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Ursodeoxycholic Acid in Bariatric Surgery

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ClinicalTrials.gov Identifier: NCT01548079
Recruitment Status : Completed
First Posted : March 8, 2012
Last Update Posted : December 3, 2013
Sponsor:
Information provided by (Responsible Party):
Hanns-Ulrich Marschall, Sahlgrenska University Hospital, Sweden

Study Description
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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.

Condition or disease Intervention/treatment Phase
Non-alcoholic Fatty Liver Disease Morbid Obesity Drug: Ursodeoxycholic Acid (UDCA) Not Applicable

Study Design
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Study Type : Interventional  (Clinical Trial)
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 : October 2008
Actual Primary Completion Date : November 2009
Actual Study Completion Date : May 2010

Resource links provided by the National Library of Medicine

Drug Information available for: Ursodiol

Arms and Interventions
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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
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Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. 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)


Eligibility Criteria
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Ages Eligible for Study:   25 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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
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Responsible Party: Hanns-Ulrich Marschall, Professor, senior consultant, Sahlgrenska University Hospital, Sweden
ClinicalTrials.gov Identifier: NCT01548079     History of Changes
Other Study ID Numbers: UDCAINBS
First Posted: March 8, 2012    Key Record Dates
Last Update Posted: December 3, 2013
Last Verified: December 2013

Keywords provided by Hanns-Ulrich Marschall, Sahlgrenska University Hospital, Sweden:
ursodeoxycholic acid
fatty liver disease
morbid obesity
bariatric surgery
NAFLD

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