Effect of Secretin in Functional Dyspepsia and Healthy Subjects

Phase 1

Completed

Conditions: Dyspepsia
Healthy

Interventions: Drug: Human Secretin
Drug: Placebo

Registration Number: NCT03617861

Lead Sponsor: Mayo Clinic

Brief Summary: Insights into the pathophysiology of functional dyspepsia, with recent demonstration of inflammation with eosinophilia and mastocytosis in the duodenum (3, 6, 7), providing a possible lead toward reduced secretion of a potential mediator of post-prandial gastric accommodation, the gastrointestinal peptide hormone secretin. The dominant site of synthesis and secretion of this hormone are enteroendocrine S cells in the duodenum. Inflammation-induced damage to these cells could produce a deficiency. Since intraluminal acid is a prominent stimulant of S cell secretion, the attempts to treat functional dyspepsia with anti-secretory medications could actually exacerbate a secretin deficiency syndrome. This raises the possibility of the therapeutic use of a secretin agonist or a positive allosteric modulator of the secretin receptor for patients with functional dyspepsia.

Detailed Description: The investigators will utilize single photon emission computed tomography (SPECT) methodology and gamma scintigraphy present in the GI laboratory of the outpatient Clinical Research Unit to study fasting gastric volumes and postprandial gastric accommodation responses and gastric emptying rates of a standardized meal in patients with functional dyspepsia and healthy subjects. Both groups will be studied twice, using crossover design, once with administration of secretin and once with placebo.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 20

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Functional Dyspepsia: Placebo Then Secretin	Placebo	Functional Dyspepsia subjects first receive placebo treatment (normal saline, matching Secretin dose) via IV over 1 min on Visit Day 1. After a 1 to 4 week washout period, they received the human Secretin 0.2 mcg/kg via IV over 1 min on Visit Day 2.
Healthy Controls: Placebo Then Secretin	Placebo	Healthy subjects first receive placebo treatment (normal saline, matching Secretin dose) via IV over 1 min on Visit Day 1. After a 1 to 4 week washout period, they received the human Secretin 0.2 mcg/kg via IV over 1 min on Visit Day 2.
Functional Dyspepsia: Secretin Then Placebo	Placebo	Functional Dyspepsia subjects first receive human Secretin 0.2 mcg/kg via IV over 1 min on Visit Day 1. After a 1 to 4 week washout period, they received the placebo treatment (normal saline, matching Secretin dose) via IV over 1 min on Visit Day 2.
Healthy Controls: Secretin Then Placebo	Placebo	Healthy subjects first receive human Secretin 0.2 mcg/kg via IV over 1 min on Visit Day 1. After a 1 to 4 week washout period, they received the placebo treatment (normal saline, matching Secretin dose) via IV over 1 min on Visit Day 2.
Healthy Controls: Secretin Then Placebo	Human Secretin	Healthy subjects first receive human Secretin 0.2 mcg/kg via IV over 1 min on Visit Day 1. After a 1 to 4 week washout period, they received the placebo treatment (normal saline, matching Secretin dose) via IV over 1 min on Visit Day 2.
Healthy Controls: Placebo Then Secretin	Human Secretin	Healthy subjects first receive placebo treatment (normal saline, matching Secretin dose) via IV over 1 min on Visit Day 1. After a 1 to 4 week washout period, they received the human Secretin 0.2 mcg/kg via IV over 1 min on Visit Day 2.
Functional Dyspepsia: Secretin Then Placebo	Human Secretin	Functional Dyspepsia subjects first receive human Secretin 0.2 mcg/kg via IV over 1 min on Visit Day 1. After a 1 to 4 week washout period, they received the placebo treatment (normal saline, matching Secretin dose) via IV over 1 min on Visit Day 2.
Functional Dyspepsia: Placebo Then Secretin	Human Secretin	Functional Dyspepsia subjects first receive placebo treatment (normal saline, matching Secretin dose) via IV over 1 min on Visit Day 1. After a 1 to 4 week washout period, they received the human Secretin 0.2 mcg/kg via IV over 1 min on Visit Day 2.

Primary Outcome Measures

Name	Time	Method
Maximum Satiation	60 minutes	Thirty (30) minutes after ingesting the meal of 300 mL radio-labeled Ensure drink, an additional Ensure drink was ingested at a constant rate of 30 mL/min until maximum tolerated volume was reached.
Fasting Gastric Volume	Baseline	Gastric fasting volume was measured prior to a meal of 300 mL standardized radio-labeled Ensure drink using an intravenous injection of Technetium Tc-99m pertechnetate and noninvasive single photon emission-computed tomography (SPECT).
Postprandial Volume	15 minutes	Postprandial volume was measured 15 minutes after ingestion of 300 mL standardized radio-labeled Ensure drink using an intravenous injection of Technetium Tc-99m pertechnetate and noninvasive single photon emission-computed tomography (SPECT).
Change in Gastric Accommodation	Baseline, 30 minutes	The change in gastric accommodation was measured in mL using the difference between the fasting gastric volume and the postprandial volume.
Gastric Emptying	30 minutes	Gastric emptying was measured via scintigraphy 30 minutes after ingestion of 300 mL of radio-labeled Ensure drink and was reported as the percentage of the radio-labeled liquid meal emptied from the stomach.
Change in Postprandial Symptoms	Baseline, 30 minutes	30 minutes after ingesting a meal of 300 mL of Ensure drink postprandial symptoms of fullness, nausea, bloating and pain were measured using a horizontal visual analog scales from 0 to 100, where 0 was 'none' and 100 was 'worst ever'.