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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02033876
Recruitment Status : Completed
First Posted : January 13, 2014
Last Update Posted : November 13, 2017
Information provided by (Responsible Party):
Michael Camilleri, Mayo Clinic

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus Drug: Ursodiol Phase 2

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 TGR-5 and FXR receptors in the ileum and colon, increasing the secretion of FGF-19, GLP-1, oxyntomodulin (OXM), and 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 GE of liquids.

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

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : October 2013
Actual Primary Completion Date : January 2017
Actual Study Completion Date : March 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Body Weight
Drug Information available for: Ursodiol

Arm Intervention/treatment
Experimental: Ursodiol
Ursodeoxycholic acid (UDCA) 600mg in delayed (ileocolonic)-release to be taken twice daily
Drug: Ursodiol
Other Name: Ursodeoxycholic acid

Placebo Comparator: Placebo
matching placebo capsules to be taken twice daily
Drug: Ursodiol
Other Name: Ursodeoxycholic acid

Primary Outcome Measures :
  1. Reduction in area above basal (AAB) for Glucose [ Time Frame: 14-17days ]

Secondary Outcome Measures :
  1. Fasting glucose [ Time Frame: 14-17 days ]
  2. Insulin sensitivity calculated by the oral minimal model [ Time Frame: 14 - 17 days ]
  3. Gastric emptying of liquids (T1/2) [ Time Frame: 14 - 17 days ]
  4. Gastric emptying of solids (T1/2) [ Time Frame: 14 - 17 days ]
  5. Weight change, kg [ Time Frame: 14 - 17 days ]
  6. Insulin secretion calculated by the oral minimal model [ Time Frame: 14 - 17 days ]
  7. 24 hour colonic geometric center [ Time Frame: 14 - 17 days ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

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 identifier (NCT number): NCT02033876

United States, Minnesota
Mayo Clinic in Rochester
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Principal Investigator: Michael Camilleri, MD Mayo Clinic

Responsible Party: Michael Camilleri, Professor of Medicine, Pharmacology and Physiology, Mayo Clinic Identifier: NCT02033876     History of Changes
Other Study ID Numbers: 13-004908
First Posted: January 13, 2014    Key Record Dates
Last Update Posted: November 13, 2017
Last Verified: November 2017

Additional relevant MeSH terms:
Ursodeoxycholic Acid
Diabetes Mellitus
Diabetes Mellitus, Type 2
Insulin Resistance
Body Weight
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Signs and Symptoms
Hypoglycemic Agents
Physiological Effects of Drugs
Cholagogues and Choleretics
Gastrointestinal Agents