NCT01877551

Tauroursodeoxycholic Acid for Protease-inhibitor Associated Insulin Resistance

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 27 (actual)
• Sponsor: Washington University School of Medicine · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

Rates of cardiovascular disease and diabetes are more than 2-fold greater in HIV infected people than the general population. Protease inhibitor booster antiretroviral therapy (PI-ART) which is used by \~50% of HIV infected people in the USA is an established risk factor for diabetes. Tauroursodeoxycholic acid (TUDCA), a naturally occurring bile salt, improves insulin sensitivity in HIV uninfected subjects, although the mechanisms for these benefits are unclear. This study will explore the hypothesis that TUDCA will improve insulin action in people with HIV who are receiving PI-ART. Further, this project will clarify the molecular mechanisms responsible for these improvements potentially benefiting society, irrespective of HIV status.

Detailed description

The purpose of this study is to determine if, and through which mechanisms, tauroursodeoxycholic acid improves insulin sensitivity in subjects with protease-inhibitor associated insulin resistance. The investigators will perform body composition analysis by using a DEXA machine, liver fat measurement by using an MRI, and hyperinsulinemic euglycemic clamp procedures in 48 HIV infected, insulin-resistant/prediabetic subjects before and after 30 days of treatment with tauroursodeoxycholic acid or matching placebo. Biopsies of adipose tissue and skeletal muscle will be taken during fasting conditions and during insulin infusion, before and after treatment to measure markers of endoplasmic reticulum stress and thyroid hormone deiodinase. Outcome measures: The primary outcome measures will be change in glucose clearance during insulin infusion, change in markers of endoplasmic reticulum stress and change in content of D2 in muscle.

Conditions

• HIV Related Insulin Resistance
• Protease Inhibitor Related Insulin Resistance
• Endoplasmic Reticulum Stress

Interventions

Type	Name	Description
DRUG	Tauroursodeoxycholic acid	The intervention group will receive 1.75 grams of tauroursodeoxycholic acid daily for 30 days.
OTHER	Placebo tablet	The placebo group will receive a placebo tablet that is identical to the treatment group except that it does not contain tauroursodeoxycholic acid. The pills will be taken once daily for 30 days.

Timeline

• Start date: 2013-09-01
• Primary completion: 2018-05-01
• Completion: 2018-05-01
• First posted: 2013-06-13
• Last updated: 2020-01-27
• Results posted: 2020-01-27

Locations

1 site across 1 country: United States