Neuroregulators for the Treatment of Diseases Associated With Esophageal-brain-gut Axis Communication Abnormalities.

NCT06778824 | Recruiting

• 1 other identifier: IRB112-201-A
• Study Type: interventional
• Target: 610
• Locations: 1 country
• Sites: 1

Brief Summary

Gastroesophageal reflux disease (GERD) poses a challenging medical condition to manage, with up to 40% of patients showing refractory to standard medical intervention, which usually begins with a proton pump inhibitor (PPI). Among these cases, esophageal disorders of gut-brain interaction (DGBI), such as reflux hypersensitivity and functional heartburn, or GERD patients with concurrent occurrences of these conditions, constitute more than 90% of the patients who did not respond to twice-daily PPI treatment. Esophageal visceral hypersensitivity and hypervigilance are the two pathways that drive esophageal DGBI and symptoms. The Rome IV esophageal disorders, encompassing functional chest pain, functional heartburn, globus, functional dysphagia, and reflux hypersensitivity, are defined by present with symptoms originating from the esophagus without detectable evidence of structural, inflammatory, or motor disorders. Diagnosing esophageal DGBI necessitates testing involving endoscopy, pH-impedance monitoring, and high-resolution manometry. Neuromodulators form the basis of the pharmacological strategy for managing various esophageal DGBI and symptoms, modulating both peripheral and central hyperalgesia. Increasing evidence supports the use of brain-gut behavioral therapies, such as gut-directed hypnotherapy and cognitive behavior therapy, as effective treatments for a variety of DGBIs. However, the efficacy of neuromodulators in treating esophageal DGBI and related symptoms remains largely unexplored. The primary objective of this study is to examine the efficacy of neuromodulators in managing esophageal DGBI. Additionally, investigators will explore various classes of neuromodulators and subtypes of esophageal DGBI to ascertain whether there are differing levels of effectiveness across these conditions. The findings from this study will contribute to a better understanding of the pathophysiology of esophageal DGBI and GERD with refractory symptoms. These clinical insights may then offer valuable guidance for future therapeutic approaches in DGBI patients who experience esophageal symptoms and do not respond to PPI treatment.

Conditions

Gut-Brain Disorders; GERD Without Erosive Esophagitis

Keywords

gastroesophageal reflux disease; disorders of gut-brain interaction; neuromodulators

Outcome Measures

Primary Outcomes (15)

• Gastroesophageal Reflux Disease Questionnaire（GERDQ）

  Each participant will undergo a questionnaire assessment upon entering the study, and another questionnaire assessment will be conducted at the end of the 12-week treatment period.

• PROMIS Gastroesophageal Reflux Disease Questionnaire（PROMIS GERD）

  Each participant will undergo a questionnaire assessment upon entering the study, and another questionnaire assessment will be conducted at the end of the 12-week treatment period.

• Disease symptom index(DSI)

  Each participant will undergo a questionnaire assessment upon entering the study, and another questionnaire assessment will be conducted at the end of the 12-week treatment period.

• Reflux Symptom Index(RSI)

  Each participant will undergo a questionnaire assessment upon entering the study, and another questionnaire assessment will be conducted at the end of the 12-week treatment period.

• The Brief Esophageal Dysphagia Questionnaire(BEDQ)

  Each participant will undergo a questionnaire assessment upon entering the study, and another questionnaire assessment will be conducted at the end of the 12-week treatment period.

• Esophageal Hypervigilance and Anxiety Scale(EHAS)

  Each participant will undergo a questionnaire assessment upon entering the study, and another questionnaire assessment will be conducted at the end of the 12-week treatment period.

• Visceral sensitivity index(VSI)

  Each participant will undergo a questionnaire assessment upon entering the study, and another questionnaire assessment will be conducted at the end of the 12-week treatment period.

• Pittsburgh Sleep Quality Index(PSQI)

  Each participant will undergo a questionnaire assessment upon entering the study, and another questionnaire assessment will be conducted at the end of the 12-week treatment period.

• Taiwanese Depression Questionnaire(TDQ)

  Each participant will undergo a questionnaire assessment upon entering the study, and another questionnaire assessment will be conducted at the end of the 12-week treatment period.

• The State-Trait Anxiety Inventory(STAI)

  Each participant will undergo a questionnaire assessment upon entering the study, and another questionnaire assessment will be conducted at the end of the 12-week treatment period.

• Functional dyspepsia(FD)

  Each participant will undergo a questionnaire assessment upon entering the study, and another questionnaire assessment will be conducted at the end of the 12-week treatment period.

• Irritable bowel syndrome questionnaire(IBS)

  Each participant will undergo a questionnaire assessment upon entering the study, and another questionnaire assessment will be conducted at the end of the 12-week treatment period.

• Short-form-12-health-survey-questionnaire(SF-12)

  Each participant will undergo a questionnaire assessment upon entering the study, and another questionnaire assessment will be conducted at the end of the 12-week treatment period.

• Northwest Esophageal Quality of Life Scale(NEQOL)

  Each participant will undergo a questionnaire assessment upon entering the study, and another questionnaire assessment will be conducted at the end of the 12-week treatment period.

• Global Symptom Severity Questionnaire(GSS)

  Each participant will undergo a questionnaire assessment upon entering the study, and another questionnaire assessment will be conducted at the end of the 12-week treatment period.

