Effects of Bile Acids and Bile Acid Sequestrants 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 effects of bile acid and bile acids sequestrants on GLP-1 Secretion, during a meal, in patients after Roux-en-Y gastric bypass.

Official Title
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Effects of Chenodeoxycholic Acid and Colesevelam on GLP-1 Secretion, During a Meal, After Roux-en-Y Gastric Bypass

Conditions
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Severe Obesity

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


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 plasma 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: Placebo<br>Morning meal: brown bread, margarine, cheese, yoghurt, oatmeal, raisins, almonds, water, PCM. 25 ml water | Other: Water<br> <br> |
| Experimental: Chenodeoxycholic Acid<br>Morning meal: brown bread, margarine, cheese, yoghurt, oatmeal, raisins, almonds, water, PCM. Chenodeoxycholic acid (1250 mg) mixed in 25 ml yoghurt | Drug: Chenodeoxycholic Acid<br> <br> |
| Experimental: Colesevelam<br>Morning meal: brown bread, margarine, cheese, yoghurt, oatmeal, raisins, almonds, water, PCM. Colesevelam (3,75 g) dissolved in 25 ml water and mixed in 25 ml yoghurt. | Drug: Colesevelam<br> <br> |
| Experimental: Colesevelam x 2<br>plus (on another study day) 3,75 g colesevelam administered the evening before the experiment. Morning meal: brown bread, margarine, cheese, yoghurt, oatmeal, raisins, almonds, water, PCM. Colesevelam (3,75 g) dissolved in 25 ml water and mixed in 25 ml yoghurt. | 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, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes after mixed meal | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose levels |  | -10, 0, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes | 
| Insulin secretion |  | -10, 0, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes | 
| PYY secretion |  | -10, 0, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes | 
| Bile acids/FGF19 concentrations |  | -10, 0, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes | 
| Appetite measurements (VAS-score) |  | 0, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes | 
| PCM levels |  | Baseline, 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240 minutes | 
| C-peptide secretion |  | Baseline, 0, 5, 10, 20, 30, 45, 60, 90, 120, 180, 240 minutes | 
| Glucagon secretion |  | Baseline, 0, 10, 20, 30, 45, 60, 90, 120, 180, 240 minutes | 
| GIP secretion |  | 0, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes | 
| CCK secretion |  | 0, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes | 
| Ghrelin |  | 0, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes | 
| Total bile acid secretion |  | 0, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes |