Examination of the Metabolic Effects of Direct Bile Salt Delivery to the Ileum in Humans
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 1
- 主要终点
- Change in glucose level
研究概览
简要总结
This project will evaluate distal intestinal bile salt administration in humans by deliving ursodeoxycholic acid (UDCA) into the terminal ileum of subjects with a pre-existing ileostomy and assessing several hormone levels following an oral glucose tolerance test compared to a placebo.
详细描述
Ursodeoxycholic acid (UDCA) is currently FDA-approved for the treatment of gallstone dissolution and primary biliary cirrhosis. Other than these two diseases, exploratory research - both preclinical and clinical - has demonstrated other beneficial effects of UDCA. For example, systemic administration of UDCA for several weeks (4-6 weeks) has been shown to improve insulin sensitivity in non-diabetic, obese individuals. Whether or not these effects on insulin sensitivity may be acute in nature and are detectable by OGTT are unknown. Based on growing knowledge of bile salt receptors in the gastrointestinal tract, at least some of these effects of bile salts on metabolism appear to be mediated by receptors constitutively expressed in the terminal ileum (e.g. TGR5 receptor that is upstream of GLP-1 and insulin secretion that control blood glucose levels). Thus, metabolic effects may be inducible with acute UDCA administration directly into this region of the intestine that could be useful in screening compounds or designing future mechanistic studies. This pilot study is designed to examine the effects of UDCA on oral glucose tolerance versus a placebo in non-diabetic across a range of body mass indexes by infusing UDCA directly into the ileum of volunteering subjects with a pre-existing ileostomy and measuring hormone response. The investigators aim to recruit approximately 4-5 volunteers in a lean BMI range (18.5-25 kg/m2), overweight (>25-29.9), class 1 obesity (>30-35 kg/m2), and class 2 obesity (>35-40 kg/m2) for a total of ~16-20 participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Able to give informed consent
- •Presence of an ileostomy > 2 months
- •Weight stable* for >2 months (i.e. no greater than 7% change in body weight the last 2 months)
排除标准
- •Crohn's Disease
- •Steroid use in the last 3 months
- •Documented/known diagnosis of type 1 diabetes or type 2 diabetes, chronic liver disease, chronic kidney disease, heart failure, cardiac dysrhythmias, or familial hypercholesterolemia
- •Current use of any over-the-counter or prescription oral bile salt
- •Currently pregnant
- •Current use of medications that are known to interact with Ursodiol
- •Current or former smoker within the last year.
研究组 & 干预措施
Ursodeoxycholic Acid/Placebos
During one of the subjects two randomized visits the subject will receive a 300mg elixir solution of ursodeoxycholic acid (UDCA) via their ileostomy that has been prepared by investigational drug services (IDS) in a 5cc elixir formulation during visit #1. During visit #2 subjects will receive a saline solution of totaling 5cc via their ileostomy that has been prepared by investigational drug services (IDS) in order to mimic the preparation of the medication comparator of ursodeoxycholic acid.
干预措施: Ursodeoxycholic Acid (Drug)
Ursodeoxycholic Acid/Placebos
During one of the subjects two randomized visits the subject will receive a 300mg elixir solution of ursodeoxycholic acid (UDCA) via their ileostomy that has been prepared by investigational drug services (IDS) in a 5cc elixir formulation during visit #1. During visit #2 subjects will receive a saline solution of totaling 5cc via their ileostomy that has been prepared by investigational drug services (IDS) in order to mimic the preparation of the medication comparator of ursodeoxycholic acid.
干预措施: Placebos (Drug)
Placebos/Ursodeoxycholic Acid
Subjects will receive a saline solution of totaling 5cc via their ileostomy that has been prepared by investigational drug services (IDS) in order to mimic the preparation of the medication comparator of ursodeoxycholic acid during visit #1. During visit #2 subject will receive a 300mg elixir solution of ursodeoxycholic acid (UDCA) via their ileostomy that has been prepared by investigational drug services (IDS) in a 5cc elixir formulation.
干预措施: Ursodeoxycholic Acid (Drug)
Placebos/Ursodeoxycholic Acid
Subjects will receive a saline solution of totaling 5cc via their ileostomy that has been prepared by investigational drug services (IDS) in order to mimic the preparation of the medication comparator of ursodeoxycholic acid during visit #1. During visit #2 subject will receive a 300mg elixir solution of ursodeoxycholic acid (UDCA) via their ileostomy that has been prepared by investigational drug services (IDS) in a 5cc elixir formulation.
干预措施: Placebos (Drug)
结局指标
主要结局
Change in glucose level
时间窗: 3 hours
Following UDCA administration and a 2 hour period to allow steady state, a 3 hour glucose tolerance test will be completed while measuring glucose change from baseline.
次要结局
- Change in insulin Level(Baseline to 3 hours)
- Change in GLP-1 Level(Baseline to 3 hours)
研究者
Michael Dole
Clinical Fellow
Vanderbilt University Medical Center