Exploring Methods for Treating Hypergastrinemia in Patients With Autoimmune Gastritis

Not Applicable

Recruiting

• Conditions: Autoimmune Gastritis

• Registration Number: NCT06272500
• Lead Sponsor: Jianning Yao

Brief Summary

Autoimmune atrophic gastritis (AAG) is an organ-specific autoimmune disease that primarily affects the gastric body and fundus while sparing the antrum. Its characteristics include destruction of gastric wall cells, loss of intrinsic factors, and atrophy of the gastric mucosa. Endoscopic examination reveals features of reverse atrophy, with significant atrophy in the gastric body and fundus, appearing as a mosaic of red and white patches. Currently, AAG is believed to result from a pathological CD4+ T-cell-mediated autoimmune response against the gastric H+/K+-ATPase. CD4+ T lymphocytes target the parietal cells' H+/K+-ATPase, stimulating plasma cells to secrete autoantibodies, including parietal cell antibodies (PCA) and intrinsic factor antibodies (IFA). The former plays a key role in parietal cell destruction and glandular atrophy. AAG is considered a premalignant condition, with the potential development of gastric dysplasia, cancer, and type 1 gastric neuroendocrine tumours (type 1 g-NET).

Gastric neuroendocrine tumors (g-NETs), also known as gastric carcinoids, account for approximately 23% of gastrointestinal and pancreatic neuroendocrine tumors. Clinically, g-NETs are mainly classified into three types. Type III is typically sporadic tumors associated with normal gastrin levels and poor prognosis. Although type 1 g-NETs caused by AAG are usually well-differentiated, studies have reported that 8%-23% of type 1 g-NETs extending into the deep submucosal layer may metastasize to regional lymph nodes or even to the liver. Furthermore, 3% of patients may develop neuroendocrine carcinoma, highlighting the need for appropriate attention.

Due to the destruction of gastric glands (including parietal and chief cells) in AAG patients, there is a deficiency in intrinsic factor, gastric acid, and a decrease in pepsinogen I (PG-I) levels. Insufficient gastric acid secretion leads to a compensatory increase in gastrin secretion by G cells in the gastric antrum, which acts on receptors present in enterochromaffin-like cells (ECL) in the gastric body and fundus, promoting ECL cell proliferation. Prolonged stimulation by hypergastrinemia can result in the development of ECL cell tumors, namely type 1 g-NETs. Considering the close association between type 1 g-NETs and AAG, primarily related to hypergastrinemia resulting from reduced gastric acid secretion, it is hypothesized that supplementation with gastric acid could provide negative feedback regulation of gastrin, reducing the risk of type 1 g-NET development in AAG patients. This study aims to investigate the impact of Betaine hydrochloride(BHCL) on gastrin levels in AAG patients, thus exploring a simple and cost-effective method to reduce the risk of type 1 g-NETs in AAG patients.

Detailed Description

Autoimmune atrophic gastritis (AAG) is an organ-specific autoimmune disease that primarily affects the gastric body and fundus while sparing the antrum. Its characteristics include destruction of gastric wall cells, loss of intrinsic factors, and atrophy of the gastric mucosa. Endoscopic examination reveals features of reverse atrophy, with significant atrophy in the gastric body and fundus, appearing as a mosaic of red and white patches, predominantly white, with flattened and partially disappearing folds and visible blood vessels. Currently, AAG is believed to result from a pathological CD4+ T-cell-mediated autoimmune response against the gastric H+/K+-ATPase. CD4+ T lymphocytes target the parietal cells' H+/K+-ATPase, stimulating plasma cells to secrete autoantibodies, including parietal cell antibodies (PCA) and intrinsic factor antibodies (IFA). The former plays a key role in parietal cell destruction and glandular atrophy, while the latter is the main mechanism underlying vitamin B12 deficiency and pernicious anaemia. AAG is considered a premalignant condition, with the potential development of gastric dysplasia, cancer, and type 1 gastric neuroendocrine tumours (type 1 g-NET).

Gastric neuroendocrine tumors (g-NETs), also known as gastric carcinoids, account for approximately 23% of gastrointestinal and pancreatic neuroendocrine tumors. Clinically, g-NETs are mainly classified into three types. Type I and type II are associated with chronic atrophic autoimmune gastritis\[9\] and gastrinoma-related Zollinger-Ellison syndrome (ZES) leading to hypergastrinemia, while type III is typically sporadic tumors associated with normal gastrin levels and poor prognosis. Although type 1 g-NETs caused by AAG are usually well-differentiated, studies have reported that 8%-23% of type 1 g-NETs extending into the deep submucosal layer may metastasize to regional lymph nodes or even to the liver. Furthermore, 3% of patients may develop neuroendocrine carcinoma, highlighting the need for appropriate attention.

Due to the destruction of gastric glands (including parietal and chief cells) in AAG patients, there is a deficiency in intrinsic factor, gastric acid, and a decrease in pepsinogen I (PG-I) levels. Insufficient gastric acid secretion leads to a compensatory increase in gastrin secretion by G cells in the gastric antrum, which acts on receptors present in enterochromaffin-like cells (ECL) in the gastric body and fundus, promoting ECL cell proliferation. Prolonged stimulation by hypergastrinemia can result in the development of ECL cell tumors, namely type 1 g-NETs. Considering the close association between type 1 g-NETs and AAG, primarily related to hypergastrinemia resulting from reduced gastric acid secretion, it is hypothesized that supplementation with gastric acid could provide negative feedback regulation of gastrin, reducing the risk of type 1 g-NET development in AAG patients. This study aims to investigate the impact of Betaine hydrochloride(BHCL) on gastrin levels in AAG patients, thus exploring a simple and cost-effective method to reduce the risk of type 1 g-NETs in AAG patients.

Study Timeline

• Study Start: 2024-02-01
• Study First Submitted: 2024-02-15
• Study First Submitted QC: 2024-02-15
• Study First Posted: 2024-02-22
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-10
• Last Update Posted: 2025-03-11
• Primary Completion: 2025-05-31
• Study Completion: 2025-05-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

• 1. Patients diagnosed with autoimmune atrophic gastritis at the First Affiliated Hospital of Zhengzhou University, using the diagnostic criteria from the "Guidelines for the Diagnosis and Treatment of Chronic Gastritis in China (2022, Shanghai)" for the diagnosis of atrophic gastritis, combined with serum gastrin, PCA, or IFA for the diagnosis of autoimmune atrophic gastritis.

2. Patients who have signed the informed consent form for the clinical trial.

Exclusion Criteria

• 1. Patients with Betaine hydrochloride allergies. 2) Patients with gastric ulcers, gastroesophageal reflux disease, or cholelithiasis, as the administration of acid agents may worsen the condition or cause discomfort.

  2. Patients with gastrinomas or other conditions that can cause elevated gastrin levels, apart from autoimmune atrophic gastritis.

  3. Patients who are unable to provide informed consent or sign the informed consent form.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
serum gastrin levels	3 months	Comparison of the differences in serum gastrin levels between the post-trial and pre-trial measurements among the groups.

Secondary Outcome Measures

Name	Time	Method
the adverse reaction rates	3 months	Adverse reaction rate = Number of patients with adverse reactions in each group / Number of patients examined in each group.

Trial Locations

Locations (1)

First Affiliated Hospital of Zhengzhou University; 🇨🇳 Zhengzhou, Henan, China