Effect of Secretin in Functional Dyspepsia and Healthy Subjects

NCT03617861 | Completed Phase 1 Results FDA Drug

• 4 other identifiers: 18-003744R01DK115950R01DK122280UL1TR002377
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Dyspepsia; Healthy

Outcome Measures

Primary Outcomes (6)

• 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

Study Arms (4)

Healthy Controls: Secretin Then Placebo

EXPERIMENTAL

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; Drug: Placebo

Healthy Controls: Placebo Then Secretin

EXPERIMENTAL

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; Drug: Placebo

Functional Dyspepsia: Secretin Then Placebo

EXPERIMENTAL

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; Drug: Placebo

Functional Dyspepsia: Placebo Then Secretin

EXPERIMENTAL

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; Drug: Placebo

Interventions

Human Secretin DRUG

Injected once over one minute

Also known as: ChiRhoStim

Functional Dyspepsia: Placebo Then Secretin; Functional Dyspepsia: Secretin Then Placebo; Healthy Controls: Placebo Then Secretin; Healthy Controls: Secretin Then Placebo

Placebo DRUG

Injected once over one minute

Also known as: Normal Saline

Functional Dyspepsia: Placebo Then Secretin; Functional Dyspepsia: Secretin Then Placebo; Healthy Controls: Placebo Then Secretin; Healthy Controls: Secretin Then Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 \[i.e., tubal ligation, hysterectomy, or post-menopausal (defined as a minimum of one year since the last menstrual period)\].

You may not qualify if:

• 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

Sponsors & Collaborators

• Mayo Clinic: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Publications (1)

• 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.

  PMID: 32036693 RESULT

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Dyspepsia

Interventions

Secretin; Saline Solution

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptide Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Nerve Tissue Proteins; Proteins; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Michael Camilleri, MD
• Organization: Mayo Clinic

camilleri.michael@mayo.edu

507-266-2305

Study Officials

• Michael Camilleri

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Blinded
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Principal Investigator

Study Record Dates

• First Submitted: July 16, 2018
• First Posted: August 7, 2018
• Study Start: November 7, 2018
• Primary Completion: July 1, 2019
• Study Completion: August 1, 2019
• Last Updated: June 11, 2020
• Results First Posted: June 11, 2020

Record last verified: 2020-06

Locations

US (1)