Last Updated:	December 2, 2013
Health Authority:	Sweden: Medical Products Agency

Keywords provided by Sahlgrenska University Hospital, Sweden:


ursodeoxycholic acid fatty liver disease morbid obesity bariatric surgery NAFLD

Additional relevant MeSH terms:


Liver Diseases Non-alcoholic Fatty Liver Disease Digestive System Diseases Nutrition Disorders Ursodeoxycholic Acid Fatty Liver Obesity, Morbid	Obesity Overnutrition Overweight Body Weight Signs and Symptoms Cholagogues and Choleretics Gastrointestinal Agents

ClinicalTrials.gov processed this record on September 29, 2016