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

This study has been terminated.
(The Principal Investigator is no longer affiliated with the Study Site.)
Sponsor:
ClinicalTrials.gov Identifier:
NCT00443963
First Posted: March 7, 2007
Last Update Posted: December 21, 2007
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.
Collaborator:
AstraZeneca
Information provided by:
Medstar Health Research Institute
  Purpose
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 Intervention Phase
Dyspepsia Drug: Esomeprazole Magnesium Phase 4

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by Medstar Health Research Institute:

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

Estimated Enrollment: 20
Study Start Date: December 2006
Study Completion Date: December 2007
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.

  Eligibility

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
Criteria

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.
  Contacts and Locations
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 ClinicalTrials.gov identifier (NCT number): NCT00443963


Locations
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
AstraZeneca
Investigators
Principal Investigator: Timothy R Koch, MD Washington Hospital Center
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00443963     History of Changes
Other Study ID Numbers: IRUSESOM0391
First Submitted: March 6, 2007
First Posted: March 7, 2007
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:
Dyspepsia
Signs and Symptoms, Digestive
Signs and Symptoms
Esomeprazole
Anti-Inflammatory Agents
Antioxidants
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
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Antirheumatic Agents