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

Phase 2

Completed

Conditions: Type 2 Diabetes Mellitus

Interventions: Drug: Ursodiol

Registration Number: NCT02033876

Lead Sponsor: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 24

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ursodiol	Ursodiol	Ursodeoxycholic acid (UDCA) 600mg in delayed (ileocolonic)-release to be taken twice daily
Placebo	Ursodiol	matching placebo capsules to be taken twice daily

Primary Outcome Measures

Name	Time	Method
Change in Area Above Basal (AAB) for Glucose	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).

Secondary Outcome Measures

Name	Time	Method
Change in Weight	baseline, post-treatment approximately 14 - 17 days	Change in subject's weight, in kilograms
Change in Body Mass Index	baseline, post-treatment approximately 14 - 17 days	Change in subjects BMI, in kilograms per meter squared.
Change in Fasting Glucose	baseline, post-treatment approximately 14 - 17 days	Serum glucose measurements taken after 10 hours of fasting.
Change in FGF-19	baseline, post-treatment approximately 14 - 17 days	Change in fasting fibroblast growth factor (FGF)-19 expression.
Change in Insulin Sensitivity	baseline, post-treatment approximately 14 - 17 days	Insulin sensitivity will be calculated by the oral minimal model.
Gastric Emptying of Liquids (T1/2)	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.
Gastric Emptying of Solids (T1/2)	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.