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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2011 by Washington University School of Medicine.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00771901
First received: October 10, 2008
Last updated: April 11, 2011
Last verified: April 2011
History of Changes
  Purpose

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 Intervention
Insulin Resistance
Diabetes
Obesity
 Drug: tauroursodeoxycholic acid
Other: placebo
Drug: sodium phenylbutyrate

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Basic Science
Official Title: Effect of Endoplasmic Reticulum Stress on Metabolic Function

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Determine the effect of treatment with TUDCA or PBA on body fat distribution. [ Time Frame: four weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 30
Study Start Date: February 2008
Estimated Study Completion Date: September 2011
Estimated Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: TUDCA
Experimental: PBA
Subjects will receive sodium phenylbutyrate for four weeks.
 Drug: sodium phenylbutyrate
20g/day for four weeks.
Other Name: PBA

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. 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.
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00771901

Contacts
Contact: Emily Jenkerson 1-866-362-5656

Locations
United States, Missouri
Washington University School of Medicine Recruiting
St. Louis, Missouri, United States, 63110
Contact: Emily Jenkerson     866-362-5656        
Principal Investigator: Samuel Klein, MD            
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Samuel Klein, MD Washington University School of Medicine
  More Information

No publications provided

Responsible Party: Samuel Klein, MD, Prinicipal Investigator, Washington University in St. Louis
ClinicalTrials.gov Identifier: NCT00771901     History of Changes
Other Study ID Numbers: 07-1114
Study First Received: October 10, 2008
Last Updated: April 11, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Washington University School of Medicine:
obesity
insulin resistance
type II diabetes

Additional relevant MeSH terms:
Diabetes Mellitus
Insulin Resistance
Obesity
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Hyperinsulinism
Overnutrition
Nutrition Disorders
Overweight
Body Weight
 Signs and Symptoms
4-phenylbutyric acid
Tauroursodeoxycholic acid
Taurochenodeoxycholic Acid
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Cholagogues and Choleretics
Gastrointestinal Agents
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on May 23, 2013