L-cysteine Prevents Stomach Exposure to Carcinogenic Acetaldehyde

Study Overview
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Brief Summary
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Atrophic gastritis with hypochlorhydric milieu is a risk factor for gastric cancer. Microbes colonizing the acid-free stomach oxidize ethanol into acetaldehyde, a group 1 carcinogen. The aim is to assess gastric production of acetaldehyde and its inert condensation product, non-toxic 4-methyltiazolidine-2-carboxylic acid (MTCA), after alcohol intake under treatment with slow-release L-cysteine or placebo. Patients with biopsy-confirmed atrophic gastritis, low serum pepsinogen and high gastrin-17 are studied. On separate days, patients will be randomly assigned to receive 200 mg slow-release L-cysteine or placebo, then have intragastric instillation of 15% (0.3 g/kg) ethanol. After intake, gastric concentrations of acetaldehyde, ethanol, L-cysteine and MTCA are analysed for 4 hours. Expected results show mitigated exposure of the gastric mucosa to acetaldehyde.

Detailed Description
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Gastric infection with Helicobacter pylori induces chronic active gastritis which over the years develop atrophic gastritis with a hypochlorhydric milieu which is a risk factor for gastric cancer. Microbes colonizing acid-free stomach oxidize ethanol into acetaldehyde, considered a group 1 carcinogen. The aim of the study is to assess the gastric production of acetaldehyde and its inert condensation product, non-toxic 4-methyltiazolidine-2-carboxylic acid (MTCA), after alcohol intake under treatment with slow-release L-cysteine. Identical placebo tablets will be used for comparison. Patients with biopsy-confirmed atrophic gastritis, low serum pepsinogen and high gastrin-17 will be studied with case-control design. All subjects will be their own control. On separate days, patients are randomly assigned to receive 200 mg slow-release L-cysteine or placebo, then have intragastric instillation of 15% (0.3 g/kg) ethanol (corresponding to two glasses of wine). After intake, gastric sampling of fluid for a period of four hours is done and concentrations of acetaldehyde, ethanol, L-cysteine and MTCA are analysed. L-cysteine is expected to decrease gastric acetaldehyde concentrations and increase the MTCA level. Gastric L-cysteine and MTCA concentrations are expected to be maintained over the study period. With placebo, acetaldehyde is expected to be elevated along with ethanol concentrations. Based on these assumptions slow-release L-cysteine binds acetaldehyde to form inactive MTCA, which remains in gastric juice resulting in reduced local exposure of the gastric mucosa to carcinogenic acetaldehyde.

Official Title
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Slow-release L-cysteine Capsule Prevents Carcinogenic Gastric Acetaldehyde Exposure in Helicobacter-associated Atrophic Gastritis

Conditions
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Gastritis, Atrophic

Intervention / Treatment
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* Dietary Supplement: Slow-release L-cysteine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Helicobacter-associated chronic gastritis Hypochlorhydria Hypergastrinemia Hypopepsinogenemia Exclusion Criteria: Active peptic ulcer disease Other inflammatory gastrointestinal disease Gastrointestinal bleeding Gastrointestinal surgery Neurological disease Alcohol abuse Mental disorder Not able to sign informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Slow-release L-cysteine<br>Oral intake of slow-release L-cysteine 200 mg before challenge with ethanol. | Dietary Supplement: Slow-release L-cysteine<br>* Bind and inactivate acetaldehyde formed from ethanol by covalent binding to L-cysteine<br>* Other names: Acetium;|
| Placebo Comparator: Placebo<br>Oral intake of identically-looking placebo capsules | Dietary Supplement: Slow-release L-cysteine<br>* Bind and inactivate acetaldehyde formed from ethanol by covalent binding to L-cysteine<br>* Other names: Acetium;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acetaldehyde concentrations in the stomach | Binding of acetaldehyde to L-cysteine | 4 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 4-methyltiazolidine-2-carboxylic acid concentration in the stomach | Production of inert 4-methyltiazolidine-2-carboxylic acid after binding to L-cysteine | 4 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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atrohpic gastritis, acetaldehyde, ethanol, L-cysteine