Ox Bile- Conjugated Bile Acids Sodium in Type II Diabetes Mellitus

Study Overview
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Brief Summary
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To study the effect of an ileocolonic formulation of ox bile extract on insulin sensitivity, postprandial glycemia and incretin levels, gastric emptying, body weight and fasting serum FGF-19 (fibroblast growth factor) levels in overweight or obese type 2 diabetic subjects on therapy with DPP4 (dipeptidyl peptidase-4) inhibitors (e.g. sitagliptin) alone or in combination with metformin.

Detailed Description
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This is a single-center, placebo-controlled, parallel-group, single dose, randomized, controlled trial. Participants will receive 28 days (+/- 4 days) of treatment to study the effect of delayed (ileocolonic)-release ox bile extract 500 mg BID (twice daily) on insulin sensitivity, gastric emptying of liquids and solids (measured by scintigraphy) and weight loss I overweight and obese type 2 diabetic subjects. Participants will be receiving therapy with DPP4 inhibitors alone or in combination with metformin. Blood samples will be collected at defined times to measure glycemia, FGF-19 and incretins (GLP-1 [glucagon-like peptide-1], OXM [oxyntomodulin], PYY 3-36 [peptide YY]) fasting levels and responses to the meal.

Official Title
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Effect of Delayed-Release Bile Acid on Insulin Sensitivity, Gastric Emptying and Body Weight in Overweight or Obese Patients With Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes Mellitus, Obese, Overweight

Intervention / Treatment
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* Radiation: Gastric Emptying test
* Other: Mixed Oral Glucose Tolerance test
* Drug: Conjugated bile acids sodium
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Overweight or obese subjects with BMI > 30 kg/m2 with type 2 diabetes mellitus taking DPP4 inhibitors alone or in combination with metformin. Women of childbearing potential will have a negative pregnancy test before initiation of medication and within 48 hours of receiving radioisotope. Exclusion criteria: Structural of metabolic diseases/conditions that affect the gastrointestinal system, or functional gastrointestinal disorders. Irritable bowel syndrome Bristol stool type classification 4-7 per Bowel Disease questionnaire. Subjects with other treatment for type 2 diabetes mellitus. Subjects with HbA1c > 8% Females who are pregnant or breastfeeding Concomitant use of appetite suppressants, orlistat, phentermine-topiramate ER or lorcaserin. Subjects who are not currently on treatment for cardiac, pulmonary, gastrointestinal, hepatic, renal, hematological, neurological, endocrine (other than type 2 diabetes mellitus), and unstable psychiatric disease. Subjects who have donated blood or plasma in the past 8 weeks. Subjects who have participated in another study within the past 30 days.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ox bile extract<br>Ox bile extract 500 mg tablets taken orally twice daily for 28 (+/- 4) days Gastric Emptying test, Waist and hip measurements, Mixed oral glucose tolerance test, Blood tests | Radiation: Gastric Emptying test<br>* participants eat a standardized meal labeled with radioactive markers (99mTc DTPA [diethylenetriaminepentaacetic acid] and In111 Chloride). They have scans taken at specific times after the meal to document the rate of gastric emptying.<br>Other: Mixed Oral Glucose Tolerance test<br>* Participants eat a meal containing 63g glucose in 240mL (milliliters) of skim milk, 2 scrambled eggs, 50g Canadian bacon and one slice of bread. Blood samples are taken prior to and for 6 hours after the meal at specific time points.<br>Drug: Conjugated bile acids sodium<br>* 500 mg tablets taken orally twice daily for 28 (+/- 4) days<br>* Other names: Ox Bile extract;|
| Placebo Comparator: Placebo<br>Matching placebo tablets taken orally twice daily for 28 (+/- 4) days Gastric Emptying test, Waist and hip measurements, Mixed oral glucose tolerance test, Blood tests | Radiation: Gastric Emptying test<br>* participants eat a standardized meal labeled with radioactive markers (99mTc DTPA [diethylenetriaminepentaacetic acid] and In111 Chloride). They have scans taken at specific times after the meal to document the rate of gastric emptying.<br>Other: Mixed Oral Glucose Tolerance test<br>* Participants eat a meal containing 63g glucose in 240mL (milliliters) of skim milk, 2 scrambled eggs, 50g Canadian bacon and one slice of bread. Blood samples are taken prior to and for 6 hours after the meal at specific time points.<br>Other: Placebo<br>* Placebo tablets taken orally twice daily for 28 (+/- 4) days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Postprandial Glucose | Measurement of the glucose concentration in the bloodstream 6 hours after eating a meal | baseline to 1 month |