Effect of Bile Acids and Bile Acid Sequstrants on GLP-1 Secretion After Roux-en-Y Gastric Bypass

Study Overview
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Brief Summary
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The purpose of this study is to examine the efffects of bile acid and bile acids sequestrants on GLP-1 secretion, in patients after Roux-en-Y gastric bypass.

Official Title
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Effect of Bile Acids and Bile Acid Sequstrants on GLP-1 Secretion After Roux-en-Y Gastric Bypass

Conditions
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Severe Obesity

Intervention / Treatment
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* Drug: Chenodeoxycholic Acid
* Drug: Colesevelam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Uncomplicated RYGB performed minimum 3 months prior to the study. Fasting glucose < 7,0 mM, HbA1c < 48 mmol/mol 3 months after RYGB Exclusion Criteria: Fasting plasma glucose > 7,0 mM, HbA1c > 48 mmol/mol 3 months after RYGB Dysregulated thyroid diseases, use of antithyroid treatment. Late diabetic complications as retinopathy, renal insufficiency, neuropathy or previous pancreatitis. Complications to RYGB. Documented reactive hypoglycaemia, severe dumping (vomiting, diarrhea, severe abdominal pain after food intake) Cholecystectomy.
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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chenodeoxycholic Acid<br>Chenodeoxycholic Acid (1250 mg) dissolved in 200 ml water. Here after 50 ml clean water. | Drug: Chenodeoxycholic Acid<br> <br> |
| Experimental: Chenodeoxycholic Acid and Colesevelam<br>Chenodeoxycholic Acid (1250 mg) and Colesevelam (3,75 g) dissolved in 200 ml water. Here after 50 ml clean water. | Drug: Chenodeoxycholic Acid<br> <br> Drug: Colesevelam<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GLP-1 secretion (evaluated by iAUC) |  | -10, 0, 5, 10, 15, 20, 25, 30, 45, 60, 90, 120, 180 and 240 minutes after medicin intake. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose levels |  | -10, -5, 0, 5, 10, 15, 20, 25, 30, 45, 60, 90, 120, 180 and 240 minutes | 
| PYY secretion |  | -10, 0, 5, 10, 15, 20, 25, 30, 45, 60, 90, 120, 180 and 240 minutes | 
| Glucagon secretion |  | -10, 0, 5, 10, 15, 20, 25, 30, 45, 60, 90, 120, 180 and 240 minutes | 
| GIP secretion |  | -10, 0, 5, 10, 15, 20, 25, 30, 45, 60, 90, 120, 180 and 240 minutes | 
| Insulin secretion |  | -10, -5, 0, 5, 10, 15, 20, 25, 30, 45, 60, 90, 120, 180 and 240 minutes | 
| C-peptide secretion |  | -10, -5, 0, 5, 10, 15, 20, 25, 30, 45, 60, 90, 120, 180 and 240 minutes | 
| CCK secretion |  | -10, 0, 5, 10, 15, 20, 25, 30, 45, 60, 90, 120, 180 and 240 minutes | 
| Total ghrelin |  | -10, 0, 5, 10, 15, 20, 25, 30, 45, 60, 90, 120, 180 and 240 minutes | 
| Total bile acid secretion |  | -10, 0, 5, 10, 15, 20, 25, 30, 45, 60, 90, 120, 180 and 240 minutes | 
| Bile acids fractions / FGF-19 concentrations |  | -10, 0, 5, 10, 15, 20, 25, 30, 45, 60, 90, 120, 180 and 240 minutes | 
| Appetite measurements (VAS-score) |  | -10, 30, 60, 120, 180 and 240 minutes |