Ursodiol on Insulin Sensitivity, Gastric Emptying and Body Weight With Type 2 Diabetes on Metformin

April 18, 2019 updated by: Michael Camilleri, MD, Mayo Clinic

Effect of Delayed-Release Ursodeoxycholic Acid on Insulin Sensitivity, Gastric Emptying and Body Weight in Overweight or Obese Patients With Type 2 Diabetes on Metformin Treatment

This study will evaluate whether bile acids are able to increase insulin sensitivity and enhance glycemic control in T2DM patients, as well as exploring the mechanisms that enhance glycemic control. These observations will provide the preliminary data for proposing future therapeutic as well as further mechanistic studies of the role of bile acids in the control of glycemia in T2DM.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Background: Intra-jejunal administration of bile acids improves insulin sensitivity.

Hypothesis: The bile acid, ursodeoxycholic acid (UDCA) in delayed (ileocolonic)-release formulation, stimulates bile acid membrane receptor (TGR-5) and farnesol X (FXR) receptors in the ileum and colon, increasing the secretion of Fibroblast growth factor 19 (FGF-19), GLP-1, oxyntomodulin (OXM), and Peptide (PYY3-36), improving insulin sensitivity and inducing weight loss.

Aim: To study the effect of an ileocolonic formulation of UDCA on insulin sensitivity, postprandial plasma glycemia and incretin levels, gastric emptying and body weight in overweight or obese type 2 diabetic subjects on monotherapy with metformin.

Study design: This is a single center, placebo-controlled, parallel group, single dose randomized controlled trial to study the effect of delayed (ileocolonic)-release UDCA 600 mg twice daily on insulin sensitivity, gastric emptying of liquids and solids (measured by scintigraphy)and weight loss in overweight or obese type 2 diabetic subjects. Participants will be receiving monotherapy with metformin. Blood samples will be collected at defined times to measure glycemia and the incretin (GLP-1, OXM, PYY3-36) fasting levels and responses to the meal.

Anticipated Results: In comparison with placebo, UDCA will increase insulin sensitivity, enhance glycemic control, increase postprandial incretins, and delay gastric emptying (GE) of liquids.

Significance: This study will prove that ileocolonic-release UDCA enhances glycemic control in T2DM patients.

Study Type

Interventional

Enrollment (Actual)

24

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic in Rochester

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 68 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Overweight or Obese subjects with BMI> 25 Kg/m2 with Type 2 Diabetes mellitus on Metformin, receiving standard of care for Type 2 DM. Otherwise individuals who are not currently on treatment for cardiac, pulmonary, gastrointestinal, hepatic, renal, hematological, neurological, endocrine (other than T2DM) and unstable psychiatric disease.

Men or women. Women of childbearing potential will have a negative pregnancy test before initiation of medication.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ursodiol
Ursodeoxycholic acid (UDCA) 600mg in delayed (ileocolonic)-release to be taken twice daily
Drug: Ursodiol
Other Names:
  • Ursodeoxycholic acid
Placebo Comparator: Placebo
matching placebo capsules to be taken twice daily
Drug: Ursodiol
Other Names:
  • Ursodeoxycholic acid

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Area Above Basal (AAB) for Glucose
Time Frame: baseline, post-treatment approximately 14 - 17 days
Mixed meal glucose results are used to calculate the area above basal (AAB) for glucose. The glycemic index of a food is defined as the incremental area under the two-hour blood glucose response curve (AUC) following an overnight fast and ingestion of a food with a certain quantity of available carbohydrate (usually 50 g).
baseline, post-treatment approximately 14 - 17 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Fasting Glucose
Time Frame: baseline, post-treatment approximately 14 - 17 days
Serum glucose measurements taken after 10 hours of fasting.
baseline, post-treatment approximately 14 - 17 days
Change in Insulin Sensitivity
Time Frame: baseline, post-treatment approximately 14 - 17 days
Insulin sensitivity will be calculated by the oral minimal model.
baseline, post-treatment approximately 14 - 17 days
Gastric Emptying of Liquids (T1/2)
Time Frame: post-treatment, approximately 14-17 days
The time for half of the ingested liquids to leave the stomach. Following a meal with milk labeled with indium In111 diethylenetriaminepentaacetate (0.1 mCi), gastric emptying of liquids was assessed with scintigraphy imaging.
post-treatment, approximately 14-17 days
Gastric Emptying of Solids (T1/2)
Time Frame: post-treatment, approximately 14-17 days
The time for half of the ingested solids to leave the stomach. Following a meal consisting of two eggs labeled with technetium Tc 99m sulfur colloid (1 mCi) served with 50g of Canadian bacon and one slice of bread gastric emptying of solids was assessed with scintigraphy imaging.
post-treatment, approximately 14-17 days
Change in Weight
Time Frame: baseline, post-treatment approximately 14 - 17 days
Change in subject's weight, in kilograms
baseline, post-treatment approximately 14 - 17 days
Change in Body Mass Index
Time Frame: baseline, post-treatment approximately 14 - 17 days
Change in subjects BMI, in kilograms per meter squared.
baseline, post-treatment approximately 14 - 17 days
Change in FGF-19
Time Frame: baseline, post-treatment approximately 14 - 17 days
Change in fasting fibroblast growth factor (FGF)-19 expression.
baseline, post-treatment approximately 14 - 17 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mayo Clinic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2013

Primary Completion (Actual)

January 1, 2017

Study Completion (Actual)

March 1, 2017

Study Registration Dates

First Submitted

January 9, 2014

First Submitted That Met QC Criteria

January 9, 2014

First Posted (Estimate)

January 13, 2014

Study Record Updates

Last Update Posted (Actual)

May 8, 2019

Last Update Submitted That Met QC Criteria

April 18, 2019

Last Verified

April 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 13-004908

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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