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

March 25, 2025 updated by: Second Affiliated Hospital, School of Medicine, Zhejiang University

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Autoimmune gastritis (AIG) is a chronic progressive autoimmune disorder characterized by the destruction of gastric parietal cells, leading to atrophy of the acid-secreting gastric mucosa. The loss of parietal cells results in gastric acid deficiency and intrinsic factor deficiency, which in turn impairs the absorption of iron and vitamin B12, leading to clinical manifestations such as iron deficiency anemia, pernicious anemia, and neuropsychiatric symptoms. Studies indicate that 4-12% of AIG patients develop type 1 gastric neuroendocrine tumors (NETs), and these patients also face a 3-7 times higher risk of gastric adenocarcinoma, with an incidence rate ranging from 0.9% to 9%.

Currently, there are no anti-inflammatory, immunosuppressive, or biologic therapies available for AIG. Standard treatment involves iron and vitamin B12 supplementation. Due to progressive parietal cell destruction, AIG patients exhibit a hypochlorhydric state, which reduces pepsin activity, impairs gastric motility, and may lead to small intestinal bacterial overgrowth (SIBO), often causing symptoms such as dyspepsia. Additionally, low gastric acid levels can interfere with the absorption of trace elements like iron and calcium. Insufficient gastric acid also promotes bacterial overgrowth in the stomach and increases N-nitroso compounds, elevating the risk of gastric cancer. Furthermore, gastric hypochlorhydria triggers a feedback mechanism that stimulates gastrin secretion from antral G cells, resulting in hypergastrinemia, which increases the risk of neuroendocrine tumors. Supplementation with betaine hydrochloride (with pepsin) can lower gastric pH in AIG patients, restore gastric acidity, improve protein digestion, alleviate dyspeptic symptoms, enhance the absorption of vitamins and minerals, correct gastric dysbiosis and SIBO, and reduce the risk of gastric cancer and neuroendocrine tumors.

This study aims to evaluate the effects of betaine hydrochloride (with pepsin) on gastrin levels, gastrointestinal symptoms, exhaled gas markers (NO, H2S, H2, and CH4), iron deficiency anemia parameters, AIG atrophy scores, and the incidence of gastric complications (hyperplastic polyps, neuroendocrine tumors, and gastric cancer). The study is divided into two groups: Group A (follow-up only, serving as the control group) and Group B (oral betaine hydrochloride). The study adopts a non-randomized, open-label, parallel-controlled design, where participants choose either the experimental group (oral betaine) or the control group (follow-up only) based on their preference. Both groups will be followed in parallel, and outcome differences will be compared, supplemented by within-group pre- and post-intervention analyses.

The study population consists of AIG patients diagnosed at the Second Affiliated Hospital of Zhejiang University School of Medicine. The diagnostic criteria for AIG are based on our team's published article in Clinics and Research in Hepatology and Gastroenterology: "A real-world study on the characteristics of autoimmune gastritis: A single-center retrospective cohort in China." Inclusion criteria include: serum gastrin levels >300 pmol/L or a history of type 1 gastric NETs or early gastric cancer treated with endoscopic submucosal dissection (ESD), age between 18 and 80 years, and signed informed consent. Exclusion criteria include: allergy to betaine hydrochloride, presence of peptic ulcers, other conditions causing elevated gastrin levels, and refusal to sign informed consent.

Group A (control group) will undergo follow-up only without intervention, while Group B will receive oral betaine hydrochloride (2 capsules three times daily with meals). The primary outcomes include changes in serum gastrin levels and improvements in the Gastrointestinal Symptom Rating Scale (GSRS). Secondary outcomes include changes in iron deficiency anemia markers (serum iron, ferritin, hemoglobin), exhaled gas markers (NO, H2S, H2, CH4), AIG atrophy scores, and the incidence of gastric complications (hyperplastic polyps, NETs, and gastric cancer).

Data will be collected through questionnaires, laboratory tests, endoscopy, and pathological records, with propensity score matching (PSM) used to adjust for baseline differences. The study has been approved by the Ethics Committee of the Second Affiliated Hospital of Zhejiang University School of Medicine. Adverse events will be monitored regularly, and serious adverse events will be reported promptly to the ethics committee and regulatory authorities.

This study will provide critical evidence on the efficacy and safety of betaine hydrochloride in treating AIG, exploring a simple, cost-effective therapeutic approach to alleviate symptoms and reduce the risk of severe complications.

Study Type

Interventional

Enrollment (Estimated)

100

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Jianshan Mao, MD, PhD
  • Phone Number: +86-571-8778-3540
  • Email: jshmao@zju.edu.cn

Study Locations

  • China
    • Zhejiang
      • Hangzhou City, Zhejiang, China, 310009
        • Recruiting
        • The Second Affiliated Hospital, Zhejiang University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. 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;
  2. 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);
  3. Age between 18 and 80 years;
  4. Patients who have signed the informed consent form for the clinical trial.

Exclusion Criteria:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Group A: Observation Only (Control Group)
Patients in this group will not receive any intervention and will only undergo regular follow-up and monitoring.
Other: No intervention (Control Group)
Patients in this group will receive standard care and undergo regular follow-up and monitoring without any additional treatment.
Experimental: Group B: Betaine Hydrochloride Supplementation
Patients in this group will receive oral betaine hydrochloride (with pepsin) .
Dietary supplement: Oral betaine hydrochloride (2 capsules, 3 times daily)
Oral betaine hydrochloride (with pepsin). Patients will take 2 capsules (648 mg per capsule) of betaine hydrochloride, 3 times daily with meals.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Serum Gastrin Levels
Time Frame: Baseline, 1 month, 3 months, 7 months, and 12 months.
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
Time Frame: Baseline, 1 month, 3 months, 7 months, and 12 months.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Exhaled Gas Markers (NO, H2S, H2, and CH4)
Time Frame: Baseline, 1 month, and 12 months.
Comparison of the differences in exhaled gas marker levels (NO, H2S, H2, and CH4) before and after the trial within and between groups.
Baseline, 1 month, and 12 months.
Iron Deficiency Anemia Indicators (Serum Iron, Ferritin, Hemoglobin)
Time Frame: Baseline, 1 month, and 12 months.
Comparison of the differences in iron deficiency anemia indicators (serum iron, ferritin, and hemoglobin) before and after the trial within and between groups.
Baseline, 1 month, and 12 months.
AIG Atrophy Score and Incidence of Gastric Complications
Time Frame: Baseline and 12 months.
Comparison of the differences in AIG atrophy scores and the incidence of gastric complications (hyperplastic polyps, neuroendocrine tumors, and gastric cancer) before and after the trial within and between groups.
Baseline and 12 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Second Affiliated Hospital, School of Medicine, Zhejiang University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 3, 2025

Primary Completion (Estimated)

June 30, 2026

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

March 12, 2025

First Submitted That Met QC Criteria

March 12, 2025

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)

March 30, 2025

Last Update Submitted That Met QC Criteria

March 25, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2024-0911

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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