Skip to main content
OpenTrials
Completed

NCT Number: NCT00771901

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Insulin Resistance Body Weight Diabetes Diabetes Mellitus Diabetes Mellitus, Type 2 Endocrine System Diseases Glucose Metabolism Disorders Hyperinsulinism Metabolic Diseases Nutrition Disorders Nutritional and Metabolic Diseases Obesity Overnutrition Overweight Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

tauroursodeoxycholic acid

Drug

1750 mg/day for four weeks. Seven pills daily, 2 with breakfast, 2 with lunch, and 3 with dinner.

Other names: TUDCA

Placebo

Other

7 pills daily for 4 weeks

Sodium Phenylbutyrate

Drug

20g/day for four weeks.

Other names: PBA

Primary outcomes

  1. Body Composition

    Time frame: Baseline and four weeks

    Fat mass (%)

Secondary outcomes

  1. 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.

  2. VLDL-triglyceride (TG) Concentration

    Time frame: Baseline and four weeks

Sponsors and collaborators

Lead sponsor

Washington University School of Medicine

Other

Registry information

Acronym: TUDCA/PBA

Important dates

Study start
2008
Primary completion
2014
Study completion
2014
First posted
Oct 15, 2008
Registry last updated
May 29, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.