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NCT Number: NCT01877551

Tauroursodeoxycholic Acid for Protease-inhibitor Associated Insulin Resistance

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.

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Key information

Conditions

HIV Related Insulin Resistance Endoplasmic Reticulum Stress Glucose Metabolism Disorders Hyperinsulinism Insulin Resistance Metabolic Diseases Nutritional and Metabolic Diseases Protease Inhibitor Related Insulin Resistance

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

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.

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • HIV+
  • receiving protease inhibitor containing antiretroviral therapy for >6 months
  • Undetectable viral load
  • insulin resistant
  • impaired fasting glucose (fasting blood glucose>100mg/dl)
  • impaired glucose tolerance (blood glucose >140mg/dl at 2 hours during oral glucose tolerance testing).
  • abstained from medications that affect glucose (e.g. prednisone, growth hormone)
  • stable medications for >3 months

Exclusion criteria

  • weight loss of >5% of body weight in prior 6 months
  • active gastrointestinal disease (gallstones, pancreatitis, hepatitis, diarrhea)
  • use of anti-diabetic medications
  • cardiovascular disease (uncontrolled hypertension, heart attack, heart failure, prior endocarditis)
  • history of or active substance abuse
  • blood clotting disorder or taking medications that affect blood clotting (e.g. coumadin, warfarin)
  • pregnant, planning to become pregnant or lactating
  • unable to give informed consent

Treatment and study plan

tauroursodeoxycholic acid

Drug

The intervention group will receive 1.75 grams of tauroursodeoxycholic acid daily for 30 days.

Other names: taurolite, tudcabil

Placebo tablet

Other

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.

Primary outcomes

  1. Glucose Uptake

    Time frame: Glucose uptake is measured at baseline and 30 days after study intervention

    We will examine the ability of insulin to cause muscle to take up insulin. Each subject will receive intravenous insulin for 6 hours to see how much sugar needs to be given intravenously to keep the blood sugar normal, a measure called glucose uptake. We will compare glucose uptake measured as the amount of 20% dextrose that is needed to keep the blood sugar at ~100mg/dl during insulin infusion before and after 30 days of treatment with drug or placebo.

Secondary outcomes

  1. Body Composition

    Time frame: Pre-Treatment and Post 30 day-Treatment

    We will measure how much fat is present in each subject before and after treatment with TUDCA or placebo.

  2. Liver Fat

    Time frame: Pre-Treatment and Post 30 day-Treatment

    We will use MRI to measure the relative (%) amount of fat in each subject's liver before and after 30 days of treatment. This will allow us to determine if the drug reduces liver fat. This is calculated by subtracting the amount of fat in the liver at the beginning of the study from the amount of fat in the liver after 30 days of treatment. Subjects who have claustrophobia or are unable to undergo MRI will not have this measure performed. Due to these reasons liver MRS was only performed in 10 patients in the tauroursodeoxycholic acid group and 9 subjects in the placebo group

  3. Liver Function Tests

    Time frame: Pre-Treatment and Post 30 day-Treatment

    We will measure liver function tests before and after the study drug to ensure that no abnormalities in liver function occurs with the drug.

Sponsors and collaborators

Lead sponsor

Washington University School of Medicine

Other

Collaborators

  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  • National Institutes of Health (NIH)

Registry information

Important dates

Study start
2013
Primary completion
2018
Study completion
2018
First posted
Jun 13, 2013
Registry last updated
Jan 27, 2020

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.

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