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Novel Therapy for Long-term Recurrence of Gastric or Duodenal Ulcers: Treatment of Helicobacter


A Research Proposal Submitted to
The Nation Science Foundation


Sean A. Page

Sean A. Page
Department of Psychology
(111) 867-5309
1337 Wunderkind Lane
Hollywood, CA 92832

NSF Grant proposal, 1987


A lifetime of recurrent ulcers is characteristic of Peptic ulcer disease. Treatments for this disease
can attenuate present ulcers but does not affect the natural history of the disease. Recent studies have
suggested a novel theory, that Helicobacter pylori (H. pylori) may play a role in the pathogenesis of this
disease. To explore this claim controlled experimentation with patients showing ulcers will be
administered via two randomly assigned treatments, either ranitidine alone or triple therapy. Triple
therapy is a novel treatment including two antimicrobial agents, tetracycline hydrochloride (500mg four
times, daily) and metronidazole (250 three times, daily) as well as bismuth (151mg per tablet)
subsalicylate. Results comparing these treatments may confirm the findings of previous research, that
patients in whom H. pylori infection was eradicated remained asymptomatic and ulcer free. However this
huge burst of antibiotics itself is a potential danger and the exploration of simpler treatments with less risk
are warranted.

1. Project Description:

Our projects objective for the proposed period of the study, 1988-1990, is to explore the
effectiveness of a novel therapy in treating H. pylori associated gastric and duodenal ulcers, as well as its
role in recurrence. Presently the pathology of these ulcers is not well understood, especially in the context
of the potential of microbial interactions that may induce recurrent flare-ups. Recent studies have
suggested the eradication of H. pylori may have a critical role in the natural history of duodenal ulcer (2-
6). Conventional antiulcer treatments have been shown to only ameliorate the expression of these ulcers
during treatment and rapidly recur when ceased (1,2). A significant reduction in the quality of the lives of
patients with gastric and duodenal ulcers warrants a necessity to identify effective treatment strategies to
benefit this population. Previous research on the topic does not utilize reliable methodology, having no
control groups for relative comparison nor any form of blinding, making it necessary to explore the role
H. pylori and potential treatments in the context of valid methodological design (3, 4, 5).
1.1 Methodology
1.2 Participants
Patients, who show healed gastric and duodenal ulcers, from previous treatments, will be
recruited to participate in our follow-up study (7). The proposed design for this study consists of a simple
dichotomous protocol by randomly assigned administration of either ranitidine (300g once daily in the
evening) or the novel triple therapy (bismuth subsalicylate, 151mg once daily, tetracycline hydrochloride,
500mg four times a day, and metronidazole, 250mg thrice a day). Bismuth subsalicylate will be
administered for the initial two weeks when beginning therapy. The sample of participants that are of
preliminary interested are Veterans, staying in the Veteran Medical Center. After this period, these
participants will be entered into our proposed follow-up study, consisting 16 weeks of treatment. To
acquire the expected significance that we believe will occur, we ideal would need to have around a 75%
retention of subjects from the first stage of the study, requiring about 110 participants. Patients will be
followed-up after 1 month, 3 months and recur every 3 months for 2 years. We will documents the use of
antiulcer treatments (including antacids); those receiving non-steroidal drugs will be able to continue if
they wish. Patients who original had been assigned to the ranitidine treatment will be able to cross-over
to the new therapy and will be termed cross-overs.
1.3 Procedures
We will identify ulcers by the use valid and reliable methodological protocols and procedures that
have been previously utilized in similar studies (10, 11, 14). The method of endoscopy will be used to
visual explore and record breaks in the epithelial lumen of gastric and duodenal tracts. Ulcers for this
study are operationalized as a circumscribed break in the duodenal mucosa, at least 5mm in diameter,
show apparent depth and should be covered with exudate. Patients will be tested for the presence of for H.
pylori every three months and when symptomatic. This will be assessed by the C-urea breath test (8,9), by
a sensitive enzyme-linked immunosorbent assay (ELISA) specific to IgG antibody to assess cell-
associated proteins of H. pylori (10), cultures, and by histologic evaluation of antral mucosal biopsies.
Eradication of H. pylori is will be defined as no evidence of this bacterium for one or more months after
discontinuing the treatment. It is expected that the probability of recurrence for the patients who receive
the triple therapy and ranitidine will show significantly less recurrence than those who received ranitidine
alone. It is also expected that those who received the triple therapy exclusively will also show a
significant reduction in the recurrence of gastric and duodenal ulcers. It is unclear whether there will be a
difference in the effectiveness of either treatment based on the type of ulcer. However we believe that
duodenal ulcers will be more challenging in the context of all treatments. This study may ultimately
benefit our understanding of the role of H. pylori eradication in the treatment of these ulcers and
document the results of the proposed and supported treatment strategy.
1.3 Concluding Statements
To ensure the ethical conducts of scientific research this experimental design, the Institutional
Review Board at Veteran Affairs Medical Center will assess its relevance, validity, and practicality, and
begin when passed. Overall the primary goal of the results of this study is to explore the benefit of
eradication of H. pylori in attenuating of gastric and duodenal ulcers over long-term periods. With recent
research documenting the role of H. pylori in the pathogenesis of these ulcers warrants a need to identify
effective and practical treatments through the conduct of research, such as this, designed for biomedical
applications. Conducting this research is an important and necessary practice to cultivate increased
awareness and understanding of pathways that play a role in the pathogenesis of these ulcers, the
improved well being of individual and the resulting societal benefits of their increase quality of life is the
drive of our research. In addition the toll that recurrent disease takes on the economic resource of the
United States is a deficit that should be avoided if possible. Supporting evidence continues to show a
supported direction of research to search for better treatments is justified in the mentioned
multidimensional benefits of creating a reliable treatment for gastric and duodenal ulcers. The last
important goal of this research that has not been mentioned is the support, progressive, and competitive
advance of STEM literacy and competency in the United States. The network between STEM research,
the industry required for the production of required materials and the federal, as well as private health
care systems will overall increase the efficiency of research and its application in the real world context.

2. Biographical Sketch:

I am currently a double major in Psychology and Comparative Religion at California State
University, Fullerton. I have had experience and demonstrated proficiency in several biologically relevant
methods such as PCR (polymerase-chain reaction), RT-PCR (reverse transcription-PCR), sub-cloning, gel
electrophoresis, and enzyme-linked immunosorbent assays. Participation in courses such as, laboratory
techniques in biopsychology, intermediate cellular biology, and neuroscience give a solid foundation of
biological interactions and their role in pathologies of a disease. My ability to conduct high-level research
is demonstrated from my participation in the Minority Access to Research Careers (MARC) program.
Having experience in bio-medically related research, I have a sturdy understanding of the proper
scientific conduct necessary to produce valid, reliable and most importantly ethical research. Key traits of
the immune system have been introduced and mastered through my research on the potential of exercise
in attenuating the depression induced deregulation of pro- and anti-inflammatory cytokine production.
This understanding allows a heightened sense of awareness in regard to the molecular pathways that may
play a role in the pathology of gastric and duodenal ulcers, as well as pathways for their treatment.


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