Evaluation of the Clinical Course of Non-erosive Reflux Disease and Assessment of the Esophageal Mucosa Resistance Before and After Complex Therapy
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Assess the intensity of symptoms
研究概览
简要总结
GERD is characterized by a high prevalence (about 13.3%) and is associated with a deterioration in the quality of life, as well as an increased risk of esophageal adenocarcinoma and a rise in the number of refractory cases. NERD is one of the forms of GERD, accounting for about 70% of all cases, and is characterized by symptoms that reduce the quality of life. Although proton pump inhibitors (PPIs) are the basic therapy for NERD, up to 40% of patients do not achieve an optimal clinical outcome. GERD symptoms seriously affect the quality of life and performance, which makes the study of complex therapy relevant. One of the mechanisms of GERD is a violation of the barrier function of the esophageal mucosa, associated with an increase in epithelial permeability due to the dysfunction of intercellular junction proteins, such as claudins and occludin. The study of methods to increase tissue resistance and cytoprotection, together with acid-suppressive therapy, is a promising direction, especially for refractory forms of NERD. It is relevant to study the complex treatment of NERD in order to change the clinical course of the disease and improve the tissue resistance of the esophageal mucosa. These hypotheses and theses emphasize the need for a comprehensive approach to the treatment of NERD and a research focus on improving the barrier functions of the esophagus
详细描述
The relevance of gastroesophageal reflux disease (GERD) in clinical practice today is associated with its high prevalence, significant reduction in patients' quality of life, increased risk of esophageal adenocarcinoma, and a growing number of cases resistant to standard antisecretory therapy. Recent estimates indicate a global prevalence of GERD at approximately 13.3%. Non-erosive reflux disease (NERD) is a GERD phenotype characterized by reflux-induced symptoms that impair quality of life without esophageal mucosal erosions detectable by conventional endoscopy, and occurring in the absence of ongoing antisecretory therapy. According to the literature, about 70% of GERD cases are attributed to the NERD. Proton pump inhibitors (PPIs) are the cornerstone of NERD therapy; however, studies reveal that up to 40% of patients do not achieve optimal clinical outcomes with PPI therapy. Notably, the significant impact of GERD symptoms on patients' quality of life and work capacity represents a crucial medical and social issue, underscoring the relevance of exploring combination therapies and addressing the key pathogenetic factors of the disease.
One of the leading mechanisms in the development of the disease is the impaired barrier function of the esophageal mucosa, a critical aspect of which is increased epithelial permeability due to disrupted intercellular resistance resulting from the dysfunction of tight junction proteins. Major proteins involved in intercellular adhesion include claudin-1, claudin-3, claudin-4, and occludin, whose primary cytoprotective role is to prevent the diffusion of H+ ions and other active luminal substances into the esophageal mucosa. Investigating ways to enhance tissue resistance and cytoprotection by targeting the barrier function of the esophageal mucosa, alongside standard acid-suppressive therapy, represents a promising approach in NERD treatment, particularly for refractory cases.
Thus, it is pertinent to study the role of comprehensive treatment of NERD in altering the clinical course of the disease and the tissue resistance parameters of the esophageal mucosa.
2. Novelty of the Proposed Topic Based on Literature Sources and Patent Documentation
The novelty of this study lies in the comprehensive examination of the following parameters:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The availability of written informed consent from the patient to participate in the study.
- •Patients aged over 18 years.
- •Gender: both men and women.
- •The patient must be able to independently fill out questionnaires and assess their condition using scales.
- •A confirmed diagnosis of non-erosive reflux disease.
排除标准
- •The voluntary withdrawal of consent to participate in the study by the patient.
- •The patient experienced a serious adverse event, the relationship of which to the study drug is classified as definite, probable, or possible.
- •The patient is receiving/requires additional treatment that may affect the efficacy parameters being studied.
- •Protocol violations that, in the opinion of the investigator, are significant for the results of the clinical trial.
结局指标
主要结局
Assess the intensity of symptoms
时间窗: Before treatment and 4 weeks after the start of therapy
Assess the intensity of symptoms using a SYMPTOM INTENSITY QUESTIONNAIRE ON THE LIKERT SCALE (including intensity of heartburn, regurgitation, chest pain, belching, cough, and sensation of mucus in the throat). 5-point scale: 1. Symptom absent 2. Mild symptom, occasionally present 3. Moderate symptom 4. Severe symptom 5. Persistent symptom
Examine the inflammatory changes in the esophageal mucosa.
时间窗: Before treatment and again 4 weeks after the start of therapy.
Examine the inflammatory changes in the esophageal mucosa (such as dilated intercellular spaces, intraepithelial eosinophils, intraepithelial neutrophils, intraepithelial mononuclear cells, basal cell hyperplasia, elongation of papillae in the lamina propria, and spongiosis) through morphological examination.
Study the expression of tight junction proteins in esophageal mucosa.
时间窗: Before treatment and 4 weeks after the start of therapy.
Study the expression of tight junction proteins in esophageal mucosa samples by immunohistochemistry.
次要结局
- Assess the сhange in Acid Exposure Time (%)(Before treatment and 4 weeks after the start of therapy)
- Change in Total Number of Gastroesophageal Reflux Episodes(Before treatment and 4 weeks after the start of therapy)
- Change in Number of Proximal Reflux Episodes(Before treatment and 4 weeks after the start of therapy)
- Change in Composition of Reflux Episodes (Liquid, Mixed, Gas)(Before treatment and 4 weeks after the start of therapy)
- Change in Mean Nocturnal Baseline Impedance (MNBI) (Ohms)(Before treatment and 4 weeks after the start of therapy)
- Change in Lower Esophageal Sphincter Pressure (mmHg)(Before treatment and 4 weeks after the start of therapy)
- Change in Distal Esophageal Contractile Integral (mmHg · cm · sec)(Before treatment and 4 weeks after the start of therapy)
- Change in Number of Transient Lower Esophageal Sphincter Relaxations (TLESRs)(Before treatment and 4 weeks after the start of therapy)