Overview
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
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