TITLE: Eradication of Helicobacter pylori and Subsequent Effects on Peptic Ulcer Reoccurrence

DATE: May 9, 2014

PRINCIPLE INVESTIGATORS:
David Y. Graham Ginger M. Lew
123 Daisy Road, 3672 Apple Lane,
Fullerton, CA 92831 Fullerton, CA 92831
(657) 123-4567 (657) 365-8627
dgraham@fullerton.edu glew@fullerton.edu

Peter D. Klein Dolores G. Evans
75436 Daisy Road, 6426 Texas Street,
Fullerton, CA 92831 Fullerton, CA 92831
(657) 555-2625 (657) 625-2625
glew@fullerton.edu dgevans@fullerton.edu

Doyle J. Evans Zahid A. Saeed
764 Apple Lane, 557 Misty Drive,
Fullerton, CA 92831 Fullerton, CA 92831
(657) 124-6355 (657) 625-4665
djevans@fullerton.edu asaeed@fullerton.edu

Hoda M. Malaty Jennifer L. Spencer
769 New York Street, 456 Plant Lane,
Fullerton, CA 92831 Fullerton, CA 92831
(657) 276-7655 (657) 755-5757
hmalaty@fullerton.edu jspencer@fullerton.edu






ABSTRACT:
To study connections between treatment of Helicobacter pylori and ulcer reoccurrence,
two groups of patients who have received a single drug or triple drug treatment for gastric or
duodenal ulcers associated with H. pylori will be evaluated. The follow-up studies will take place
at one Veterans Affairs hospital to monitor patients and have access to patient records. It is
hypothesized that there will be a high correlation between full eradication of H. pylori infection
and decreased reoccurrence of gastric and duodenal ulcers. This follow-up study will employ
blinded experiments for the diagnosis of ulcers and detection of H. pylori bacteria utilizing
endoscopic techniques, enzyme-linked immunosorbent assays (ELISA), cell cultures and
histological analyses. Study outcomes could provide insight into the most effective drug
strategies for treatment and prevention of ulcers as well as significant contributions to the
scientific community, economic viability and national health.
Keywords: Helicobacter pylori, ulcers, reoccurrence, gastric, duodenal

