Effect of Secretin in Functional Dyspepsia and Healthy Subjects

Effect of Secretin on Gastric Accommodation, Emptying and Post-nutrient Challenge Symptoms in Functional Dyspepsia and Healthy Subjects

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.

Study Overview

• Status: Completed
• Conditions: Healthy; Dyspepsia
• Intervention / Treatment: Drug: Human Secretin; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Patients with FD and prior documentation of normal or accelerated gastric emptying and/or reduced gastric accommodation.

Inclusion criteria:

• Able to provide written informed consent prior to any study procedures and be willing and able to comply with study procedures
• No medical problems or chronic diseases, other than functional dyspepsia, for that group
• Body mass index of 18-35 kg/m2
• Female subjects must have negative urine pregnancy tests and must not be lactating prior to receiving study medication and radiation exposure. For females able to bear children, a hormonal (i.e., oral, implantable, or injectable) and single-barrier method, or a double-barrier method of birth control must be used throughout the study. Female subjects unable to bear children must have this documented in the medical record [i.e., tubal ligation, hysterectomy, or post-menopausal (defined as a minimum of one year since the last menstrual period)].

Exclusion criteria:

• Unable or unwilling to provide informed consent or to comply with study procedures
• Diagnosis of other gastrointestinal diseases besides functional dyspepsia
• Structural or metabolic diseases that affect the GI system

• Unable to avoid the following over-the-counter medications 48 hours prior to the baseline period and throughout the study:

  • Medications that alter GI transit or motor function including laxatives, magnesium and aluminum containing antacids, prokinetics, erythromycin, buspirone, clonidine, tricyclic antidepressants, and secretin-norepinephrine reuptake inhibitors
  • Analgesic drugs including NSAIDs and COX-2 inhibitors
  • NOTE: Stable doses of thyroid replacement, estrogen replacement, low-dose aspirin for cardio-protection, low stable dose antidepressants of the SSRI class, and birth control (but with adequate backup contraception, as drug interactions with birth control have not been conducted) are permissible.
• History of recent surgery (within 60 days of screening)
• Acute or chronic illness or history of illness which in the opinion of the investigator could pose a threat or harm to the subject or obscure interpretation of laboratory test results or interpretation of study data, such as frequent angina, Class III or IV congestive heart failure, moderate impairment of renal or hepatic function, poorly controlled diabetes, etc.
• Any clinically significant abnormalities on physical examination or laboratory abnormalities identified in the medical record, as determined by the investigator
• Acute GI illness within 48 hours of initiation of the baseline period
• Females who are pregnant or breastfeeding
• History of excessive alcohol use or substance abuse
• Participation in an investigational study within the 30 days prior to dosing in the present study
• Any other reason, which in the opinion of the investigator, would confound proper interpretation of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy Controls: Secretin Then 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.	Drug: Human Secretin; Injected once over one minute; Other Names: ChiRhoStim; Drug: Placebo; Injected once over one minute; Other Names: Normal Saline
Experimental: Healthy Controls: Placebo Then 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.	Drug: Human Secretin; Injected once over one minute; Other Names: ChiRhoStim; Drug: Placebo; Injected once over one minute; Other Names: Normal Saline
Experimental: Functional Dyspepsia: Secretin Then 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.	Drug: Human Secretin; Injected once over one minute; Other Names: ChiRhoStim; Drug: Placebo; Injected once over one minute; Other Names: Normal Saline
Experimental: Functional Dyspepsia: Placebo Then 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.	Drug: Human Secretin; Injected once over one minute; Other Names: ChiRhoStim; Drug: Placebo; Injected once over one minute; Other Names: Normal Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Satiation	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.	60 minutes
Fasting Gastric Volume	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).	Baseline
Postprandial Volume	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).	15 minutes
Change in Gastric Accommodation	The change in gastric accommodation was measured in mL using the difference between the fasting gastric volume and the postprandial volume.	Baseline, 30 minutes
Gastric Emptying	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.	30 minutes
Change in Postprandial Symptoms	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'.	Baseline, 30 minutes

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Michael Camilleri, Mayo Clinic

Publications and helpful links

General Publications

• Brandler J, Miller LJ, Wang XJ, Burton D, Busciglio I, Arndt K, Harmsen WS, Camilleri M. Secretin effects on gastric functions, hormones and symptoms in functional dyspepsia and health: randomized crossover trial. Am J Physiol Gastrointest Liver Physiol. 2020 Apr 1;318(4):G635-G645. doi: 10.1152/ajpgi.00371.2019. Epub 2020 Feb 10.

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2018
• Primary Completion (Actual): July 1, 2019
• Study Completion (Actual): August 1, 2019

Study Registration Dates

• First Submitted: July 16, 2018
• First Submitted That Met QC Criteria: July 31, 2018
• First Posted (Actual): August 7, 2018

Study Record Updates

• Last Update Posted (Actual): June 11, 2020
• Last Update Submitted That Met QC Criteria: June 1, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Dyspepsia; Physiological Effects of Drugs; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Secretin
• Other Study ID Numbers: 18-003744; R01DK122280 (U.S. NIH Grant/Contract); R01DK115950 (U.S. NIH Grant/Contract); UL1TR002377 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No