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

of Helicobacter pylori

Sean A. Page

March 08
th
, 1987

1337 Wunderkind lane

(111) 867-5309

seanpage007@yahoo.com
Abstract

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 deficit, and the exploration of simpler and less
evasive treatments should be warranted.

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. 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). The significant
reduction in the quality of life 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).
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. 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 by an 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 expect
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 a proposed and supported treatment strategy.
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 type
of 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 possibly; with supporting evidence showing a supported direction of
research continuing 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 the its application in a
real world context.

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 pathology of disease. My
ability to conduct high-level research has been 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.
Understanding key traits of the immune system through my research on the
potential of exercise in attenuating the depression induced deregulation of pro- and
anti-inflammatory cytokine production, allow a heighted 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.


References

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