Ursodeoxycholic Acid in Bariatric Surgery
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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. |
- 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
- 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 |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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 LocationsPlease refer to this study by its ClinicalTrials.gov identifier: NCT01548079
| 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
No publications provided
| 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:
|
Ursodeoxycholic Acid Cholagogues and Choleretics Gastrointestinal Agents Pharmacologic Actions Therapeutic Uses |
ClinicalTrials.gov processed this record on March 03, 2015