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

NCT03201952 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: 162023
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

Glucose Intolerance; Gastric Bypass Surgery

Keywords

Glucose; Ileostomy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Change in insulin Level

  Baseline to 3 hours

• Change in GLP-1 Level

  Baseline to 3 hours

Study Arms (2)

Ursodeoxycholic Acid/Placebos

ACTIVE COMPARATOR

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; Drug: Placebos

Placebos/Ursodeoxycholic Acid

ACTIVE COMPARATOR

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; Drug: Placebos

Interventions

Ursodeoxycholic Acid DRUG

Ileostomy administration of 300mg UDCA once

Also known as: UDCA

Placebos/Ursodeoxycholic Acid; Ursodeoxycholic Acid/Placebos

Placebos DRUG

Ileostomy administration of 5cc saline placebo once

Also known as: Saline

Placebos/Ursodeoxycholic Acid; Ursodeoxycholic Acid/Placebos

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Related 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.

  PMID: 26196952 BACKGROUND

• 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.

  PMID: 26197299 BACKGROUND

MeSH Terms

Conditions

Glucose Intolerance

Interventions

Ursodeoxycholic Acid; Sodium Chloride

Condition Hierarchy (Ancestors)

Hyperglycemia; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Deoxycholic Acid; Cholic Acids; Bile Acids and Salts; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Cholanes; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Naji Abumrad, MD

  Vanderbilt University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Fellow

Model Details: 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.

Study Record Dates

• First Submitted: June 22, 2017
• First Posted: June 28, 2017
• Study Start: February 1, 2018
• Primary Completion: May 1, 2020
• Study Completion: May 1, 2020
• Last Updated: April 20, 2021

Record last verified: 2021-04

Locations

US (1)