Clinical trial NCT02524262: L-cysteine Prevents Stomach Exposure to Carcinogenic Acetaldehyde
Official title: Slow-release L-cysteine Capsule Prevents Carcinogenic Gastric Acetaldehyde Exposure in Helicobacter-associated Atrophic Gastritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gastritis, Atrophic
Keywords: atrohpic gastritis
acetaldehyde
ethanol
L-cysteine
Lead sponsor: Uppsala University
Sponsor class: OTHER
Collaborators: name: Biohit Oyj, Helsinki, Finland
name: University of Helsinki
name: Åbo Akademi University
name: CTC Clinical Trial Consultants AB
First posted: 2015-08-14
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Acetaldehyde concentrations in the stomach
timeFrame: 4 hours
Secondary outcomes:
measure: 4-methyltiazolidine-2-carboxylic acid concentration in the stomach
timeFrame: 4 hours
Other outcomes:
Locations:
city: Uppsala
country: Sweden
facility: Uppsala University
state: Uppsala county
Study officials:
affiliation: Uppsala University
name: Per M Hellstrom, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: