Examination of the Metabolic Effects of Direct Bile Salt Delivery to the Ileum in Humans
| Status: | Recruiting |
|---|---|
| Conditions: | Endocrine |
| Therapuetic Areas: | Endocrinology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 8/12/2018 |
| Start Date: | February 1, 2018 |
| End Date: | July 1, 2019 |
| Contact: | Michael R Dole, MD |
| Email: | michael.dole@vanderbilt.edu |
| Phone: | 8646161389 |
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.
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.
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.
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.
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.
We found this trial at
1
site
1211 Medical Center Dr
Nashville, Tennessee 37232
Nashville, Tennessee 37232
(615) 322-5000
Phone: 864-616-1389
Vanderbilt Univ Med Ctr Vanderbilt University Medical Center (VUMC) is a comprehensive healthcare facility dedicated...
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