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

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ClinicalTrials.gov Identifier: NCT02033876
Recruitment Status : Completed
First Posted : January 13, 2014
Results First Posted : May 8, 2019
Last Update Posted : May 8, 2019
Sponsor:
Information provided by (Responsible Party):
Michael Camilleri, MD, 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 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.


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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: Allergy 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. 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).


Secondary Outcome Measures :
  1. Change in Fasting Glucose [ Time Frame: baseline, post-treatment approximately 14 - 17 days ]
    Serum glucose measurements taken after 10 hours of fasting.

  2. Change in Insulin Sensitivity [ Time Frame: baseline, post-treatment approximately 14 - 17 days ]
    Insulin sensitivity will be calculated by the oral minimal model.

  3. 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.

  4. 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.

  5. Change in Weight [ Time Frame: baseline, post-treatment approximately 14 - 17 days ]
    Change in subject's weight, in kilograms

  6. Change in Body Mass Index [ Time Frame: baseline, post-treatment approximately 14 - 17 days ]
    Change in subjects BMI, in kilograms per meter squared.

  7. Change in FGF-19 [ Time Frame: baseline, post-treatment approximately 14 - 17 days ]
    Change in fasting fibroblast growth factor (FGF)-19 expression.



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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
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.


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 ClinicalTrials.gov identifier (NCT number): NCT02033876


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

Additional Information:
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Responsible Party: Michael Camilleri, MD, Professor of Medicine, Pharmacology and Physiology, Mayo Clinic
ClinicalTrials.gov Identifier: NCT02033876     History of Changes
Other Study ID Numbers: 13-004908
First Posted: January 13, 2014    Key Record Dates
Results First Posted: May 8, 2019
Last Update Posted: May 8, 2019
Last Verified: April 2019
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Insulin Resistance
Body Weight
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Hyperinsulinism
Signs and Symptoms
Insulin
Metformin
Ursodeoxycholic Acid
Hypoglycemic Agents
Physiological Effects of Drugs
Cholagogues and Choleretics
Gastrointestinal Agents