L-cysteine Prevents Stomach Exposure to Carcinogenic Acetaldehyde

• Sponsor: Per Hellström (Other)
• Overall Status: Completed
• CT.gov ID: NCT02524262
• Collaborator: Biohit Oyj, Helsinki, Finland (Other), University of Helsinki (Other), Åbo Akademi University (Other), CTC Clinical Trial Consultants AB (Industry)
• Enrollment: 8
• Location: 1
• Arms: 2
• Duration (Months): 33
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Gastritis, Atrophic	Dietary Supplement: Slow-release L-cysteine	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Participant)
• Primary Purpose: Prevention
• Official Title: Slow-release L-cysteine Capsule Prevents Carcinogenic Gastric Acetaldehyde Exposure in Helicobacter-associated Atrophic Gastritis
• Study Start Date: Dec 1, 2012
• Actual Primary Completion Date: Sep 1, 2015
• Actual Study Completion Date: Sep 1, 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Acetaldehyde concentrations in the stomach [4 hours]

   Binding of acetaldehyde to L-cysteine

Secondary Outcome Measures

1. 4-methyltiazolidine-2-carboxylic acid concentration in the stomach [4 hours]

   Production of inert 4-methyltiazolidine-2-carboxylic acid after binding to L-cysteine

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Uppsala University	Uppsala	Uppsala county	Sweden	75185

Sponsors and Collaborators

• Per Hellström
• Biohit Oyj, Helsinki, Finland
• University of Helsinki
• Åbo Akademi University
• CTC Clinical Trial Consultants AB

Investigators

• Principal Investigator: Per M Hellstrom, MD, PhD, Uppsala University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Per Hellström, Professor, Uppsala University
• ClinicalTrials.gov Identifier: NCT02524262
• Other Study ID Numbers: 620070-SWE-2012
• First Posted: Aug 14, 2015
• Last Update Posted: Jan 25, 2016
• Last Verified: Jan 1, 2016

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Per Hellström, Professor, Uppsala University: atrohpic gastritis; acetaldehyde; ethanol; L-cysteine
• Additional relevant MeSH terms: Gastritis; Gastritis, Atrophic; Atrophy

Study Results

No Results Posted as of Jan 25, 2016