Effect of Endoplasmic Reticulum Stress on Metabolic Function (TUDCA/PBA)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00771901
First received: October 10, 2008
Last updated: December 9, 2013
Last verified: December 2013

October 10, 2008
December 9, 2013
February 2008
December 2013   (final data collection date for primary outcome measure)
Determine the effect of treatment with TUDCA or PBA on body fat distribution. [ Time Frame: four weeks ] [ Designated as safety issue: No ]
Determine the effect of treatment with TUDCA on body fat distribution. [ Time Frame: four weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00771901 on ClinicalTrials.gov Archive Site
  • Determine the effect of TUDCA or PBA on in vivo insulin sensitivity [ Time Frame: four weeks ] [ Designated as safety issue: No ]
  • Determine the effect of TUDCA or PBA on hepatic VLDL-triglyceride (TG) and VLDL-apolipoprotein-B100 (apoB-100) secretion rates [ Time Frame: four weeks ] [ Designated as safety issue: No ]
  • Determine the effect of TUDCA or PBA on skeletal muscle intracellular insulin signaling, fatty acid oxidation, and markers of inflammation, assessed by evaluating skeletal muscle biopsies ex vivo. [ Time Frame: four weeks ] [ Designated as safety issue: No ]
  • Determine the effect of TUDCA or PBA on Adipose tissue insulin signaling, ER stress, and inflammation, assessed by evaluating adipose tissue biopsies ex vivo. [ Time Frame: four weeks ] [ Designated as safety issue: No ]
  • Determine the effect of TUDCA on in vivo insulin sensitivity [ Time Frame: four weeks ] [ Designated as safety issue: No ]
  • Determine the effect of TUDCA on hepatic VLDL-triglyceride (TG) and VLDL-apolipoprotein-B100 (apoB-100) secretion rates [ Time Frame: four weeks ] [ Designated as safety issue: No ]
  • Determine the effect of TUDCA on skeletal muscle intracellular insulin signaling, fatty acid oxidation, and markers of inflammation, assessed by evaluating skeletal muscle biopsies ex vivo. [ Time Frame: four weeks ] [ Designated as safety issue: No ]
  • Determine the effect of TUDCA on Adipose tissue insulin signaling, ER stress, and inflammation, assessed by evaluating adipose tissue biopsies ex vivo. [ Time Frame: four weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Effect of Endoplasmic Reticulum Stress on Metabolic Function
Effect of Endoplasmic Reticulum Stress on Metabolic Function

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.

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:

  1. 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.
  2. 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.
  3. Hepatic VLDL-triglyceride (TG) and VLDL-apolipoprotein-B100 (apoB-100) secretion rates, assessed by stable isotopically labeled tracer infusion methods.
  4. Skeletal muscle intracellular insulin signaling, fatty acid oxidation, and markers of inflammation, assessed by evaluating skeletal muscle biopsies ex vivo.
  5. Adipose tissue insulin signaling, ER stress, and inflammation, assessed by evaluating adipose tissue biopsies ex vivo.
Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Basic Science
  • Insulin Resistance
  • Diabetes
  • Obesity
  • 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
  • Other: placebo
    7 pills daily for 4 weeks
  • Drug: sodium phenylbutyrate
    20g/day for four weeks.
    Other Name: PBA
  • Placebo Comparator: Placebo
    Subjects will be given a placebo rather than tauroursodeoxycholic acid.
    Intervention: Other: placebo
  • Experimental: tauroursodeoxycholic acid
    Subjects will receive tauroursodeoxycholic acid for four weeks.
    Intervention: Drug: tauroursodeoxycholic acid
  • Experimental: PBA
    Subjects will receive sodium phenylbutyrate for four weeks.
    Intervention: Drug: sodium phenylbutyrate
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
30
December 2014
December 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • BMI range 30 to 45
  • sedentary (defined as regular exercise < 1 h per week or < 2 x/week for the last 6 months)

Exclusion Criteria:

  • active or previous infection with hepatitis B or C
  • liver diseases
  • history of alcohol abuse
  • current alcohol consumption > 20 g/day
  • severe hypertriglyceridemia ( > 400 mg/dL)
  • active peptic ulcer disease
  • taking cholestyramine or oral contraceptives
  • women who are pregnant or lactating
Both
18 Years to 65 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00771901
07-1114
No
Washington University School of Medicine
Washington University School of Medicine
Not Provided
Principal Investigator: Samuel Klein, MD Washington University School of Medicine
Washington University School of Medicine
December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP