Safety and Efficacy Study of Betaine Hydrochloride in Treating Hypergastrinemia in Patients With Autoimmune Gastritis

NCT06272500 | Recruiting

• 1 other identifier: 2024-KY-0146-001
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Autoimmune Gastritis

Outcome Measures

Primary Outcomes (1)

• The difference in serum gastrin (1 month)

  Comparison of the difference in serum gastrin before and after the trial within each group.

  1month

Secondary Outcomes (2)

• the adverse reaction rates

  3 months

• The difference in serum gastrin (3 month)

  3 months

Study Arms (2)

placebo group

PLACEBO COMPARATOR

receives oral administration of placebo, with two capsules before each meal.

Other: oral administration of receives only oral administration of placebo

Betaine HCl Group

EXPERIMENTAL

receives oral administration of Betaine hydrochloride（BHCL), with two capsules before each meal.

Dietary Supplement: oral administration of Betaine hydrochloride

Interventions

oral administration of receives only oral administration of placebo OTHER

receives oral administration of placebo, with two capsules before each meal.

placebo group

oral administration of Betaine hydrochloride DIETARY_SUPPLEMENT

receives oral administration of Betaine hydrochloride(BHCL), with two capsules before each meal.

Betaine HCl Group

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• \- 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.
• \) Patients who have signed the informed consent form for the clinical trial.

You may not qualify if:

• \) 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.
• \) Patients with gastrinomas or other conditions that can cause elevated gastrin levels, apart from autoimmune atrophic gastritis.
• \) Patients who are unable to provide informed consent or sign the informed consent form.

Sponsors & Collaborators

• Jianning Yao: lead

Study Sites (1)

First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, 436400, China

RECRUITING

Related Publications (15)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• Rustgi SD, Bijlani P, Shah SC. Autoimmune gastritis, with or without pernicious anemia: epidemiology, risk factors, and clinical management. Therap Adv Gastroenterol. 2021 Aug 31;14:17562848211038771. doi: 10.1177/17562848211038771. eCollection 2021.

  PMID: 34484423 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• Vannella L, Sbrozzi-Vanni A, Lahner E, Bordi C, Pilozzi E, Corleto VD, Osborn JF, Delle Fave G, Annibale B. Development of type I gastric carcinoid in patients with chronic atrophic gastritis. Aliment Pharmacol Ther. 2011 Jun;33(12):1361-9. doi: 10.1111/j.1365-2036.2011.04659.x. Epub 2011 Apr 15.

  PMID: 21492197 BACKGROUND

• Borch K, Ahren B, Ahlman H, Falkmer S, Granerus G, Grimelius L. Gastric carcinoids: biologic behavior and prognosis after differentiated treatment in relation to type. Ann Surg. 2005 Jul;242(1):64-73. doi: 10.1097/01.sla.0000167862.52309.7d.

  PMID: 15973103 BACKGROUND

• La Rosa S, Inzani F, Vanoli A, Klersy C, Dainese L, Rindi G, Capella C, Bordi C, Solcia E. Histologic characterization and improved prognostic evaluation of 209 gastric neuroendocrine neoplasms. Hum Pathol. 2011 Oct;42(10):1373-84. doi: 10.1016/j.humpath.2011.01.018. Epub 2011 May 4.

  PMID: 21531442 BACKGROUND

• Qvigstad G, Falkmer S, Westre B, Waldum HL. Clinical and histopathological tumour progression in ECL cell carcinoids ("ECLomas"). APMIS. 1999 Dec;107(12):1085-92. doi: 10.1111/j.1699-0463.1999.tb01513.x.

  PMID: 10660138 BACKGROUND

• Toh BH. Pathophysiology and laboratory diagnosis of pernicious anemia. Immunol Res. 2017 Feb;65(1):326-330. doi: 10.1007/s12026-016-8841-7.

  PMID: 27538411 BACKGROUND

• Grozinsky-Glasberg S, Alexandraki KI, Angelousi A, Chatzellis E, Sougioultzis S, Kaltsas G. Gastric Carcinoids. Endocrinol Metab Clin North Am. 2018 Sep;47(3):645-660. doi: 10.1016/j.ecl.2018.04.013. Epub 2018 Jul 11.

  PMID: 30098721 BACKGROUND

• Basuroy R, Srirajaskanthan R, Prachalias A, Quaglia A, Ramage JK. Review article: the investigation and management of gastric neuroendocrine tumours. Aliment Pharmacol Ther. 2014 May;39(10):1071-84. doi: 10.1111/apt.12698. Epub 2014 Mar 13.

  PMID: 24628514 BACKGROUND

Study Officials

• Jianning Yao, Dr.

  The First Affiliated Hospital of Zhengzhou University

  STUDY CHAIR

Central Study Contacts

Jianning Yao, Dr.

CONTACT

13733183434; rjyy@zzu.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Deputy Chief Physician

Study Record Dates

• First Submitted: February 15, 2024
• First Posted: February 22, 2024
• Study Start: February 1, 2024
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): May 31, 2026
• Last Updated: September 4, 2025

Record last verified: 2025-08

Locations

CN (1)