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Examination of the Metabolic Effects of Direct Bile Salt Delivery to the Ileum in Humans

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ClinicalTrials.gov Identifier: NCT03201952
Recruitment Status : Recruiting
First Posted : June 28, 2017
Last Update Posted : February 7, 2020
Sponsor:
Information provided by (Responsible Party):
Michael Dole, Vanderbilt University Medical Center

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.

Condition or disease Intervention/treatment Phase
Glucose Intolerance Gastric Bypass Surgery Drug: Ursodeoxycholic Acid Drug: Placebos Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
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.
Masking: Single (Participant)
Primary Purpose: Basic Science
Official Title: Examination of the Metabolic Effects of Direct Bile Salt Delivery to the Ileum in Humans
Actual Study Start Date : February 1, 2018
Estimated Primary Completion Date : July 1, 2021
Estimated Study Completion Date : July 1, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sodium

Arm Intervention/treatment
Active Comparator: 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.
Drug: Ursodeoxycholic Acid
Ileostomy administration of 300mg UDCA once
Other Name: UDCA

Drug: Placebos
Ileostomy administration of 5cc saline placebo once
Other Name: Saline

Active Comparator: 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.
Drug: Ursodeoxycholic Acid
Ileostomy administration of 300mg UDCA once
Other Name: UDCA

Drug: Placebos
Ileostomy administration of 5cc saline placebo once
Other Name: Saline




Primary Outcome Measures :
  1. Change in glucose level [ Time Frame: 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 Outcome Measures :
  1. Change in insulin Level [ Time Frame: 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

  2. Change in GLP-1 Level [ Time Frame: 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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03201952


Contacts
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Contact: Michael R Dole, MD 8646161389 michael.dole@vanderbilt.edu
Contact: Charles R Flynn, PhD robb.flynn@vanderbilt.edu

Locations
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United States, Tennessee
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Michael Dole, MD    864-616-1389    michael.dole@vanderbilt.edu   
Sponsors and Collaborators
Vanderbilt University Medical Center
Investigators
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Study Director: Naji Abumrad, MD Vanderbilt University
Publications:
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Responsible Party: Michael Dole, Clinical Fellow, Vanderbilt University Medical Center
ClinicalTrials.gov Identifier: NCT03201952    
Other Study ID Numbers: 162023
First Posted: June 28, 2017    Key Record Dates
Last Update Posted: February 7, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Michael Dole, Vanderbilt University Medical Center:
Glucose
Ileostomy
Additional relevant MeSH terms:
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Glucose Intolerance
Hyperglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Ursodeoxycholic Acid
Cholagogues and Choleretics
Gastrointestinal Agents