The Effects of Aspirin and Acetaminophen on the Stomach in Healthy Volunteers
The Effects of Aspirin and Acetaminophen on the Stomach in Healthy Volunteers
Aspirin is a medication commonly used to relieve minor pains. Aspirin has also been used to
 prevent heart attacks and strokes. Aspirin, however, can also cause damage to the stomach
 and/or intestinal lining leading to the development of erosions ("small sores") and/or ulcers
 ("large sores"). Erosions may cause bleeding ("bleeding ulcers") and/or perforations ("holes
 in the stomach"). Acetaminophen, often referred by the brand name, Tylenol, is also used to
 treat minor pains but is not commonly recognized to cause damage to the stomach lining.

 Many patients often take both of these medications together. While the effects on the stomach
 lining of each medication, when used alone, are known, the effects of both medications, when
 used together, are not.

 The purpose of this study is to show whether or not the collective effects of both aspirin
 and acetaminophen, when used together, increase the damage on the stomach lining when
 compared to either medication alone.
Low dose aspirin is used for the primary and secondary prevention of cardiovascular
 thromboembolic events. As a non-selective inhibitor of cyclooxygenase, aspirin use results in
 irreversible COX-1 inhibition leading to impaired platelet aggregation. However, aspirin also
 inhibits COX-1 activity in the gastric mucosa by suppressing the synthesis of protective
 prostaglandins. In doing so, this creates a state of propensity for the development of
 aspirin-associated gastrointestinal ulcers and ulcer complications.

 A high proportion of aspirin users also require concomitant use of anti-inflammatory
 medications for the treatment of pain and arthritis. However, evidence suggests that the risk
 of developing gastroduodenal ulcers and ulcer complications is significantly increased when
 aspirin is co-administered with other nonselective NSAIDs. In a previous study, concomitant
 aspirin (325 mg daily) in healthy subjects taking naproxen (500mg bid) was associated with
 endoscopic ulcer rates of 27.3% as compared to aspirin alone (7.6%). In a separate and
 independent trial of similar design, patients using 81 mg of aspirin in conjunction with
 daily naproxen also resulted in a higher incidence of gastric and duodenal ulcers than
 aspirin therapy alone. Beyond endoscopic ulcer rates, the risk of upper gastrointestinal
 hemorrhage has been reported to be substantially increased with concurrent administration of
 low-dose aspirin with nonselective NSAIDS. These data suggest that the gastrointestinal
 toxicity of combined aspirin with other NSAIDs may be more than additive.
Inclusion Criteria:

 1. Be a cooperative, healthy male or female between the ages of 18-75 inclusive.

 2. Have a physical examination which reveals no clinically significant abnormalities at
 the screening visit.

 3. Have fewer than 6 gastric or duodenal erosions visible on nasal endoscopy at Visit 2.

 4. If the subject is female and of childbearing potential, she has been using effective
 contraception since the last date of her menses, will continue to use effective
 contraception during the study period, is not breast-feeding or lactating at screening
 and has had a negative urine pregnancy test at screening. Women who have been
 post-menopausal for less than 2 years will also require a urine pregnancy test at
 screening.

 5. Have provided written informed consent prior for admission to this study.

 6. H. pylori negative serologic exam prior to baseline nasal EGD.

 Exclusion Criteria:

 1. Active GI disease (e.g. IBD), or a history of GI ulcers or bleeding

 2. History of gastric or intestinal surgery

 3. Use of ASA, NSAIDs, coxibs, or acetaminophen at any dose within 2 weeks prior to the
 randomization visit of the study.

 4. Positive FOBT at baseline.

 5. Use of over-the-counter or prescription: sucralfate, antacids, H2-receptor
 antagonists, misoprostol, or proton pump inhibitors 4 weeks prior to enrollment and/or
 during the study

 6. A known allergy to the topical anesthetic, lidocaine.