Exploratory Study on the Efficacy of Betaine Hydrochloride in Treating Autoimmune Gastritis

NCT06881511 | Recruiting DMC

• 1 other identifier: 2024-0911
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Autoimmune gastritis (AIG) is a chronic autoimmune disorder characterized by parietal cell destruction and oxyntic mucosal atrophy, leading to achlorhydria and intrinsic factor deficiency. These pathological changes impair iron and vitamin B12 absorption, resulting in iron-deficiency anemia, pernicious anemia, and neuropsychiatric manifestations. Notably, 4-12% of AIG patients develop type 1 gastric neuroendocrine tumors, while facing a 3-7 fold increased risk of gastric adenocarcinoma with an incidence of 0.9-9%. Current management of AIG is limited to iron and vitamin B12 replacement, as no disease-modifying therapies exist. The progressive hypochlorhydria reduces pepsin activity, impairs gastric motility, and promotes small intestinal bacterial overgrowth (SIBO), causing dyspeptic symptoms and micronutrient malabsorption. Furthermore, gastric hypoacidity increases N-nitroso compound formation and triggers hypergastrinemia, elevating risks for both gastric cancer and neuroendocrine tumors. This clinical trial investigates whether betaine hydrochloride (with pepsin) supplementation can restore gastric acidity and improve clinical outcomes in AIG. We will evaluate its effects on gastrin levels, gastrointestinal symptoms, exhaled gas markers (NO, H₂S, H₂, CH₄), anemia parameters, endoscopic atrophy scores, and incidence of gastric complications (hyperplastic polyps, neuroendocrine tumors, and adenocarcinoma). The study aims to provide evidence for a potential therapeutic strategy addressing both symptoms and long-term complications of AIG.

Conditions

Autoimmune Gastritis

Keywords

Autoimmune Gastritis; Iron-Deficiency Anemia; Stomach Neoplasms; Neuroendocrine Tumors; Betaine; Hydrochloride; Pepsin; Gastrointestinal Agents; Gastrins

Outcome Measures

Primary Outcomes (2)

• Serum Gastrin Levels

  Comparison of the differences in serum gastrin levels before and after the trial within and between groups.

  Baseline, 1 month, 3 months, 7 months, and 12 months.

• Gastrointestinal Symptom Scores

  Gastrointestinal symptom scores will be assessed using the Gastrointestinal Symptom Rating Scale (GSRS) . Comparison of the differences in gastrointestinal symptom scores before and after the trial within and between groups.

  Baseline, 1 month, 3 months, 7 months, and 12 months.

Secondary Outcomes (3)

• Exhaled Gas Markers (NO, H2S, H2, and CH4)

  Baseline, 1 month, and 12 months.

• Iron Deficiency Anemia Indicators (Serum Iron, Ferritin, Hemoglobin)

  Baseline, 1 month, and 12 months.

• AIG Atrophy Score and Incidence of Gastric Complications

  Baseline and 12 months.

Study Arms (2)

Group A: Observation Only (Control Group)

OTHER

Patients in this group will not receive any intervention and will only undergo regular follow-up and monitoring.

Other: No intervention (Control Group)

Group B: Betaine Hydrochloride Supplementation

EXPERIMENTAL

Patients in this group will receive oral betaine hydrochloride (with pepsin) .

Dietary Supplement: Oral betaine hydrochloride (2 capsules, 3 times daily)

Interventions

No intervention (Control Group) OTHER

Patients in this group will receive standard care and undergo regular follow-up and monitoring without any additional treatment.

Group A: Observation Only (Control Group)

Oral betaine hydrochloride (2 capsules, 3 times daily) DIETARY_SUPPLEMENT

Oral betaine hydrochloride (with pepsin). Patients will take 2 capsules (648 mg per capsule) of betaine hydrochloride, 3 times daily with meals.

Group B: Betaine Hydrochloride Supplementation

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients diagnosed with autoimmune gastritis at the Second Affiliated Hospital of Zhejiang University School of Medicine, with the diagnostic criteria for autoimmune gastritis based on the article "A real-world study on the characteristics of autoimmune gastritis: A single-center retrospective cohort in China" published by our team in the journal Clinics and Research in Hepatology and Gastroenterology;
• Gastrin levels greater than 300 pmol/L or a history of type 1 gastric neuroendocrine tumors or early gastric cancer treated with endoscopic submucosal dissection (ESD);
• Age between 18 and 80 years;
• Patients who have signed the informed consent form for the clinical trial.

You may not qualify if:

• Patients allergic to betaine hydrochloride;
• Patients with peptic ulcers;
• Patients with any condition other than autoimmune gastritis that causes elevated gastrin levels (e.g., gastrinoma);
• Patients who refuse to sign the informed consent form.

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead

Study Sites (1)

The Second Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310009, China

RECRUITING

Related Publications (10)

• Song M, Camargo MC, Katki HA, Weinstein SJ, Mannisto S, Albanes D, Surcel HM, Rabkin CS. Association of Antiparietal Cell and Anti-Intrinsic Factor Antibodies With Risk of Gastric Cancer. JAMA Oncol. 2022 Feb 1;8(2):268-274. doi: 10.1001/jamaoncol.2021.5395.

  PMID: 34913949 BACKGROUND

• Rossi RE, Elvevi A, Sciola V, Mandarino FV, Danese S, Invernizzi P, Massironi S. Paradoxical association between dyspepsia and autoimmune chronic atrophic gastritis: Insights into mechanisms, pathophysiology, and treatment options. World J Gastroenterol. 2023 Jun 21;29(23):3733-3747. doi: 10.3748/wjg.v29.i23.3733.

  PMID: 37398891 BACKGROUND

• Singh S, Chakole S, Agrawal S, Shetty N, Prasad R, Lohakare T, Wanjari M, Yelne S. A Comprehensive Review of Upper Gastrointestinal Symptom Management in Autoimmune Gastritis: Current Insights and Future Directions. Cureus. 2023 Aug 13;15(8):e43418. doi: 10.7759/cureus.43418. eCollection 2023 Aug.

  PMID: 37706145 BACKGROUND

• Osmola M, Chapelle N, Vibet MA, Bigot-Corbel E, Masson D, Hemont C, Jirka A, Blin J, Tougeron D, Moussata D, Lamarque D, Josien R, Mosnier JF, Martin J, Matysiak-Budnik T. Iron and Vitamin B12 Deficiency in Patients with Autoimmune Gastritis and Helicobacter pylori Gastritis: Results from a Prospective Multicenter Study. Dig Dis. 2024;42(2):145-153. doi: 10.1159/000535206. Epub 2024 Jan 10.

  PMID: 38198775 BACKGROUND

• Jove A, Lin C, Hwang JH, Balasubramanian V, Fernandez-Becker NQ, Huang RJ. Serum Gastrin Levels Are Associated With Prevalent Neuroendocrine Tumors in Autoimmune Metaplastic Atrophic Gastritis. Am J Gastroenterol. 2025 May 1;120(5):1140-1143. doi: 10.14309/ajg.0000000000003235. Epub 2024 Nov 26.

  PMID: 39588964 BACKGROUND

• Chen C, Yang Y, Li P, Hu H. Incidence of Gastric Neoplasms Arising from Autoimmune Metaplastic Atrophic Gastritis: A Systematic Review and Case Reports. J Clin Med. 2023 Jan 30;12(3):1062. doi: 10.3390/jcm12031062.

  PMID: 36769710 BACKGROUND

• Gomez Cifuentes JD, Sparkman J, Graham DY. Management of upper gastrointestinal symptoms in patients with autoimmune gastritis. Curr Opin Gastroenterol. 2022 Nov 1;38(6):600-606. doi: 10.1097/MOG.0000000000000878. Epub 2022 Sep 9.

  PMID: 36165039 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

• Taylor L, McCaddon A, Wolffenbuttel BHR. Creating a Framework for Treating Autoimmune Gastritis-The Case for Replacing Lost Acid. Nutrients. 2024 Feb 27;16(5):662. doi: 10.3390/nu16050662.

  PMID: 38474790 BACKGROUND

• Chen Y, Ji X, Zhao W, Lin J, Xie S, Xu J, Mao J. A real-world study on the characteristics of autoimmune gastritis: A single-center retrospective cohort in China. Clin Res Hepatol Gastroenterol. 2025 Apr;49(4):102556. doi: 10.1016/j.clinre.2025.102556. Epub 2025 Feb 15.

  PMID: 39961485 BACKGROUND

MeSH Terms

Conditions

Anemia, Iron-Deficiency; Stomach Neoplasms; Neuroendocrine Tumors

Interventions

Control Groups; Betaine

Condition Hierarchy (Ancestors)

Anemia, Hypochromic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Iron Deficiencies; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods; Trimethyl Ammonium Compounds; Quaternary Ammonium Compounds; Amines; Organic Chemicals; Onium Compounds

Central Study Contacts

Jianshan Mao, MD, PhD

CONTACT

+86-571-8778-3540; jshmao@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study will employ a linear mixed-effects model to analyze changes in primary outcomes (GSRS scores and serum gastrin levels), with the intervention effect evaluated through group-by-time interactions. For secondary outcomes, continuous variables will be analyzed using multiple linear regression, while categorical variables will be analyzed using logistic regression or Cox proportional hazards models. All models will adjust for baseline differences (via propensity score matching) and potential confounders. Model assumptions will be validated through residual analysis and diagnostic plots. Sensitivity analyses will include per-protocol vs intention-to-treat comparisons and alternative propensity score methods. Data analysis will be performed using R (version 4.0) or SAS (version 9.4).

Study Record Dates

• First Submitted: March 12, 2025
• First Posted: March 18, 2025
• Study Start: January 3, 2025
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 30, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)