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Total Antioxidant Effects of Esomeprazole in Dyspeptic Patients Receiving Non-steroidal Anti-inflammatory Drugs

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ClinicalTrials.gov Identifier: NCT00443963
Recruitment Status : Withdrawn (The study was not approved by the Human Studies Subcommittee.)
First Posted : March 7, 2007
Last Update Posted : August 24, 2020
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Timothy Koch, Medstar Health Research Institute

Tracking Information
First Submitted Date  ICMJE March 6, 2007
First Posted Date  ICMJE March 7, 2007
Last Update Posted Date August 24, 2020
Estimated Study Start Date  ICMJE December 2006
Actual Primary Completion Date December 2006   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 19, 2020)
gastric levels of total antioxidant capacity and gastric lipid peroxide levels on Day 22 [ Time Frame: 1 week ]
Measurement of tissue levels in stomach biopsies of total antioxidant capacity (in nmole of Trolox equivalent/g wet tissue) and lipid peroxides (in nmole/g wet tissue).
Original Primary Outcome Measures  ICMJE
 (submitted: March 6, 2007)
gastric levels of total antioxidant capacity and gastric lipid peroxide levels on Day 22
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Total Antioxidant Effects of Esomeprazole in Dyspeptic Patients Receiving Non-steroidal Anti-inflammatory Drugs
Official Title  ICMJE Effects of Esomeprazole Magnesium on Gastric Free Radical Production and Total Antioxidant Capacity in Dyspeptic Patients Receiving Non-steroidal Anti-inflammatory Drugs
Brief Summary The principal investigator hypothesizes that participants 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. Participants (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 participants will undergo biopsies of antrum and corpus. The participants will be randomized to receive either Zantac OTC or Nexium for 15 days. On day 15, all participants 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).
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. The principal investigator has 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 participants 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 participants 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  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Investigator)
Primary Purpose: Treatment
Condition  ICMJE Dyspepsia
Intervention  ICMJE Drug: Esomeprazole Magnesium
PPI compared to H2RA
Other Name: Ranitidine
Study Arms  ICMJE
  • Experimental: PPI
    PPI Medication
    Intervention: Drug: Esomeprazole Magnesium
  • Experimental: H2RA
    H2RA Medication
    Intervention: Drug: Esomeprazole Magnesium
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: August 19, 2020)
0
Original Enrollment  ICMJE
 (submitted: March 6, 2007)
20
Actual Study Completion Date  ICMJE December 2006
Actual Primary Completion Date December 2006   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Participants who are capable of providing informed consent, ages 18 years old and older. Partipants who are taking non-steroidal anti-inflammatory drugs on a daily basis must present with at least a 1 week history of dyspeptic symptoms including epigastric or upper abdominal discomfort or pain.

Exclusion Criteria:

  • Participants presenting with only a complaint of heartburn will be excluded. Participants with alarm symptoms of vomiting, evidence of bleeding, inadvertent weight loss, or dysphagia will be excluded. Participants will be excluded if they have had upper endoscopy within 6 months prior to randomization. At the initial visit, participants will have a Helicobacter pylori IgG serology drawn and all participants with a positive serology will be excluded. Participants with a previous history of myocardial infarction, cerebrovascular infarction, gastric or duodenal ulcer disease, or carcinoma will be excluded. The study will not enroll participants who have received a H, K-ATPase inhibitor within the past 2 weeks. At the initial upper endoscopy, all participants with esophageal ulcer, esophageal cancer, gastric ulcer, gastric cancer, and duodenal ulcer will be excluded.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00443963
Other Study ID Numbers  ICMJE IRUSESOM0391
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Timothy Koch, Medstar Health Research Institute
Study Sponsor  ICMJE Medstar Health Research Institute
Collaborators  ICMJE AstraZeneca
Investigators  ICMJE
Principal Investigator: Timothy R Koch, MD Medstar Health Research Institute
PRS Account Medstar Health Research Institute
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP