Obese, Overweight, Type 2 Diabetes Mellitus
Conditions
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.
Interventions
RADIATIONGastric Emptying test
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.
OTHERMixed Oral Glucose Tolerance test
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.
DRUGConjugated bile acids sodium
500 mg tablets taken orally twice daily for 28 (+/- 4) days
OTHERPlacebo
Placebo tablets taken orally twice daily for 28 (+/- 4) days
Sponsors
Satiogen Pharmaceuticals, Inc.
Mayo Clinic
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
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Postprandial Glucose | baseline to 1 month | Measurement of the glucose concentration in the bloodstream 6 hours after eating a meal |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ox Bile Extract 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
Gastric Emptying test: 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.
Mixed Oral Glucose Tolerance test: 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.
Conjugated bile acids sodium: 500 mg tablets taken orally twice daily for 28 (+/- 4) days
Placebo: Placebo tablets taken orally twice daily for 28 (+/- 4) days | 11 |
| Placebo 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
Gastric Emptying test: 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.
Mixed Oral Glucose Tolerance test: 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.
Conjugated bile acids sodium: 500 mg tablets taken orally twice daily for 28 (+/- 4) days
Placebo: Placebo tablets taken orally twice daily for 28 (+/- 4) days | 12 |
| Total | 23 |
Baseline characteristics
| Characteristic | Ox Bile Extract | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 60 years | 57 years | 53 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 | 11 Participants | 23 Participants | 12 Participants |
| Region of Enrollment United States | 11 participants | 23 participants | 12 participants |
| Sex: Female, Male Female | 7 Participants | 13 Participants | 6 Participants |
| Sex: Female, Male Male | 4 Participants | 10 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 12 |
| other Total, other adverse events | 0 / 11 | 0 / 12 |
| serious Total, serious adverse events | 0 / 11 | 0 / 12 |
Outcome results
Primary
Change in Postprandial Glucose
Measurement of the glucose concentration in the bloodstream 6 hours after eating a meal
Time frame: baseline to 1 month
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Ox Bile Extract | Change in Postprandial Glucose | -2803 mmol/6hr |
| Placebo | Change in Postprandial Glucose | 629 mmol/6hr |
p-value: <0.05ANCOVA