Clinical trial NCT03617861: Effect of Secretin in Functional Dyspepsia and Healthy Subjects
Official title: Effect of Secretin on Gastric Accommodation, Emptying and Post-nutrient Challenge Symptoms in Functional Dyspepsia and Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Dyspepsia
Healthy
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2018-08-07
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Maximum Satiation
timeFrame: 60 minutes
measure: Fasting Gastric Volume
timeFrame: Baseline
measure: Postprandial Volume
timeFrame: 15 minutes
measure: Change in Gastric Accommodation
timeFrame: Baseline, 30 minutes
measure: Gastric Emptying
timeFrame: 30 minutes
measure: Change in Postprandial Symptoms
timeFrame: Baseline, 30 minutes
Secondary outcomes:
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Michael Camilleri
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.