Cognitive-behavioral Therapy for the Diseases Associated With Esophageal-brain-gut Axis Communication Abnormalities.

NCT06939465 | Recruiting

• 1 other identifier: TCRD113-042
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Gastroesophageal reflux disease (GERD) is a challenging gastrointestinal disorder, and proton pump inhibitors (PPIs) are typically the first line of treatment. However, up to 40% of GERD patients experience little to no relief or only partial relief of their symptoms after receiving PPI therapy. Among these patients, who do not respond to high-dose PPIs taken twice daily, more than 90% exhibit conditions related to brain-gut axis communication disorders, such as esophageal hypersensitivity and functional heartburn. Visceral hypersensitivity and esophageal hypervigilance are the two key causes of esophageal symptoms in this group of patients. According to the Rome IV consensus on esophageal disorders, five categories are identified: functional chest pain, functional heartburn, globus sensation, functional dysphagia, and esophageal hypersensitivity. The diagnostic criteria state that patients must have chronic esophageal symptoms, and any structural, inflammatory, or motility abnormalities must be excluded. Therefore, diagnosing brain-gut axis communication disorders in the esophagus requires upper gastrointestinal endoscopy, esophageal pH-impedance testing, and high-resolution esophageal manometry. Neuromodulators, which regulate peripheral and central pain sensitivity, are a cornerstone of pharmacological treatment for brain-gut axis communication disorders and associated symptoms. Additionally, growing evidence supports the use of brain-gut axis behavioral therapies, such as gut-directed hypnotherapy and cognitive behavioral therapy (CBT), to effectively treat these disorders. However, research on neuromodulators and CBT in brain-gut axis communication disorders remains limited, and their efficacy is still unclear. The aim of this study is to investigate the effectiveness and role of CBT in treating brain-gut axis communication disorders. The information gained from this research will help clarify the pathophysiological mechanisms related to brain-gut axis communication abnormalities and refractory GERD symptoms. Furthermore, the findings will guide the development of effective treatment strategies for patients with brain-gut axis communication disorders who do not respond to PPI therapy in clinical practice.

Conditions

Gut-Brain Disorders; GERD Without Erosive Esophagitis

Keywords

gastroesophageal reflux disease; disorders of gut-brain interaction; cognitive behavior therapy

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. The minimum score of the questionnaire is 0 and the maximum score is 18. The higher the score, the worse the gastroesophageal reflux symptoms.

  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. The minimum score of the questionnaire is 0 and the maximum score is 52. The higher the score, the worse the gastroesophageal reflux symptoms.

  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. The minimum score of the questionnaire is 0 and the maximum score is 16. The higher the score, the worse the gastroesophageal reflux symptoms.

  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 minimum score of the questionnaire is 0 and the maximum score is 45. The higher the score, the worse the gastroesophageal reflux symptoms.

  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. The lowest score of the questionnaire is 0 and the highest score is 40. The higher the score, the more severe the dysphagia.

  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. The lowest score of the questionnaire is 0 and the highest score is 60. The higher the score, the more severe the esophageal hypervigilance and anxiety.

  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. The lowest score of the questionnaire is 0 and the highest score is 75. The higher the score, the higher the visceral sensitivity.

  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. The lowest score of the questionnaire is 0 and the highest score is 21. The higher the score, the worse the sleep quality.

  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 lowest score of the questionnaire is 0 and the highest score is 54. The higher the score, the higher the depression index.

  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. The lowest score of the questionnaire is 1 and the highest score is 80. The higher the score, the more obvious the anxiety trait.

  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.

• Illness Cognition Questionnaire (ICQ)

  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 lowest score of the questionnaire is 1 and the highest score is 72. The higher the score, the higher the level of disease awareness.

  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. The results of the SF-12 health scale mainly include two total scores: physical health total score (PCS) and mental health total score (MCS). These two scores are used to measure an individual's health status in these two aspects. 1. \*\*Physical Health Score (PCS) and Mental Health Score (MCS)\*\* are usually expressed as standardized scores with a mean of 50 and a standard deviation of 10. 2. A higher score indicates better health, whereas a lower score indicates worse health.

  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. The lowest score of the questionnaire is 0 and the highest score is 56. The higher the score, the worse the esophageal quality of life.

  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. The minimum score of the questionnaire is 0 and the maximum score is 100. The higher the score, the worse the gastroesophageal reflux symptoms.

  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.

• Heart rate variability(HRV)

  Participants will undergo heart rate variability measurement before receiving treatment, and another heart rate variability measurement will be conducted after week 12 of the study.

  Participants will undergo heart rate variability measurement before receiving treatment, and another heart rate variability measurement will be conducted after week 12 of the study.

Study Arms (2)

Cognitive behavioral therapy (CBT)

ACTIVE COMPARATOR

Cognitive Behavioral Therapy (CBT) will be implemented according to the following steps: (1) Psychoeducation and beginning of tracking; (2) Introduction to heart rate variability and breathing; (3) Cognitive restructuring and breathing application; (4) Cognitive defusion and behavioral experiments; (5) Coping strategies for problem-focused and emotion-focused approaches; (6) Conclusion of therapy and relapse prevention.

Behavioral: Cognitive Behavioral Therapy (CBT)

Lifestyle management (sham control)

SHAM COMPARATOR

Lifestyle management (sham control) will be implemented according to the following steps: (1) Psychoeducation and beginning of tracking; (2) Dietary habits: What, when, where, and why; (3) Changing my diet: Strategies and barriers; (4) Lifestyle factors: Alcohol, smoking, and sugar; (5) Lifestyle factors: Sleep and exercise; (6) Conclusion of therapy and relapse prevention.

Behavioral: Lifestyle management (sham control)

Interventions

Cognitive Behavioral Therapy (CBT) BEHAVIORAL

The participants will undergo a 6-week cognitive behavioral therapy (CBT) guided by a psychologist, with one session per week, each lasting 1 hour.

Cognitive behavioral therapy (CBT)

Lifestyle management (sham control) BEHAVIORAL

The participants will undergo a 6-week lifestyle management (sham control) guided by a psychologist, with one session per week, each lasting 1 hour.

Lifestyle management (sham control)

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, Taiwan

RECRUITING

MeSH Terms

Conditions

Gastroesophageal Reflux

Interventions

Cognitive Behavioral Therapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities

Central Study Contacts

Wei-Yi Lei Gastroenterology attending physician

CONTACT

+88638561825; hlmweb@tzuchi.com.tw

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Gastroenterology attending physician

Study Record Dates

• First Submitted: April 15, 2025
• First Posted: April 22, 2025
• Study Start: April 2, 2024
• Primary Completion: April 24, 2025
• Study Completion: December 31, 2025
• Last Updated: April 29, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)