Total Antioxidant Effects of Esomeprazole 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 Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind
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|
- gastric levels of total antioxidant capacity and gastric lipid peroxide levels on Day 22
|Study Start Date:||December 2006|
|Study Completion Date:||December 2007|
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.
|United States, District of Columbia|
|Washington Hospital Center|
|110 Irving St. NW, Washington, District of Columbia, United States, 20010|
|Principal Investigator:||Timothy R Koch, MD||Washington Hospital Center|