Gastritis, Atrophic
Conditions
Keywords
atrohpic gastritis, acetaldehyde, ethanol, L-cysteine
Brief summary
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
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.
Interventions
DIETARY_SUPPLEMENTSlow-release L-cysteine
Bind and inactivate acetaldehyde formed from ethanol by covalent binding to L-cysteine
Sponsors
Biohit Oyj, Helsinki, Finland
University of Helsinki
Åbo Akademi University
CTC Clinical Trial Consultants AB
Per Hellström
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Acetaldehyde concentrations in the stomach | 4 hours | Binding of acetaldehyde to L-cysteine |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 4-methyltiazolidine-2-carboxylic acid concentration in the stomach | 4 hours | Production of inert 4-methyltiazolidine-2-carboxylic acid after binding to L-cysteine |
Countries
Sweden
Outcome results
None listed