Effect of Endoplasmic Reticulum Stress on Metabolic Function (TUDCA/PBA)
|ClinicalTrials.gov Identifier: NCT00771901|
Recruitment Status : Completed
First Posted : October 15, 2008
Results First Posted : May 28, 2018
Last Update Posted : May 28, 2018
Normally, the hormone insulin works to help keep blood sugar normal. However, as a person gains weight, insulin does not work as well and blood sugar tends to be a little higher than normal. This is called "insulin resistance".
Two investigational drugs (not approved by the Food and Drug Administration) for the treatment of high lipid levels or insulin resistance are being examined in this study: one drug is called tauroursodeoxycholic acid (TUDCA), the other is called sodium phenylbutyrate (PBA). This study is designed to test if TUDCA and/or PBA is effective in people who are obese with insulin resistance and high lipids. We hypothesize that pharmacologically-induced decreases in ER stress will improve insulin action and hepatic lipid metabolism in obese subjects.
|Condition or disease||Intervention/treatment||Phase|
|Insulin Resistance Diabetes Obesity||Drug: tauroursodeoxycholic acid Other: placebo Drug: sodium phenylbutyrate||Not Applicable|
A 4-week randomized, controlled trial will be conducted to evaluate the following specific aims in obese subjects:
Determine the effect of treatment with TUDCA or PBA on:
- Body fat distribution: a) intrahepatic triglyceride (IHTG) content, b) intramyocellular triglyceride (IMTG) content, and c) intra-abdominal fat content, assessed by using magnetic resonance spectroscopy and magnetic resonance imaging.
- In vivo insulin sensitivity in adipose tissue (suppression of lipolysis), liver (suppression of glucose production), and skeletal muscle (stimulation of glucose uptake), assessed by using the hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotope tracer infusion.
- VLDL-triglyceride (TG) and VLDL-apolipoprotein-B100 (apoB-100) secretion rates, assessed by stable isotopically labeled tracer infusion methods.
- Skeletal muscle intracellular insulin signaling, fatty acid oxidation, and markers of inflammation, assessed by evaluating skeletal muscle biopsies ex vivo.
- Adipose tissue insulin signaling, ER stress, and inflammation, assessed by evaluating adipose tissue biopsies ex vivo.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||101 participants|
|Intervention Model:||Parallel Assignment|
|Primary Purpose:||Basic Science|
|Official Title:||Effect of Endoplasmic Reticulum Stress on Metabolic Function|
|Actual Study Start Date :||February 2008|
|Actual Primary Completion Date :||December 2014|
|Actual Study Completion Date :||December 2014|
Placebo Comparator: Placebo
Subjects will be given a placebo rather than tauroursodeoxycholic acid.
7 pills daily for 4 weeks
Experimental: tauroursodeoxycholic acid
Subjects will receive tauroursodeoxycholic acid for four weeks.
Drug: tauroursodeoxycholic acid
1750 mg/day for four weeks. Seven pills daily, 2 with breakfast, 2 with lunch, and 3 with dinner.
Other Name: TUDCA
Subjects will receive sodium phenylbutyrate for four weeks.
Drug: sodium phenylbutyrate
20g/day for four weeks.
Other Name: PBA
- Body Composition [ Time Frame: Baseline and four weeks ]Fat mass (%)
- Insulin Sensitivity in the Liver [ Time Frame: Baseline and four weeks ]HISI (hepatic insulin sensitivity index). HISI is the inverse of the product of endogenous glucose production and plasma insulin concentration and provides an index of how well circulating insulin controls the amount of glucose supplied by the liver. A higher number is indicative of greater insulin sensitivity.
- VLDL-triglyceride (TG) Concentration [ Time Frame: Baseline and four weeks ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00771901
|United States, Missouri|
|Washington University School of Medicine|
|Saint Louis, Missouri, United States, 63110|
|Principal Investigator:||Samuel Klein, MD||Washington University School of Medicine|