DyspepsiaPhase 4NCT00443963
Total Antioxidant Effects of Esomeprazole in Dyspeptic Patients Receiving Non-steroidal Anti-inflammatory Drugs
A Phase 4 study testing Esomeprazole Magnesium in people with Dyspepsia, run by Medstar Health Research Institute at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Dyspepsia
- What is being tested?
- Esomeprazole Magnesium
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2006to Dec 2006
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington Hospital Center
Washington D.C., District of Columbia, 20010
About this study
Official title: Effects of Esomeprazole Magnesium on Gastric Free Radical Production and Total Antioxidant Capacity in Dyspeptic Patients Receiving Non-steroidal Anti-inflammatory Drugs
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).
Read the 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.
- Conditions
- Dyspepsia
- Being tested
- Esomeprazole Magnesium
- Keywords
- Dyspepsia in patients taking NSAIDs
- Medical subject headings
- Dyspepsia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Esomeprazole MagnesiumDrug
Also called Ranitidine
PPI compared to H2RA
| Study group | Role | What they receive |
|---|---|---|
| PPI | Experimental | PPI Medication Receives: Drug: Esomeprazole Magnesium |
| H2RA | Experimental | H2RA Medication Receives: Drug: Esomeprazole Magnesium |
What is being measured
The primary outcome is the main question the study is designed to answer.
gastric levels of total antioxidant capacity and gastric lipid peroxide levels on Day 22
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).
Measured: 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2007 (estimated)
- Study startDec 2006 (estimated)
- Primary completionDec 2006
- Study completionDec 2006
Why it stopped: The study was not approved by the Human Studies Subcommittee.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for DyspepsiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medstar Health Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Principal investigator, Timothy Koch, Medstar Health Research Institute
- Investigators
- Timothy R Koch, MD, Principal investigator, Medstar Health Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00443963
- Sponsor's protocol ID
- IRUSESOM0391
- Status last verified
- Aug 2020
- First submitted
- 6 Mar 2007
- Last updated
- 24 Aug 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
Publications
Ofman JJ, Maclean CH, Straus WL, Morton SC, Berger ML, Roth EA, Shekelle PG. Meta-analysis of dyspepsia and nonsteroidal antiinflammatory drugs. Arthritis Rheum. 2003 Aug 15;49(4):508-18. doi: 10.1002/art.11192.
PubMed 12910557Hawkey C, Talley NJ, Yeomans ND, Jones R, Sung JJ, Langstrom G, Naesdal J, Scheiman JM; NASA1 SPACE1 Study Group. Improvements with esomeprazole in patients with upper gastrointestinal symptoms taking non-steroidal antiinflammatory drugs, including selective COX-2 inhibitors. Am J Gastroenterol. 2005 May;100(5):1028-36. doi: 10.1111/j.1572-0241.2005.41465.x.
PubMed 15842575Yeomans ND, Tulassay Z, Juhasz L, Racz I, Howard JM, van Rensburg CJ, Swannell AJ, Hawkey CJ. A comparison of omeprazole with ranitidine for ulcers associated with nonsteroidal antiinflammatory drugs. Acid Suppression Trial: Ranitidine versus Omeprazole for NSAID-associated Ulcer Treatment (ASTRONAUT) Study Group. N Engl J Med. 1998 Mar 12;338(11):719-26. doi: 10.1056/NEJM199803123381104.
PubMed 9494148Koch TR, Petro A, Darrabie M, Opara EC. Effect of the H, K-ATPase inhibitor, esomeprazole magnesium, on gut total antioxidant capacity in mice. J Nutr Biochem. 2004 Sep;15(9):522-6. doi: 10.1016/j.jnutbio.2004.03.003.
PubMed 15350983Koch TR, Petro A, Darrabie M, Opara EC. Effects of esomeprazole magnesium on nonsteroidal anti-inflammatory drug gastropathy. Dig Dis Sci. 2005 Jan;50(1):86-93. doi: 10.1007/s10620-005-1283-z.
