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

April 25, 2018 updated by: Washington University School of Medicine

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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. 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.

Study Type

Interventional

Enrollment (Actual)

101

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Subjects will be given a placebo rather than tauroursodeoxycholic acid.
Other: placebo
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 Names:
  • TUDCA
Experimental: PBA
Subjects will receive sodium phenylbutyrate for four weeks.
Drug: sodium phenylbutyrate
20g/day for four weeks.
Other Names:
  • PBA

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Body Composition
Time Frame: Baseline and four weeks
Fat mass (%)
Baseline and four weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline and four weeks
VLDL-triglyceride (TG) Concentration
Time Frame: Baseline and four weeks
Baseline and four weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Washington University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2008

Primary Completion (Actual)

December 1, 2014

Study Completion (Actual)

December 1, 2014

Study Registration Dates

First Submitted

October 10, 2008

First Submitted That Met QC Criteria

October 14, 2008

First Posted (Estimate)

October 15, 2008

Study Record Updates

Last Update Posted (Actual)

May 29, 2018

Last Update Submitted That Met QC Criteria

April 25, 2018

Last Verified

April 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 07-1114

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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