Clinical trial NCT06121245: The PRO-SOma COla (PROSOCO) Study
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Healthy
Keywords: somatostatin
secretion
peptide
pro-somatostatin 1-64
Lead sponsor: University of Copenhagen
Sponsor class: OTHER
Collaborators: name: Hvidovre University Hospital
First posted: 2023-11-07
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Randomized, double-blind, placebo-controlled, crossover study
Primary purpose: BASIC_SCIENCE

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Plasma concentration of pro-somatostatin 1-64
timeFrame: baseline samples, 7, 10, 15, 20, 25, 30, 45, 60, 90, 120 min
Secondary outcomes:
measure: Plasma concentration of gastrin
timeFrame: baseline samples, 7, 10, 15, 20, 25, 30, 45, 60, 90, 120 min
measure: Plasma concentration of cholecystokinin
timeFrame: baseline samples, 7, 10, 15, 20, 25, 30, 45, 60, 90, 120 min
measure: Plasma concentration of secretin
timeFrame: baseline samples, 7, 10, 15, 20, 25, 30, 45, 60, 90, 120 min
measure: Plasma concentration of pancreatic polypeptide
timeFrame: baseline samples, 7, 10, 15, 20, 25, 30, 45, 60, 90, 120 min
measure: Plasma concentration of glucose
timeFrame: baseline samples, 7, 10, 15, 20, 25, 30, 45, 60, 90, 120 min
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: University of Copenhagen
state: Capital
city: Hvidovre
country: Denmark
facility: Hvidovre University Hospital
state: Capital
Study officials:
affiliation: University of Copenhagen
name: Jens J Holst, MD
role: PRINCIPAL_INVESTIGATOR
References: