Clinical trial NCT00534443: Importance of Cytokines in Peptic Ulcer Disease: Implications for Treatment
Official title: A Clinical Study of the Efficacy of Esomeprazole or Rabeprazole on the Pattern of Release of Pro- and Anti-inflammatory Cytokines From Gastric Mucosa of Patients With Peptic Ulcer Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Peptic Ulcer
Keywords: peptic ulcer
gastritis
sTREM-1
cytokines
Changes of inflammatory status in gastric mucosa
sTREM-1 as a disease marker
Lead sponsor: University of Athens
Sponsor class: OTHER
First posted: 2007-09-24
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: SCREENING

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.

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.

Primary outcomes:
measure: Effect of treatment on changes of cytokines levels in serum of patients
timeFrame: Baseline and 8 weeks
Secondary outcomes:
measure: Effect of treatment on changes of cytokines levels in supernatants of cultures of gastric mucosa
timeFrame: Baseline and 8 weeks
Other outcomes:
Locations:
city: Athens
country: Greece
facility: Department of Endoscopy, Sismanoglion General Hospital
Study officials:
affiliation: 4th Department of Internal Medicine, ATTIKON University Hospital, 124 62 Athens, Greece
name: Evangelos J. Giamarellos-Bourboulis, MD, PhD
role: STUDY_CHAIR
affiliation: Department of Endoscopy, Sismanoglion General Hospital, 151 26 Athens, Greece
name: Vassileios Koussoulas, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.