Official Title: “Effects of Esomeprazole Magnesium on Gastric Free Radical Production and Total Antioxidant Capacity in Dyspeptic Patients Receiving Non-Steroidal Anti-Inflammatory Drugs”

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).

Study Type: Interventional

Study Design: Treatment, Randomized, Single Blind, Active Control, Parallel Assignment, Efficacy Study

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.

Intervention(s) in this Clinical Trial

• Drug: Esomeprazole Magnesium

Primary Measures

• gastric levels of total antioxidant capacity and gastric lipid peroxide levels on Day 22

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Medstar Research Institute

Overall Clinical Trial Officials and Contacts

Timothy R Koch, MD Principal Investigator Washington Hospital Center  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00443963

Study ID Number: IRUSESOM0391

ClinicalTrials.gov Identifier: NCT00443963

Health Authority: United States: Food and Drug Administration