Clinical trial NCT06213948: Elucidating Mechanisms That Underlie the Symptomatology of Functional Dyspepsia Using Novel Techniques and Its Therapeutic Validation Using Neuromodulators
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Functional Disorder of Stomach
Healthy
Keywords: Functional dyspepsia
Gastric accommodation
Gastric emptying
Micro inflammation
Lead sponsor: Universiti Sains Malaysia
Sponsor class: OTHER
Collaborators: name: Ministry of Higher Education, Malaysia
First posted: 2024-01-19
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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

Primary outcomes:
measure: Gastric volume (fasting and postprandial)
timeFrame: Fasting, 10-min. postprandial
measure: Gastric emptying profile (4 hours)
timeFrame: Immediately after test meal ingestion, up to 4 hours postprandial
measure: Intragastric pressure
timeFrame: Fasting, up to 30-min. postprandial after reaching maximum tolerated volume
Secondary outcomes:
measure: Satiation
timeFrame: Fasting, up to 30-min. postprandial after reaching maximum tolerated volume
measure: Upper gastrointestinal symptoms
timeFrame: Fasting, up to 30-min. postprandial after reaching maximum tolerated volume
Other outcomes:
measure: Standardized Uptake Value (stomach)
timeFrame: Fasting and 10-min. postprandial
Locations:
city: Kota Bharu
country: Malaysia
facility: Hospital Universiti Sains Malaysia
state: Kelantan
Study officials:
affiliation: Universiti Sains Malaysia
name: Nashrulhaq Tagiling, MSc
role: PRINCIPAL_INVESTIGATOR
References: