Total Antioxidant Effects of Esomeprazole in Dyspeptic Patients Receiving Non-Steroidal Anti-Inflammatory Drugs
Information source: Medstar Research Institute
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Dyspepsia
Intervention: Esomeprazole Magnesium (Drug)
Phase: Phase 4
Sponsored by: Medstar Research Institute
Official(s) and/or principal investigator(s):
Timothy R Koch, MD, Principal Investigator, Affiliation: Washington Hospital Center
We hypothesize that patients receiving NSAID drugs with dyspeptic symptoms have increased
production of gastric levels of free radicals. The primary objective of the study is to
determine if Esomeprazole Magnesium increases gastric total antioxidant capacity and
decreases gastric free radical production in humans. Patients (age 18 years and older) with
no history of upper GI bleeding who are receiving non-steroidal anti-inflammatory drugs and
then develop dyspepsia will be recruited from our primary care clinic in Washington, DC. All
eligible individuals will undergo biopsies of antrum and corpus. The subjects will be
randomized to receive either Zantac OTC or Nexium for 15 days. On day 15, all patients will
undergo repeat upper endoscopy to obtain biopsies of antrum and corpus. Tissue samples will
then be extracted to determine total antioxidant capacity and lipid peroxide levels (as an
indirect marker of free radical production).
Official title: Effects of Esomeprazole Magnesium on Gastric Free Radical Production and Total Antioxidant Capacity in Dyspeptic Patients Receiving Non-Steroidal Anti-Inflammatory Drugs
Study design: Treatment, Randomized, Single Blind, Active Control, Parallel Assignment, Efficacy Study
Primary outcome: gastric levels of total antioxidant capacity and gastric lipid peroxide levels on Day 22
An extensive meta-analysis has confirmed that dyspeptic symptoms are common in individuals
using non-steroidal anti-inflammatory drugs (NSAIDs) (1). Both esomeprazole 20 mg daily and
esomeprazole 40 mg daily have been shown to be more effective than placebo for the control of
upper gastrointestinal symptoms in patients receiving NSAIDs (2).
The mechanisms by which H, K-ATPase inhibitors protect against NSAID gastropathy remain
unclear, although it is known that their use is more clinically effective than the use of the
H2-receptor antagonist, ranitidine (3).
The biochemical basis for NSAID gastropathy is not fully understood (6). One potential
mechanism for the development of gastric damage in individuals receiving NSAIDs is oxidative
stress related to depletion of gastric antioxidants. A recent endoscopic study in patients
supports the hypothesis that NSAID use associated with gastric bleeding decreases gastric
mucosal glutathione levels (7), a major cellular micronutrient antioxidant produced by
mammalian cells. We have been working on the possibility that activation of afferent nerve
fibers by oxidative stress can induce abdominal discomfort during the use of NSAIDs. This
notion is supported by animal studies that have shown that oxidants evoke neurotransmitter
release from enteric neurons (8). This experimental result suggests that abnormal tissue
levels of oxygen-derived free radicals (oxidative stress) could directly activate afferent
enteric nerves or could alter gastric motility via a neuronal mechanism.
The hypothesis of this present proposal is that patients receiving NSAID drugs with dyspeptic
symptoms have increased production of gastric levels of free radicals. The primary aims of
this study are to examine gastric free radical production and total antioxidant capacity in
patients who are taking NSAID drugs and have dyspeptic symptoms. Gastric free radical
production and total antioxidant capacity will be measured before and after receiving either
15 days of daily esomeprazole magnesium or ranitidine.
Minimum age: 18 Years.
Maximum age: N/A.
- Patients who are capable of providing informed consent, ages 18 years old and older.
Patients will be eligible who are taking non-steroidal anti-inflammatory drugs on a
daily basis and present with at least a 1 week history of dyspeptic symptoms including
epigastric or upper abdominal discomfort or pain.
- Patients presenting with only a complaint of heartburn will be excluded. Patients
with alarm symptoms of vomiting, evidence of bleeding, inadvertent weight loss, or
dysphagia will be excluded. Patients will be excluded if they have had upper
endoscopy within 6 months prior to randomization. At the initial visit all
individuals will have a Helicobacter pylori IgG serology drawn; all individuals with a
positive serology will be excluded. This study will not enroll patients with a
previous history of myocardial infarction, cerebrovascular infarction, gastric or
duodenal ulcer disease, or carcinoma. The study will not enroll patients who have
received a H, K-ATPase inhibitor within the past 2 weeks. At the initial upper
endoscopy, all patients with esophageal ulcer, esophageal cancer, gastric ulcer,
gastric cancer, and duodenal ulcer will be excluded.
Locations and Contacts
Washington Hospital Center, 110 Irving St. NW, Washington, District of Columbia 20010, United States
Ofman JJ, Maclean CH, Straus WL, Morton SC, Berger ML, Roth EA, Shekelle PG. Meta-analysis of dyspepsia and nonsteroidal antiinflammatory drugs. Arthritis Rheum. 2003 Aug 15;49(4):508-18. Review.
Hawkey C, Talley NJ, Yeomans ND, Jones R, Sung JJ, Langstrom G, Naesdal J, Scheiman JM; NASA1 SPACE1 Study Group. Improvements with esomeprazole in patients with upper gastrointestinal symptoms taking non-steroidal antiinflammatory drugs, including selective COX-2 inhibitors. Am J Gastroenterol. 2005 May;100(5):1028-36.
Yeomans ND, Tulassay Z, Juhasz L, Racz I, Howard JM, van Rensburg CJ, Swannell AJ, Hawkey CJ. A comparison of omeprazole with ranitidine for ulcers associated with nonsteroidal antiinflammatory drugs. Acid Suppression Trial: Ranitidine versus Omeprazole for NSAID-associated Ulcer Treatment (ASTRONAUT) Study Group. N Engl J Med. 1998 Mar 12;338(11):719-26.
Koch TR, Petro A, Darrabie M, Opara EC. Effect of the H, K-ATPase inhibitor, esomeprazole magnesium, on gut total antioxidant capacity in mice. J Nutr Biochem. 2004 Sep;15(9):522-6.
Koch TR, Petro A, Darrabie M, Opara EC. Effects of esomeprazole magnesium on nonsteroidal anti-inflammatory drug gastropathy. Dig Dis Sci. 2005 Jan;50(1):86-93.
Starting date: December 2006
Ending date: December 2007
Last updated: December 17, 2007