Efficacy of Gut-Brain Neuromodulators in the Treatment of Gastroesophageal Reflux Disease

A Randomized Controlled Study on the Efficacy and Safety of Gut-Brain Neuromodulators in Patients With Gastroesophageal Reflux Disease

Gastroesophageal reflux disease (GERD) is a common chronic digestive system disorder with a high prevalence and a notably increasing trend. It imposes significant costs in terms of treatment expenses and impacts patients' quality of life. Acid suppression remains the primary treatment for GERD. However, numerous clinical studies have shown that 20-30% of patients still exhibit poor response to proton pump inhibitors (PPIs) even after completing a standard course of acid-suppressive therapy. Many studies have demonstrated that the incidence of abnormal psychological conditions, such as anxiety, depression, and obsessive-compulsive disorder, is higher in GERD patients compared to the general population. Current international consensus acknowledges that the application of psychosomatic medicine principles and the use of neuromodulators can effectively alleviate symptoms in patients with gut-brain interaction disorders. Nevertheless, with the growing emphasis on digestive-psychosomatic-holistic medicine in clinical practice and the deepening of research on "gut-brain interactions," recent studies in the field of psycho-gastroenterology have challenged the notion that psychological processes are unique to gut-brain interaction disorders. Instead, these processes may play a universal role in symptom generation across the entire spectrum of GERD. Previous experiments have confirmed that Flupentixol-Melitracen (FM) can improve symptoms in GERD patients with a low incidence of adverse reactions. Therefore, we aim to verify the efficacy and safety of neuromodulators in patients with GERD, reduce healthcare costs, and provide new insights for optimizing treatment strategies for GERD patients in the future.

Study Overview

• Status: Completed
• Conditions: Gastroesophageal Reflux Disease
• Intervention / Treatment: Drug: Flupentixol-Melitracen + Lansoprazole; Drug: Lansoprazole and placebo

• Study Type: Interventional
• Enrollment (Actual): 164
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China
      • Shanghai Jiaotong university，renji hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

- Adults aged 18-70 years with gastroesophageal reflux disease (GERD) meeting diagnostic criteria.

Exclusion Criteria:

• Patients with organic gastrointestinal disorders (e.g., celiac disease, inflammatory bowel disease, history of gastrointestinal malignancies);

Severe dysfunction of major organs (e.g., class IV cardiac dysfunction, hepatic failure, uremia, respiratory failure) or congenital diseases (e.g., hemophilia, Wilson's disease);

Hypersensitivity to study medications;

Patients who are pregnant, lactating, or planning pregnancy;

Use of monoamine oxidase inhibitors (e.g., linezolid or intravenous methylene blue) within the past 5 weeks;

Severe psychological symptoms or cognitive impairment (GAD-7 >15 or PHQ-9 ≥15);

Circulatory failure, central nervous system depression (e.g., acute alcohol, barbiturate, or opioid intoxication), or coma.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients were treated with Flupentixol-Melitracen (FM) plus lansoprazole for 2 weeks	Drug: Flupentixol-Melitracen + Lansoprazole; Flupentixol-Melitracen and Lansoprazole for the treatment of GERD
Placebo Comparator: Patients were treated with placebo plus lansoprazole for 2 weeks	Drug: Lansoprazole and placebo; Placebo and Lansoprazole for GERD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GERD questionnaire (GerdQ)	The GerdQ Scale is a validated tool for assessing gastroesophageal reflux disease (GERD). It includes 6 items evaluating symptom frequency (heartburn, regurgitation), extra-esophageal manifestations, and quality of life impact (e.g., sleep disturbance, medication use) over the past week. Scores range 0-18; ≥8 suggests high GERD likelihood, guiding stepwise treatment (lifestyle changes or PPIs).	Until the end of the study, up to 12 weeks

Collaborators and Investigators

• Sponsor: RenJi Hospital
• Investigators: Principal Investigator: Sheng L Chen, doctor, Shanghai Jiao Tong University School of Medicine，Renji Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2025
• Primary Completion (Actual): August 1, 2025
• Study Completion (Actual): October 30, 2025

Study Registration Dates

• First Submitted: April 18, 2025
• First Submitted That Met QC Criteria: April 18, 2025
• First Posted (Actual): April 25, 2025

Study Record Updates

• Last Update Posted (Actual): November 18, 2025
• Last Update Submitted That Met QC Criteria: November 17, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Esophageal Diseases; Esophageal Motility Disorders; Deglutition Disorders; Gastroesophageal Reflux; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Lansoprazole; flupentixol, melitracen drug combination
• Other Study ID Numbers: RJYYQKLY-04

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No