Importance of Cytokines in Peptic Ulcer Disease: Implications for Treatment

NCT ID: NCT00534443

Last Updated: 2011-08-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-02-28
• Study Completion Date: 2009-09-30

Brief Summary

Although all PPIs are effective, there are some differences in their clinical performance, particularly in terms of the degree and speed of gastric acid suppression. Few data are also available about their effect of the pathophysiological mechanisms of gastritis and peptic ulcer disease. Aim of the present study is to investigate the effect of therapy with esomeprazole or rabeprazole on the mechanism of pathogenesis of gastritis and particularly on the pattern of release of pro- and anti- inflammatory cytokines associated to peptic ulcerative process by the gastric mucosa.

Detailed Description

Although all PPIs are effective, there are some differences in their clinical performance, particularly in terms of the degree and speed of gastric acid suppression. Few data are also available about their effect of the pathophysiological mechanisms of gastritis and peptic ulcer disease.

Triggering receptor expressed on myeloid cells (TREM)-1 is a recently discovered receptor expressed on the surface of neutrophils and monocytes. Engagement of TREM-1 has been reported to trigger the synthesis of proinflammatory cytokines. A soluble form of TREM-1, named sTREM-1, was observed and identified at significant levels in serum samples from patients with disease of the gastrointestinal tract inflammatory bowel disease. rendering interest about the implication of sTREM-1 in their pathogenesis.

sTREM-1 was also found elevated in the gastric juice of patients with peptic ulcer disease being correlated to the degree of the infiltration of the gastric mucosa by neutrophils.

Published data of our group elicit that sTREM-1 secretion is a crucial parameter for evolution from chronic gastritis to peptic ulcer disease. Samples of biopsies of gastric mucosa were cultured in the absence/presence of endotoxins showing that the inflamed mucosa was a potent secretor of sTREM-1 whatever ceased to exist post-antisecretory treatment.

Aim of the present study is to investigate the effect of therapy with esomeprazole or rabeprazole on the mechanism of pathogenesis of gastritis and particularly on the pattern of release of pro- and anti- inflammatory cytokines associated to peptic ulcerative process by the gastric mucosa.

Conditions

Peptic Ulcer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: SCREENING
• Blinding Strategy: NONE

Study Groups

1

A total of 130 patients with peptic ulcer disease and /or chronic gastritis will be enrolled in the study after written informed consent. Patients will be prescribed oral treatment with rabeprazole or esomeprazole according to standard guidelines. Rabeprazole is administered 20mg twice daily and esomeprazole 10 mg once daily. Selection of rabeprazole or esomeprazole is at the discretion of the attending physicians. The drug is administered for four weeks in patients with duodenal ulcers, for eight weeks in patients with gastric ulcers and for four weeks in patients with chronic gastritis.

Group Type: EXPERIMENTAL

Endoscopy of upper GI tract

Intervention Type: PROCEDURE

Upper GI endoscopy, one time on diagnosis and a second time 15 days after the end of the treatment. Gastric juice will be aspirated immediately after the entrance of the endoscope into the gastric lumen. Four biopsy specimens will be obtained from adjacent areas of the gastric antrum. Each biopsy will be used for in vitro culture. Blood will be sampled from one antecubital vein under aseptic conditions.

Each patient will be given antisecretory treatment and - if necessary- eradication treatment of H. pylori according to international guidelines.

Interventions

Endoscopy of upper GI tract

Upper GI endoscopy, one time on diagnosis and a second time 15 days after the end of the treatment. Gastric juice will be aspirated immediately after the entrance of the endoscope into the gastric lumen. Four biopsy specimens will be obtained from adjacent areas of the gastric antrum. Each biopsy will be used for in vitro culture. Blood will be sampled from one antecubital vein under aseptic conditions.

Each patient will be given antisecretory treatment and - if necessary- eradication treatment of H. pylori according to international guidelines.

Intervention Type: PROCEDURE

Other Intervention Names

Gastroscopy

Eligibility Criteria

Inclusion Criteria

• Written informed consent.
• Abdominal pain or discomfort and/or
• Epigastric pain with nausea and vomiting and/or
• Dyspepsia.

Exclusion Criteria

• Recent upper GI bleeding
• Gastric carcinoma
• Diabetes mellitus
• Liver cirrhosis
• Acute or chronic renal failure
• The ingestion of any antimicrobial or antisecretory medication for at least 15 days prior to endoscopy.

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

Sponsors

University of Athens

OTHER

Sponsor Role: lead

Responsible Party

University of Athens, Medical School, Greece

Principal Investigators

Evangelos J. Giamarellos-Bourboulis, MD, PhD

Role: STUDY_CHAIR

4th Department of Internal Medicine, ATTIKON University Hospital, 124 62 Athens, Greece

Vassileios Koussoulas, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Endoscopy, Sismanoglion General Hospital, 151 26 Athens, Greece

Locations

Department of Endoscopy, Sismanoglion General Hospital

Athens, , Greece

Countries

Greece

References

Tzivras M, Koussoulas V, Giamarellos-Bourboulis EJ, Tzivras D, Tsaganos T, Koutoukas P, Giamarellou H, Archimandritis A. Role of soluble triggering receptor expressed on myeloid cells in inflammatory bowel disease. World J Gastroenterol. 2006 Jun 7;12(21):3416-9. doi: 10.3748/wjg.v12.i21.3416.

Reference Type: BACKGROUND

PMID: 16733861 (View on PubMed)

Koussoulas V, Vassiliou S, Demonakou M, Tassias G, Giamarellos-Bourboulis EJ, Mouktaroudi M, Giamarellou H, Barbatzas C. Soluble triggering receptor expressed on myeloid cells (sTREM-1): a new mediator involved in the pathogenesis of peptic ulcer disease. Eur J Gastroenterol Hepatol. 2006 Apr;18(4):375-9. doi: 10.1097/00042737-200604000-00010.

Reference Type: BACKGROUND

PMID: 16538108 (View on PubMed)

Koussoulas V, Giamarellos-Bourboulis EJ, Barbatzas C, Pimentel M. Serum sTREM-1 as a surrogate marker of treatment outcome in patients with peptic ulcer disease. Dig Dis Sci. 2011 Dec;56(12):3590-5. doi: 10.1007/s10620-011-1761-4. Epub 2011 Jun 2.

Reference Type: DERIVED

PMID: 21633832 (View on PubMed)

Other Identifiers

3530

Identifier Type: -

Identifier Source: org_study_id