PubMed 15712643
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Esomeprazole Magnesium on Gastric Free Radical Production and Total Antioxidant Capacity in Dyspeptic Patients Receiving Non-steroidal Anti-inflammatory Drugs
- ClinicalTrials.gov ID
- NCT00443963
- Acronym / sponsor ID
- IRUSESOM0391
- Conditions
- Dyspepsia
- Keywords
- Dyspepsia in patients taking NSAIDs
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: The study was not approved by the Human Studies Subcommittee.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Medstar Health Research InstituteUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- Dec 2006 (estimated)
- Primary completion
- Dec 2006 (actual)
- Study completion
- Dec 2006 (actual)
- First posted
- 7 Mar 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PPI | Experimental | Drug: Esomeprazole MagnesiumPPI Medication |
| H2RA | Experimental | Drug: Esomeprazole MagnesiumH2RA Medication |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (1 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Esomeprazole MagnesiumAlso: RanitidinePPI compared to H2RA | Drug | H2RA, PPI |
Primary outcome
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).
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2020.
- Background: PubMed 12910557Ofman JJ, Maclean CH, Straus WL, Morton SC, Berger ML, Roth EA, Shekelle PG. Meta-analysis of dyspepsia and nonsteroidal antiinflammatory drugs. Arthritis Rheum. 2003 Aug 15;49(4):508-18. doi: 10.1002/art.11192.
- Background: PubMed 15842575Hawkey C, Talley NJ, Yeomans ND, Jones R, Sung JJ, Langstrom G, Naesdal J, Scheiman JM; NASA1 SPACE1 Study Group. Improvements with esomeprazole in patients with upper gastrointestinal symptoms taking non-steroidal antiinflammatory drugs, including selective COX-2 inhibitors. Am J Gastroenterol. 2005 May;100(5):1028-36. doi: 10.1111/j.1572-0241.2005.41465.x.
- Background: PubMed 9494148Yeomans ND, Tulassay Z, Juhasz L, Racz I, Howard JM, van Rensburg CJ, Swannell AJ, Hawkey CJ. A comparison of omeprazole with ranitidine for ulcers associated with nonsteroidal antiinflammatory drugs. Acid Suppression Trial: Ranitidine versus Omeprazole for NSAID-associated Ulcer Treatment (ASTRONAUT) Study Group. N Engl J Med. 1998 Mar 12;338(11):719-26. doi: 10.1056/NEJM199803123381104.
- Background: PubMed 15350983Koch TR, Petro A, Darrabie M, Opara EC. Effect of the H, K-ATPase inhibitor, esomeprazole magnesium, on gut total antioxidant capacity in mice. J Nutr Biochem. 2004 Sep;15(9):522-6. doi: 10.1016/j.jnutbio.2004.03.003.
- Background: PubMed 15712643Koch TR, Petro A, Darrabie M, Opara EC. Effects of esomeprazole magnesium on nonsteroidal anti-inflammatory drug gastropathy. Dig Dis Sci. 2005 Jan;50(1):86-93. doi: 10.1007/s10620-005-1283-z.
- Related InfoLink provided by the sponsor.
Related trials for Dyspepsia
Active, not recruitingPhase 1
AutoSTEA for Adults With Functional Dyspepsia
Functional Dyspepsia
Recruiting
Probiotic and Ginger Supplement for Symptoms and Quality of Life in Functional Dyspepsia (SUBTILE)
Functional Dyspepsia
Enrolling by invitationObservational study
Body Surface Gastric Mapping to Evaluate Patients With Upper Gastrointestinal Symptoms and Controls
Motility Disorder, Gastroparesis
RecruitingPhase 4
Efficacy of Clostridium Butyricum in Alleviating Anxiety and Depression in Patients With Functional Dyspepsia
Functional Dyspepsia, Probiotics
RecruitingPhase 2
Exploring Novel Therapeutic Approaches for Disorders of Gut-Liver-Brain Interaction-H1/H2
Functional Gastrointestinal Disorders
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Timothy R Koch, MD principal investigator
Medstar Health Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Esomeprazole Magnesium in people with Dyspepsia, run by Medstar Health Research Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 24 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
gastric levels of total antioxidant capacity and gastric lipid peroxide levels on Day 22 (time frame: 1 week). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00443963, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2020.