Clinical trial NCT02871882: Ox Bile- Conjugated Bile Acids Sodium in Type II Diabetes Mellitus
Official title: Effect of Delayed-Release Bile Acid on Insulin Sensitivity, Gastric Emptying and Body Weight in Overweight or Obese Patients With Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 2 Diabetes Mellitus
Obese
Overweight
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: Satiogen Pharmaceuticals, Inc.
First posted: 2016-08-18
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion criteria:

1. Overweight or obese subjects with BMI \> 30 kg/m2 with type 2 diabetes mellitus taking DPP4 inhibitors alone or in combination with metformin.
2. Women of childbearing potential will have a negative pregnancy test before initiation of medication and within 48 hours of receiving radioisotope.

Exclusion criteria:

1. Structural of metabolic diseases/conditions that affect the gastrointestinal system, or functional gastrointestinal disorders.
2. Irritable bowel syndrome
3. Bristol stool type classification 4-7 per Bowel Disease questionnaire.
4. Subjects with other treatment for type 2 diabetes mellitus.
5. Subjects with HbA1c \> 8%
6. Females who are pregnant or breastfeeding
7. Concomitant use of appetite suppressants, orlistat, phentermine-topiramate ER or lorcaserin.
8. 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.
9. Subjects who have donated blood or plasma in the past 8 weeks.
10. Subjects who have participated in another study within the past 30 days.

Primary outcomes:
measure: Change in Postprandial Glucose
timeFrame: baseline to 1 month
Secondary outcomes:
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Andres Acosta, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Calderon G, McRae A, Rievaj J, Davis J, Zandvakili I, Linker-Nord S, Burton D, Roberts G, Reimann F, Gedulin B, Vella A, LaRusso NF, Camilleri M, Gribble FM, Acosta A. Ileo-colonic delivery of conjugated bile acids improves glucose homeostasis via colonic GLP-1-producing enteroendocrine cells in human obesity and diabetes. EBioMedicine. 2020 May;55:102759. doi: 10.1016/j.ebiom.2020.102759. Epub 2020 Apr 25.