Total Antioxidant Effects of Esomeprazole in Dyspeptic Patients Receiving Non-Steroidal Anti-Inflammatory Drugs

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00443963
Recruitment Status : Terminated (The Principal Investigator is no longer affiliated with the Study Site.)
First Posted : March 7, 2007
Last Update Posted : December 21, 2007
Information provided by:
Medstar Health Research Institute

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Dyspepsia Drug: Esomeprazole Magnesium Phase 4

Detailed Description:

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single
Primary Purpose: Treatment
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 Start Date : December 2006
Study Completion Date : December 2007

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Primary Outcome Measures :
  1. gastric levels of total antioxidant capacity and gastric lipid peroxide levels on Day 22

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00443963

United States, District of Columbia
Washington Hospital Center
110 Irving St. NW, Washington, District of Columbia, United States, 20010
Sponsors and Collaborators
Medstar Health Research Institute
Principal Investigator: Timothy R Koch, MD Washington Hospital Center

Additional Information:
Publications: Identifier: NCT00443963     History of Changes
Other Study ID Numbers: IRUSESOM0391
First Posted: March 7, 2007    Key Record Dates
Last Update Posted: December 21, 2007
Last Verified: December 2007

Keywords provided by Medstar Health Research Institute:
Dyspepsia in patients taking NSAIDs

Additional relevant MeSH terms:
Signs and Symptoms, Digestive
Signs and Symptoms
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Anti-Ulcer Agents
Gastrointestinal Agents
Proton Pump Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Antirheumatic Agents