Study Arms (3)

tricyclic antidepressant, TCA

EXPERIMENTAL

The main component of tricyclic antidepressants (TCA) is imipramine HCL. Imipramine has various pharmacological effects, including alpha-adrenergic antagonism, antihistamine activity, anticholinergic effects, and blockade of 5-HT3 receptors. The exact mechanism of imipramine's antidepressant action is unknown, but it may primarily involve the inhibition of the reuptake of norepinephrine (NA) and serotonin (5-HT), without including a stimulatory effect on the central nervous system. Indications/Expected Uses: Depression and nocturia.

Drug: Imipramine Pill

selective serotonin reuptake inhibitor, SSRI

EXPERIMENTAL

The mechanism of action of the selective serotonin reuptake inhibitor (SSRI) sertraline is believed to be related to the inhibition of serotonin (5-HT) reuptake in the central nervous system. Clinical studies have confirmed that when humans receive appropriate doses of sertraline, it can inhibit the reuptake of serotonin into platelets in the body. Indications/Expected Uses: Depression, obsessive-compulsive disorder (OCD), panic disorder, post-traumatic stress disorder (PTSD), social anxiety disorder, and premenstrual dysphoric disorder (PMDD).

Drug: Zoloft 50Mg Tablet

proton-pump inhibitor, PPI

EXPERIMENTAL

Proton-pump inhibitors (PPIs) inhibit gastric acid secretion by specifically targeting the (H+, K+)-ATPase enzyme system on the surface of gastric parietal cells. This enzyme system can be considered an acid (proton) pump within the parietal cells, blocking the final step of gastric acid production. As a result, they are classified as gastric acid pump inhibitors, effectively reducing both basal and stimulated gastric acid secretion, independent of stimulation. Lansoprazole does not possess anticholinergic or histamine H2-receptor antagonist activity. Indications/Expected Uses: Treatment of gastric ulcers, duodenal ulcers, gastroesophageal reflux disease (GERD) with erosive esophagitis, and management of symptoms related to GERD. It is also used in Zollinger-Ellison syndrome, in combination with antibiotic treatment for Helicobacter pylori-related peptic ulcers, and for the treatment of gastric ulcers induced by NSAIDs.

Drug: Takepron

Interventions

Takepron DRUG

Participants are expected to take a proton-pump inhibitor (PPI) for 12 weeks, with a dosage of 30 mg taken once a day.

Also known as: Takepron ® OD Tablets 15．30mg

proton-pump inhibitor, PPI

Zoloft 50Mg Tablet DRUG

Participants are expected to take a selective serotonin reuptake inhibitor (SSRI) for 12 weeks, with a dosage of 50 mg taken once a day.

Also known as: ZOLOFT Film Coated Tablets 50 mg

selective serotonin reuptake inhibitor, SSRI

Imipramine Pill DRUG

Participants are expected to take tricyclic antidepressants (TCA) for 12 weeks, with a dosage of 25 mg taken twice a day.

Also known as: Tone F.C. Tablets 25mg"MEIDER"(lmipramine hydrochloride)

tricyclic antidepressant, TCA

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18 and 75 years, with clear consciousness and willingness to sign the informed consent form.
• Subjects with chronic esophageal symptoms related to disorders of the brain-gut axis communication (such as heartburn, acid reflux, sensation of a foreign body in the throat, difficulty swallowing, and chest pain or discomfort).

You may not qualify if:

• Esophageal strictures, or history of surgery on the esophagus, gastrointestinal tract, or throat.
• Structural esophageal diseases (such as diverticula, esophageal rings, etc.), infectious esophagitis, erosive esophagitis, eosinophilic esophagitis.
• Non-erosive gastroesophageal reflux disease or significant esophageal motility disorders.
• History of or current diagnosis of malignancies in the esophagus, gastrointestinal tract, or other organs.
• Significant endocrine or rheumatic immune diseases that may affect gastrointestinal motility.
• Continuous use of medications that may affect esophageal motility within the past month (such as anticholinergics, opioid-like agents, nitrates, calcium channel blockers, etc.).
• Use of or currently taking antidepressants, selective serotonin reuptake inhibitors, or other psychotropic medications within the past three months.
• Pregnant or breastfeeding women.
• Individuals with mental illness or those who are unable to cooperate.
• Known allergy to tricyclic antidepressants.
• Known allergy to selective serotonin reuptake inhibitors.
• Known allergy to any component of proton pump inhibitors.

Sponsors & Collaborators

• Hualien Tzu Chi General Hospital: lead

Study Sites (1)

Hualien Tzu Chi Hospital,Buddhist Tzu Chi Medical Foundation

Hualien City, 970, Taiwan

RECRUITING

MeSH Terms

Conditions

Gastroesophageal Reflux

Interventions

Lansoprazole; Sertraline; Tablets; Imipramine

Condition Hierarchy (Ancestors)

Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; 1-Naphthylamine; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Dosage Forms; Pharmaceutical Preparations; Dibenzazepines; Heterocyclic Compounds, 3-Ring

Study Officials

• Gastroenterology attending physician Lei Wei-Yi

  staff

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gastroenterology attending physician Lei Wei-Yi

CONTACT

886-3-8561825ext13226; hlmweb@tzuchi.com.tw

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: HualienTCGH

Study Record Dates

• First Submitted: January 5, 2025
• First Posted: January 16, 2025
• Study Start: April 2, 2024
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: January 27, 2025

Record last verified: 2025-01

Locations

TW (1)