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Effect of Secretin in Functional Dyspepsia and Healthy Subjects

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ClinicalTrials.gov Identifier: NCT03617861
Recruitment Status : Completed
First Posted : August 7, 2018
Results First Posted : June 11, 2020
Last Update Posted : June 11, 2020
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Michael Camilleri, MD, Mayo Clinic

Tracking Information
First Submitted Date  ICMJE July 16, 2018
First Posted Date  ICMJE August 7, 2018
Results First Submitted Date  ICMJE May 15, 2020
Results First Posted Date  ICMJE June 11, 2020
Last Update Posted Date June 11, 2020
Actual Study Start Date  ICMJE November 7, 2018
Actual Primary Completion Date July 1, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 15, 2020)
  • Maximum Satiation [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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'.
Original Primary Outcome Measures  ICMJE
 (submitted: July 31, 2018)
  • To compare the effects of secretin and placebo on satiation [ Time Frame: 60 minutes ]
    To compare effects of secretin vs. saline on milliliters of Ensure needed to reach fullness and maximum tolerated volume in each group of participants and to assess difference in effects of secretin on satiation in healthy versus functional dyspepsia participants
  • To compare the effects of secretin and placebo on fasting gastric volume [ Time Frame: 15 minutes ]
    To compare effects of treatment in each group of participants and to assess difference in effects of secretin on fasting gastric volume (milliliters) in healthy versus functional dyspepsia participants
  • To compare the effects of secretin and placebo on Gastric accommodation [ Time Frame: 30 minutes ]
    To compare effects of treatment in each group of participants and to assess effects of secretin vs. saline on difference in gastric accommodation after ingestion of 300 mL of Ensure
  • To compare the effects of secretin and placebo on Gastric emptying [ Time Frame: 60 minutes ]
    To compare effects of treatment in each group of participants and to assess effects of secretin vs. saline on gastric emptying of Ensure in the 2 groups of participants
  • To compare the effects of secretin and placebo on Postprandial symptoms [ Time Frame: 90 minutes ]
    To compare effects of secretin vs. saline on symptoms response scores to nausea, fullness, bloating and abdominal pain over 90 minutes after ingesting maximum tolerated volume, and to assess effects of secretin vs. saline on symptoms in the 2 groups of participants
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effect of Secretin in Functional Dyspepsia and Healthy Subjects
Official Title  ICMJE Effect of Secretin on Gastric Accommodation, Emptying and Post-nutrient Challenge Symptoms in Functional Dyspepsia and Healthy Subjects
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Masking Description:
Blinded
Primary Purpose: Treatment
Condition  ICMJE
  • Dyspepsia
  • Healthy
Intervention  ICMJE
  • Drug: Human Secretin
    Injected once over one minute
    Other Name: ChiRhoStim
  • Drug: Placebo
    Injected once over one minute
    Other Name: Normal Saline
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Human Secretin
    • Drug: Placebo
  • 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.
    Interventions:
    • Drug: Human Secretin
    • Drug: Placebo
  • 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.
    Interventions:
    • Drug: Human Secretin
    • Drug: Placebo
  • 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.
    Interventions:
    • Drug: Human Secretin
    • Drug: Placebo
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 15, 2020)
20
Original Estimated Enrollment  ICMJE
 (submitted: July 31, 2018)
30
Actual Study Completion Date  ICMJE August 1, 2019
Actual Primary Completion Date July 1, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03617861
Other Study ID Numbers  ICMJE 18-003744
R01DK115950 ( U.S. NIH Grant/Contract )
R01DK122280 ( U.S. NIH Grant/Contract )
UL1TR002377 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Michael Camilleri, MD, Mayo Clinic
Study Sponsor  ICMJE Mayo Clinic
Collaborators  ICMJE National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators  ICMJE
Principal Investigator: Michael Camilleri Mayo Clinic
PRS Account Mayo Clinic
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP