Elucidating Mechanisms That Underlie the Symptomatology of Functional Dyspepsia Using Novel Techniques and Its Therapeutic Validation Using Neuromodulators

Elucidating Mechanisms That Underlie Symptomatology of Functional Dyspepsia Using Novel Imaging Technique of SPECT/CT, MRI, High-Resolution Manometry and Biomarkers; and the Therapeutic Validation of Elucidated Mechanisms Using Neuromodulator Compounds

The goal of this study is to investigate the mechanisms of impaired gastric accommodation and emptying, dysfunctional duodenum, and micro-inflammation using novel imaging techniques of SPECT/CT, gastric emptying scintigraphy, MRI, high-resolution manometry, and inflammatory biomarkers, as well as to validate these mechanisms using a therapeutic trial of neuromodulator (mirtazapine) in functional dyspepsia (FD) and health. The main objective[s] it aims to answer are:

• to investigate impaired gastric accommodation through SPECT/CT imaging and high-resolution manometry findings of the stomach fundus.
• to investigate impaired gastric emptying through gastric emptying scintigraphy
• to investigate for a dysfunctional duodenum through MRI imaging of the duodenum.
• to investigate micro-inflammation through SPECT/CT standard uptake value (SUV), inflammatory biomarkers (eosinophils, mast cells, IL-6, IL-10) and mucosal barrier marker (E-cadherin).
• to investigate if a therapeutic trial of a neuromodulator agent, mirtazapine, ameliorates symptoms of FD through improvement in impaired gastric accommodation.

For objectives 1-4, FD patients and healthy volunteers will be consecutively recruited, and all will undergo SPECT/CT, MRI, high-resolution manometry and biomarkers, and data acquired from these tests will be analyzed. For objective 5, the enrolled participants who did all baseline tests/markers are given mirtazapine for four weeks, and all tests/markers, except biomarkers and MRI, are repeated at the end of the trial

Study Overview

• Status: Recruiting
• Conditions: Healthy; Functional Disorder of Stomach
• Intervention / Treatment: Drug: Mirtazapine 15 MG

• Study Type: Interventional
• Enrollment (Estimated): 54
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Norazlina Mat Nawi, MD, MMed; Phone Number: +609-7676684; Email: norazlina@usm.my
• Study Contact Backup: Name: Lee Yeong Yeh, MD, PhD; Phone Number: +609-7673974; Email: yylee@usm.my

Study Locations

• Malaysia
  • Kelantan
    • Kota Bharu, Kelantan, Malaysia, 16150
      • Recruiting
      • Hospital Universiti Sains Malaysia
      • Contact: Nashrulhaq Tagiling, MSc; Phone Number: +609-7676684; Email: nashrulhaq17@student.usm.my
      • Principal Investigator: Nashrulhaq Tagiling, MSc
      • Sub-Investigator: Norazlina Mat Nawi, MD, MMed
      • Sub-Investigator: Lee Yeong Yeh, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria (Healthy):

• Age 18 and above, up to 65 years old
• No current GI symptoms (as assessed by history taking during screening and based on the investigators' collective judgement)
• No previous GI illness (as determined by clinically significant findings from medical history taking and vital signs)
• No chronic medical illness e.g., chronic neurological, cardiovascular, pulmonary, endoscirne and hematological disorders, as well as psychiatric disorders

Exclusion Criteria (Healthy):

• BMI of less than 18.50 and more than 29.99
• Had undergone any abdominal surgery except appendicectomy, tubal ligation, or Caesarean section
• Females that are pregnant, expecting to become pregnant during the study period, or breastfeeding
• Aversion to test meals
• Use of medications that may alter gastrointestinal function and motility
• Contraindication for MRI examination e.g., cardiac pacemaker, ferromagnetic implants, claustrophobia

Inclusion Criteria (FD patients):

• Age 18 and above, up to 65 years old
• Satisfy the diagnosis of FD as per Rome IV criteria
• Absence of organic disorders that explain dyspepsia in patients such as autoimmune disease, inflammatory disease or brain trauma
• No other chronic medical illnesses (including chronic neurological, cardiovascular, pulmonary, endocrine and hematological disorders) and psychiatric disorders

Exclusion Criteria (FD patients):

• Positive Helicobacter pylori test
• Presence of esophagitis, gastric atrophy, heartburn as predominant symptom, history of peptic ulcer or major abdominal surgery
• Medications that potentially affects gastrointestinal motility or sensitivity (eg: acid suppressant, prokinetics, corticosteroids, NSAIDs and analgesics apart from paracetamol)
• Aversion to test meals
• Recent trauma to the abdomen
• Patients on antipsychotic or antidepressant in the last 6 weeks
• Contraindication for MRI examination e.g., cardiac pacemaker, ferromagnetic implants, claustrophobia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy	Drug: Mirtazapine 15 MG; Mirtazapine; Commercial name: Remeron® SolTab; Pharmaceutical form: film-coated tablets (15 mg)
Experimental: Functional Dyspepsia	Drug: Mirtazapine 15 MG; Mirtazapine; Commercial name: Remeron® SolTab; Pharmaceutical form: film-coated tablets (15 mg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gastric volume (fasting and postprandial)	SPECT/CT volumetry	Fasting, 10-min. postprandial
Gastric emptying profile (4 hours)	Gastric emptying scintigraphy	Immediately after test meal ingestion, up to 4 hours postprandial
Intragastric pressure	High-resolution manometry	Fasting, up to 30-min. postprandial after reaching maximum tolerated volume

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Satiation	Satiation scale	Fasting, up to 30-min. postprandial after reaching maximum tolerated volume
Upper gastrointestinal symptoms	Visual analog scale	Fasting, up to 30-min. postprandial after reaching maximum tolerated volume

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Standardized Uptake Value (stomach)	SPECT/CT quantitative imaging	Fasting and 10-min. postprandial

Collaborators and Investigators

• Sponsor: Universiti Sains Malaysia
• Collaborators: Ministry of Higher Education, Malaysia
• Investigators: Principal Investigator: Nashrulhaq Tagiling, MSc, Universiti Sains Malaysia

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2021
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: January 9, 2024
• First Submitted That Met QC Criteria: January 9, 2024
• First Posted (Estimated): January 19, 2024

Study Record Updates

• Last Update Posted (Estimated): January 19, 2024
• Last Update Submitted That Met QC Criteria: January 9, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Gastric emptying; Gastric accommodation; Functional dyspepsia; Micro inflammation
• Additional Relevant MeSH Terms: Digestive System Diseases; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Dyspepsia; Stomach Diseases; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Antidepressive Agents; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Anti-Anxiety Agents; Serotonin 5-HT3 Receptor Antagonists; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Adrenergic alpha-Antagonists; Adrenergic alpha-2 Receptor Antagonists; Mirtazapine
• Other Study ID Numbers: USM/JEPeM/20120624

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: IPD sharing has yet to be discussed thoroughly with co-investigators.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No