View Clinical Trial (Medical Research Study)
Effect of Endoplasmic Reticulum Stress on Metabolic Function
| City: |
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St. Louis |
| State: |
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Missouri |
| Zip Code: |
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63110 |
| Conditions: |
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Insulin Resistance - Diabetes - Obesity |
| Purpose: |
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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.
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| Study Summary: |
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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.
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| Criteria: |
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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
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| NCT ID: |
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NCT00771901 |
| Primary Contact: |
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Principal Investigator
Samuel Klein, MD
Washington University School of Medicine
Emily Jenkerson
Phone: 1-866-362-5656
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| Backup Contact: |
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N/A |
| Location Contact: |
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St. Louis, Missouri 63110
United States
Emily Jenkerson
Phone: 866-362-5656
Site Status: Recruiting |
| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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June 19, 2013 |
| Modifications to this listing: |
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