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

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


Eligibility Criteria:
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