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

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02033876

Enrollment

Registered

2014-01-13

Start date

2013-10-31

Completion date

2017-03-31

Last updated

2019-05-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Type 2 Diabetes Mellitus

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.

Interventions

DRUGUrsodiol

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 70 Years

Healthy volunteers

Inclusion criteria

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.

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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.
Change in Fasting Glucose	baseline, post-treatment approximately 14 - 17 days	Serum glucose measurements taken after 10 hours of fasting.
Change in Body Mass Index	baseline, post-treatment approximately 14 - 17 days	Change in subjects BMI, in kilograms per meter squared.
Change in FGF-19	baseline, post-treatment approximately 14 - 17 days	Change in fasting fibroblast growth factor (FGF)-19 expression.
Change in Weight	baseline, post-treatment approximately 14 - 17 days	Change in subject's weight, in kilograms

Countries

United States

Participant flow

Participants by arm

Arm	Count
Ursodiol Ursodeoxycholic acid (UDCA) 600mg in delayed (ileocolonic)-release to be taken twice daily Ursodiol	12
Placebo matching placebo capsules to be taken twice daily Ursodiol	12
Total	24

Baseline characteristics

Characteristic	Ursodiol	Total	Placebo
Age, Continuous	62.5 years	58.9 years	57 years
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	12 Participants	24 Participants	12 Participants
Region of Enrollment United States	12 participants	24 participants	12 participants
Sex: Female, Male Female	6 Participants	12 Participants	6 Participants
Sex: Female, Male Male	6 Participants	12 Participants	6 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 12	0 / 12
other Total, other adverse events	0 / 12	0 / 12
serious Total, serious adverse events	0 / 12	0 / 12

Outcome results

Primary

Change in Area Above Basal (AAB) for Glucose

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).