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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT03201952
Other study ID # 162023
Secondary ID
Status Terminated
Phase Phase 1
First received
Last updated
Start date February 1, 2018
Est. completion date May 1, 2020

Study information

Verified date April 2021
Source Vanderbilt University Medical Center
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Terminated
Enrollment 2
Est. completion date May 1, 2020
Est. primary completion date May 1, 2020
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 18 Years and older
Eligibility 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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Ursodeoxycholic Acid
Ileostomy administration of 300mg UDCA once
Placebos
Ileostomy administration of 5cc saline placebo once

Locations

Country Name City State
United States Vanderbilt University Medical Center Nashville Tennessee

Sponsors (1)

Lead Sponsor Collaborator
Vanderbilt University Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (2)

Albaugh VL, Flynn CR, Cai S, Xiao Y, Tamboli RA, Abumrad NN. Early Increases in Bile Acids Post Roux-en-Y Gastric Bypass Are Driven by Insulin-Sensitizing, Secondary Bile Acids. J Clin Endocrinol Metab. 2015 Sep;100(9):E1225-33. doi: 10.1210/jc.2015-2467. Epub 2015 Jul 21. — View Citation

Flynn CR, Albaugh VL, Cai S, Cheung-Flynn J, Williams PE, Brucker RM, Bordenstein SR, Guo Y, Wasserman DH, Abumrad NN. Bile diversion to the distal small intestine has comparable metabolic benefits to bariatric surgery. Nat Commun. 2015 Jul 21;6:7715. doi: 10.1038/ncomms8715. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Change in glucose level 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. 3 hours
Secondary Change in insulin Level 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 Baseline to 3 hours
Secondary Change in GLP-1 Level 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 Baseline to 3 hours
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