L-cysteine Prevents Stomach Exposure to Carcinogenic Acetaldehyde

Gastritis, Atrophic Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02524262
• Other study ID #: 620070-SWE-2012
• Status: Completed
• Phase: Phase 2
• First received: August 13, 2015
• Last updated: January 21, 2016
• Start date: December 2012
• Est. completion date: September 2015

Study information

• Verified date: January 2016
• Source: Uppsala University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Sweden: Regional Ethical Review BoardSweden: Medical Products Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: September 2015
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Single Blind (Subject), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Atrophy
• Gastritis
• Gastritis, Atrophic

Intervention

Dietary Supplement:
• Slow-release L-cysteine
Bind and inactivate acetaldehyde formed from ethanol by covalent binding to L-cysteine

Locations

Country	Name	City	State
Sweden	Uppsala University	Uppsala	Uppsala county

Sponsors (5)

Lead Sponsor	Collaborator
Per Hellström	Åbo Akademi University, Biohit Oyj, Helsinki, Finland, Clinical Trial Consultants, Uppsala, Sweden, Helsinki University

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Acetaldehyde concentrations in the stomach	Binding of acetaldehyde to L-cysteine	4 hours	No
Secondary	4-methyltiazolidine-2-carboxylic acid concentration in the stomach	Production of inert 4-methyltiazolidine-2-carboxylic acid after binding to L-cysteine	4 hours	No