Ursodeoxycholic Acid in Bariatric Surgery

NCT01548079 | Completed

• 1 other identifier: UDCAINBS
• Study Type: interventional
• Target: 40
• Locations: 0 countries
• Sites: N/A

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 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.

Conditions

Non-alcoholic Fatty Liver Disease; Morbid Obesity

Keywords

ursodeoxycholic acid; fatty liver disease; morbid obesity; bariatric surgery; NAFLD

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Changes in serum bile acids and lipids

  Baseline and 3 weeks

Study Arms (2)

Control

NO INTERVENTION

Untreated controls

Ursodeoxycholic acid

ACTIVE COMPARATOR

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

Drug: Ursodeoxycholic Acid (UDCA)

Interventions

Ursodeoxycholic Acid (UDCA) DRUG

20mg/kg/day UDCA in three weeks

Ursodeoxycholic acid

Eligibility Criteria

• Age: 25 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• BMI ≥ 35 kg/m2
• Patients eligible to bariatric surgery
• Patients should have given their written consent to participate in this study

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sahlgrenska University Hospital: lead

Related Publications (1)

• Mueller M, Castro RE, Thorell A, Marschall HU, Auer N, Herac M, Rodrigues CMP, Trauner M. Ursodeoxycholic acid: Effects on hepatic unfolded protein response, apoptosis and oxidative stress in morbidly obese patients. Liver Int. 2018 Mar;38(3):523-531. doi: 10.1111/liv.13562. Epub 2017 Sep 18.

  PMID: 28853202 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Obesity, Morbid

Interventions

Ursodeoxycholic Acid

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Obesity; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Deoxycholic Acid; Cholic Acids; Bile Acids and Salts; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Cholanes

Study Officials

• Hanns-Ulrich Marschall, MD, PhD

  Sahlgrenska Academy and University Hospital, Institute of Medicine, Dept. of Internal Medicine, University of Gothenburg, S-41345 Gothenburg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, senior consultant

Study Record Dates

• First Submitted: February 22, 2012
• First Posted: March 8, 2012
• Study Start: October 1, 2008
• Primary Completion: November 1, 2009
• Study Completion: May 1, 2010
• Last Updated: December 3, 2013

Record last verified: 2013-12