L-cysteine Prevents Stomach Exposure to Carcinogenic Acetaldehyde

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

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.

Study Overview

• Status: Completed
• Conditions: Gastritis, Atrophic
• Intervention / Treatment: Dietary supplement: Slow-release L-cysteine

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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2

Contacts and Locations

Study Locations

• Sweden
  • Uppsala county
    • Uppsala, Uppsala county, Sweden, 75185
      • Uppsala University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Per Hellström
• Collaborators: University of Helsinki; CTC Clinical Trial Consultants AB; Biohit Oyj, Helsinki, Finland; Åbo Akademi University
• Investigators: Principal Investigator: Per M Hellström, MD, PhD, Uppsala University

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: August 13, 2015
• First Submitted That Met QC Criteria: August 13, 2015
• First Posted (Estimate): August 14, 2015

Study Record Updates

• Last Update Posted (Estimate): January 25, 2016
• Last Update Submitted That Met QC Criteria: January 21, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: ethanol; atrohpic gastritis; acetaldehyde; L-cysteine
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Gastroenteritis; Pathological Conditions, Anatomical; Gastritis; Atrophy; Gastritis, Atrophic
• Other Study ID Numbers: 620070-SWE-2012

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: World J Gastroenterol