The PRO-SOma COla (PROSOCO) Study

Study Overview
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Brief Summary
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The goal of this randomized, double-blind, placebo-controlled, crossover study is to determine whether it is possible to gauge the pattern of somatostatin secretion by measuring plasma concentrations of pro-somatostatin 1-64 (a stable peptide that is released in equimolar amounts alongside somatostatin) as a surrogate marker. During the study the release of somatostatin will be manipulated by changing the luminal pH of the stomach. Healthy participants will be studied in a randomized on two occasions. The day before both two study visits participants will ingest a capsule in the morning and a capsule in the evening. On one day the capsule will contain a proton pump inhibitor (Esomeprazol) to elevate the luminal pH of the stomach and on the other day the capsule will be a placebo. On the study days participants will ingest, in the mornng after an overnight fast, a coca cola zero + lemon juice to lower the luminal pH which willelicit the release of somatostatin. Blood samples will be collected before and after the ingestion of coca cola.

Detailed Description
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Somatostatin is a polypeptide that plays a key regulatory role in the gastrointestinal tract and pancreas. It has been attempted to determine in peripheral plasma samples the pattern of somatostatin release. However, due to the brief half-life of somatostatin this it turns out is difficult. Therefore, the investigators have developed an antibodies and a radioimmunoassay that measures concentrations of a stable peptide termed prosomatostatin 1-64. This peptide is released in equimolar amounts alongside somatostatin from the somatostatin-producing cells in the gut. The current study aims to demonstrate that prosomatostatin 1-64 can be picked up in peripheral plasma from human study participants. The release of somatostatin is increased when the pH of the stomach is low. The release of somatostatin will be elicited by asking participants coca cola zero with lemon juice. Participants will be studied on two occasions (on one day participants will be pretreated with a proton pump inhibitor, on the other day with a placebo). The two visits will be carried out as a placebo-controlled crossover study following a randomised schedule. If successful, pro-somatostatin 1-64 can be as a surrogate marker of somatostatin secretion. This will allow investigations of somatostatin secretion dynamics in humans.

Official Title
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Evaluating the Release of the Entero-pancreatic Hormone Somatostatin by Measuring Stable Co-secreted Prosomatostatin Moieties in the Plasma of Healthy Individuals - the PRO-SOma COla (PROSOCO) Study

Conditions
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Healthy

Intervention / Treatment
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* Other: Proton Pump inhibitor
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Non-diabetic fasting plasma glucose (< 7.0 mmol/L) at time of inclusion Normal weight and weight stable Written informed consent Exclusion Criteria: Pregnancy or breastfeeding Haemoglobin < 7.9 mmol/L Prior gastrointestinal operations excluding uncomplicated appendectomy Significant gastrointestinal symptoms (e.g. dyspepsia, postprandial pain) Intolerance to aspartame Use of medication that may influence blood pressure, gastrointestinal motor function, body weight or appetite (e.g. antihypertensive drugs, anticholinergic drugs (e.g. atropine, hyoscine), prokinetic drugs (metoclopramide, domperidone, erythromycin), orlistat, green tea extracts, astragalus, St. John's Wort etc.) Evidence of drug abuse, consumption of tobacco in any form or daily consumption of more than 20g alcohol History of gastrointestinal disease, including significant upper or lower gastrointestinal symptoms, pancreatitis, or previous gastrointestinal surgery including cholecystectomy (but not uncomplicated appendectomy) Participation in any other research studies within the previous 3 months Inability to give informed consent Non-Probability Sample: Any of a variety of other sampling processes, such as convenience sampling or invitation to volunteer

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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
Interventional Model Description: Randomized, double-blind, placebo-controlled, crossover study
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Esomeprazol<br>On the day before the study visits participants will ingest a capsule in the morning on a capsule in the evening containing Esomperazol | Other: Proton Pump inhibitor<br>* A proton pump inhibitor will be used as a tool to study the effect of pH changes in the stomach lumen on the release of somatostatin (evaluated by measurements of somatostatin and pro-somatostatin 1-64)<br>|
| Placebo Comparator: Placebo<br>On the day before the study visits participants will ingest a capsule in the morning on a capsule in the evening containing a placebo | Other: Placebo<br>* Placebo capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentration of pro-somatostatin 1-64 | Peptide released from D-cells in the gut in equimolar concentrations alongside somatostatin | baseline samples, 7, 10, 15, 20, 25, 30, 45, 60, 90, 120 min | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentration of gastrin | peptide hormone released from G cells in the antrum of the stomach | baseline samples, 7, 10, 15, 20, 25, 30, 45, 60, 90, 120 min | 
| Plasma concentration of cholecystokinin | peptide hormone released from I cells in the proximal small intestine | baseline samples, 7, 10, 15, 20, 25, 30, 45, 60, 90, 120 min | 
| Plasma concentration of secretin | Peptide hormone released from S cells in the small intestine | baseline samples, 7, 10, 15, 20, 25, 30, 45, 60, 90, 120 min | 
| Plasma concentration of pancreatic polypeptide | Peptide hormone released from the endocrine pancreas | baseline samples, 7, 10, 15, 20, 25, 30, 45, 60, 90, 120 min | 
| Plasma concentration of glucose |  | baseline samples, 7, 10, 15, 20, 25, 30, 45, 60, 90, 120 min | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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somatostatin, secretion, peptide, pro-somatostatin 1-64