Tauroursodeoxycholic Acid for Protease-inhibitor Associated Insulin Resistance
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Glucose Uptake
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
tauroursodeoxycholic acid
This group will receive 1.75 grams per day of tauroursodeoxycholic acid given once daily for 30 days.
干预措施: Tauroursodeoxycholic acid (Drug)
placebo
This 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.
干预措施: Placebo tablet (Other)
结局指标
主要结局
Glucose Uptake
时间窗: 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.
次要结局
- Body Composition(Pre-Treatment and Post 30 day-Treatment)
- Liver Fat(Pre-Treatment and Post 30 day-Treatment)
- Liver Function Tests(Pre-Treatment and Post 30 day-Treatment)