Gastric Bypass Surgery, Glucose Intolerance
Conditions
Keywords
Glucose, Ileostomy
Brief summary
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.
Detailed description
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.
Interventions
DRUGUrsodeoxycholic Acid
Ileostomy administration of 300mg UDCA once
DRUGPlacebos
Ileostomy administration of 5cc saline placebo once
Sponsors
Vanderbilt University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Intervention model description
Each volunteering subject will participate in 2 study visits, receiving the placebo at one visit and investigation medication at the other visit. The order of these visits will be randomized.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* 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)
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in glucose level | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in insulin Level | Baseline to 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 insulin level |
| Change in GLP-1 Level | Baseline to 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 GLP-1 |
Countries
United States
Outcome results
None listed