L-cysteine Prevents Stomach Exposure to Carcinogenic Acetaldehyde

NCT ID: NCT02524262

Last Updated: 2016-01-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-12-31
• Study Completion Date: 2015-09-30

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.

Conditions

Gastritis, Atrophic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

Slow-release L-cysteine

Oral intake of slow-release L-cysteine 200 mg before challenge with ethanol.

Group Type: EXPERIMENTAL

Slow-release L-cysteine

Intervention Type: DIETARY_SUPPLEMENT

Bind and inactivate acetaldehyde formed from ethanol by covalent binding to L-cysteine

Placebo

Oral intake of identically-looking placebo capsules

Group Type: PLACEBO_COMPARATOR

Slow-release L-cysteine

Intervention Type: DIETARY_SUPPLEMENT

Bind and inactivate acetaldehyde formed from ethanol by covalent binding to L-cysteine

Interventions

Slow-release L-cysteine

Bind and inactivate acetaldehyde formed from ethanol by covalent binding to L-cysteine

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

Acetium

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Biohit Oyj, Helsinki, Finland

UNKNOWN

Sponsor Role: collaborator

University of Helsinki

OTHER

Sponsor Role: collaborator

Åbo Akademi University

OTHER

Sponsor Role: collaborator

CTC Clinical Trial Consultants AB

INDUSTRY

Sponsor Role: collaborator

Per Hellström

OTHER

Sponsor Role: lead

Responsible Party

Per Hellström

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Per M Hellstrom, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Uppsala University

Locations

Uppsala University

Uppsala, Uppsala County, Sweden

Countries

Sweden

Other Identifiers

620070-SWE-2012

Identifier Type: -

Identifier Source: org_study_id