Influence of Gut Hormones on Food Intake After Roux-en-Y Gastric Bypass Surgery

Study Overview
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Brief Summary
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The aim of this study is to examine the effect of GLP-1 and other gut-secreted hormones (glucagon, GIP, grelin and PYY) on food-intake, appetite and glucose metabolism after Roux-en-Y gastric bypass surgery.

Detailed Description
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To do this the effect of combined GLP-1 receptor blockade by Exendin 9-39 and DPP-4-inhibition will be evaluated.

Official Title
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Influence of Gut Hormones on Food Intake After Roux-en-Y Gastric Bypass Surgery

Conditions
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Severe Obesity

Intervention / Treatment
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* Drug: exendin 9-39
* Drug: sitagliptin
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Uncomplicated RYGB performed 3-12 month proir to the study. Fasting plasma glucose <7.0 mM and HbA1c < 48 mmol/mol 3 month after RYGB. Exclusion Criteria: Fasting plasma glucose >7.0 mM and HbA1c > 48 mmol/mol 3 month after RYGB. Hemoglobin <6.5mM. Previous anaphylaxis when treated with Januvia or Byetta. Allergy for sitagliptin. Dysregulated hypothyroidism. Use of antithyroid treatment. Late diabetic complications as retinopathy, renal insuffiency, neuropathy or previous pancreatitis. Bad compliance. Complications to RYGB: Documented reactive hypoglycaemia, severe dumping (with vomiting, diarrhea or severe abdominal pain after food intake).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Saline<br>Mixed meal test and ad libitum meal test duing infusion of saline | Other: Placebo<br>* Saline<br>|
| Experimental: Exendin 9-39<br>Mixed meal test and ad libitum meal test duing infusion of exendin 9-39, 900 pmol/kg/min | Drug: exendin 9-39<br>* Exendin 9-39 is a specific GLP-1 receptor antagonist<br>* Other names: GLP-1 antagonist;|
| Experimental: DPP-4 Inhibition<br>Mixed meal test and ad libitum meal test during intake of sitagliptin 100 mg * 2 | Drug: sitagliptin<br>* DPP-4 Inhibition<br>* Other names: Januvia;|
| Experimental: Exendin 9-39 / DPP 4-Inhibition<br>Mixed meal test and ad libitum meal test duing infusion of exendin 9-39, 900 pmol/kg/min and intake of sitagliptin 100 mg * 2 | Drug: exendin 9-39<br>* Exendin 9-39 is a specific GLP-1 receptor antagonist<br>* Other names: GLP-1 antagonist;Drug: sitagliptin<br>* DPP-4 Inhibition<br>* Other names: Januvia;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ad libitum food intake (changes in food intake) | Evaluated by changes in food intake between the placebo day and the day with both administration of exendin 9-39 and DPP 4 Inhibitor | 3-12 month after RYGB | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose metabolism (iAUC of glucose and c-pep after a meal) | Evaluated by iAUC of glucose and c-pep after a meal | 3-12 month after RYGB | 
| Gut-derived hormone profiles (iAUC of GLP-1, PYY, GIP and glucagon after a meal) | Evaluated by iAUC of GLP-1, PYY, GIP and glucagon after a meal | 3-12 month after RYGB | 
| Appetite measurement (VAS-scores) | Evaluated by VAS-scores | 3-12 month after RYGB |