Safety and Efficacy Study of Betaine Hydrochloride in Treating Hypergastrinemia in Patients With Autoimmune Gastritis
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In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: oral administration of receives only oral administration of placebo, oral administration of Betaine hydrochloride.
- Who it may be relevant to
- Registry conditions: Autoimmune Gastritis. Basic parameters: No limits · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- China
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
Safety and Efficacy Study of Betaine Hydrochloride in Treating Hypergastrinemia in Patients With Autoimmune Gastritis.
Overview
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.
Interventions
- Other oral administration of receives only oral administration of placebo
receives oral administration of placebo, with two capsules before each meal. - Dietary supplement oral administration of Betaine hydrochloride
receives oral administration of Betaine hydrochloride(BHCL), with two capsules before each meal.
Primary outcome measures
- The difference in serum gastrin (1 month) [Time frame: 1month]
Secondary outcome measures (2)
- the adverse reaction rates [Time frame: 3 months]
- The difference in serum gastrin (3 month) [Time frame: 3 months]
Eligibility criteria
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.
3\) Patients with gastrinomas or other conditions that can cause elevated gastrin levels, apart from autoimmune atrophic gastritis.
4\) Patients who are unable to provide informed consent or sign the informed consent form.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Double blind
- Primary purpose
- Treatment
Study locations
China · 1 center
- First Affiliated Hospital of Zhengzhou University — Zhengzhou
Publications
- Toh BH, Chan J, Kyaw T, Alderuccio F. Cutting edge issues in autoimmune gastritis. Clin Rev Allergy Immunol. 2012 Jun;42(3):269-78. doi: 10.1007/s12016-010-8218-y. PMID 21174235
- Anagnostopoulos GK, Ragunath K, Shonde A, Hawkey CJ, Yao K. Diagnosis of autoimmune gastritis by high resolution magnification endoscopy. World J Gastroenterol. 2006 Jul 28;12(28):4586-7. doi: 10.3748/wjg.v12.i28.4586. PMID 16874879
- Martinelli TM, van Driel IR, Alderuccio F, Gleeson PA, Toh BH. Analysis of mononuclear cell infiltrate and cytokine production in murine autoimmune gastritis. Gastroenterology. 1996 Jun;110(6):1791-802. doi: 10.1053/gast.1996.v110.pm8964405. PMID 8964405
- Rustgi SD, Bijlani P, Shah SC. Autoimmune gastritis, with or without pernicious anemia: epidemiology, risk factors, and clinical management. Ther Adv Gastroenterol. 2021 Aug 31;14:17562848211038771. doi: 10.1177/17562848211038771. eCollection 2021. PMID 34484423
- Minalyan A, Benhammou JN, Artashesyan A, Lewis MS, Pisegna JR. Autoimmune atrophic gastritis: current perspectives. Clin Exp Gastroenterol. 2017 Feb 7;10:19-27. doi: 10.2147/CEG.S109123. eCollection 2017. PMID 28223833
- Lenti MV, Rugge M, Lahner E, Miceli E, Toh BH, Genta RM, De Block C, Hershko C, Di Sabatino A. Autoimmune gastritis. Nat Rev Dis Primers. 2020 Jul 9;6(1):56. doi: 10.1038/s41572-020-0187-8. PMID 32647173
- Niederle MB, Hackl M, Kaserer K, Niederle B. Gastroenteropancreatic neuroendocrine tumours: the current incidence and staging based on the WHO and European Neuroendocrine Tumour Society classification: an analysis based on prospectively collected parameters. Endocr Relat Cancer. 2010 Oct 5;17(4):909-18. doi: 10.1677/ERC-10-0152. Print 2010 Dec. PMID 20702725
- Delle Fave G, O'Toole D, Sundin A, Taal B, Ferolla P, Ramage JK, Ferone D, Ito T, Weber W, Zheng-Pei Z, De Herder WW, Pascher A, Ruszniewski P; Vienna Consensus Conference participants. ENETS Consensus Guidelines Update for Gastroduodenal Neuroendocrine Neoplasms. Neuroendocrinology. 2016;103(2):119-24. doi: 10.1159/000443168. Epub 2016 Jan 19. No abstract available. PMID 26784901
Identifiers
NCT: NCT06272500 · 2024-KY-0146-001