PROJECT DESCRIPTION:
Objectives and Rationale: The objective of the proposed research is to fill a gap in
scientific knowledge by substantiating a causal connection between Helicobacter pylori bacterial
infections and the reoccurrence of both gastric and duodenal ulcers. Several studies have
shown that the H. pylori infection is a causal agent of gastritis (2-6). Additionally, H. pylori has
been authenticated as a strong predictor of peptic ulcer reoccurrence (2-6). However, adequate
studies addressing the reoccurrence of various types of peptic ulcers as a result of insufficient
eradication of H. pylori infections have not been performed. Previous studies have only shown a
connection between the eradication of H. pylori infection and general healing of gastritis. These
studies have confirmed the decrease in reoccurrence of duodenal ulcers in association with the
eradication of H. pylori, but have not been able to extend those findings to the reoccurrence of
other types of peptic ulcers. The incidence of duodenal ulcer reoccurrence has been
substantiated, but the connections between eradication of H. pylori and gastric ulcer
reoccurrence have not been satisfactorily studied (2-6, 11). By studying how various treatments
of H. pylori infection affect ulcers, this research aims to substantiate total H. pylori eradication as
a way to prevent long-term reoccurrence of duodenal and gastric ulcers and determine the best
treatment options. Targeting the overarching issue of total eradication of H. pylori and
reoccurrence of both duodenal and gastric ulcers would lead to significant contributions to the
body of knowledge. In addition to extending the scientific knowledge to include reoccurrence of
gastric ulcers, this research could further substantiate a role for H. pylori infection in the
reoccurrence of ulcers in general (11). As adequate controls and blinding groups were not used
in previous studies, more thorough studies into this connection are necessary and could be
reevaluated through this research (3, 5, 6). Additionally, several risk factors for peptic ulcer
reoccurrence have been authenticated, including male gender, alcohol use and smoking (1, 12).
This research approach could investigate associations between specific lifestyle choices and an
increase in peptic ulcer reoccurrence.
Significance and Broader Impacts: By studying how the eradication of H. pylori
infections affects the reoccurrence of gastric and duodenal ulcers, this research would be
significant across various realms including scientific, medicinal, humanitarian and economic.
From a medicinal standpoint, long-term implications of this research could aid in determining
which therapy types are best for total eradication of H. pylori infection, as well as the best
possible treatment for the specific degree of gastritis (1, 12). As ulcers can range in level from
mild to extremely severe, knowing how to best treat each incident could help prevent the
reoccurrence of ulcers on the front end of treatment. Furthermore, antibiotic resistant bacterial
infections are becoming more prevalent through public misuse and unnecessary prescription of
antibiotics (13). Understanding which treatments are necessary to treat various severities of H.
pylori and associated ulcers will aid in limiting the formation of strains of antibiotic resistant H.
pylori, as well as protect the efficacy of antibiotics for H. pylori infection treatment (13).
Additionally, investigating ulcer reoccurrence rates among patients in the general population
would be of great humanitarian significance. By decreasing the overall ulcer rates, reduction
would also lessen the incidence rate of patients with peptic ulcer reoccurrence. Reducing the
number of people struggling with reoccurring ulcers and receiving ongoing treatment will
increase patients quality of life in the future. Lastly, understanding the connection between H.
pylori and the reoccurrence of ulcers would be significant from an economic perspective. As the
people most prone to developing ulcers are of prime age to be a contributing member of the
workforce, determining which treatments of H. pylori lead to fewer reoccurrences of infection
and ulcers will result in a more healthy and vibrant national workforce. Additional benefits of a
wider knowledge base of drug therapies for peptic ulcers include vast economic benefits for
research and development, as well as distribution in the pharmaceutical industry.
Experimental Design: In order to substantiate the connection between H. pylori
eradication and duodenal and gastric ulcer reoccurrence, a long-term follow up study on
patients previously treated for peptic ulcers will be conducted (7). The study will take place at a
Veterans Affairs hospital and follow two groups of patients who had received different
treatments for either gastric or duodenal ulcers caused by H. pylori infections. The various
treatment groups include patients with gastric ulcers treated with either rantitidine alone or
rantitidine plus triple therapy and duodenal ulcers treated with either rantitidine alone or
rantitidine plus triple therapy. Triple therapy consists of treatment with bismuth subsalicylate,
tetracycline hydrochloride and metronidazole. Previously treated patients will be assessed for
symptoms of ulcer reoccurrence up to two years after their initial treatments. After treatments,
assessments will begin with one month increments and increase up to every three months for
the duration of the trials. Should symptoms return, patients will be monitored for the
reoccurrence of ulcers through endoscopies. Technicians will perform endoscopies in blinded
experiments to prevent the introduction of bias. Further assessment for H. pylori infection will be
done through the C-urea breath test, enzyme-linked immunosorbent assay (ELISA), bacterial
culture and histological analysis (8-10). Statistical analysis and predictive models of peptic ulcer
reoccurrence will be calculated using the lifetable method and assessed by chi-squared test or
Fisher exact test. Additionally, correlations between patient lifestyle and peptic ulcer
reoccurrence will be assessed in order to identify any overarching risk factors for H. pylori and
associated ulcers.
Conclusions and Future Work: Overall, the scope of medicinal, humanitarian and
economic benefits, as well as scientific knowledge that this research could provide is immense.
Significant impacts of this research include developing the best therapies for types and severity
of peptic ulcers and ultimately reducing the incidence of gastric and duodenal ulcer
reoccurrence. Additionally, developing simpler protocols and improved therapies for the
treatment of peptic ulcers and H. pylori infection would be beneficial for patients, clinicians and
industry alike. This research could also aid in future directions of research, such as determining
what the main risk factors are for H. pylori infections and peptic ulcer reoccurrence (6). Being
aware of the risk factors involved could help to ultimately implement better lifestyle choices for
both patients prone to H. pylori infection and ulcer reoccurrence as well as the general public.

REFERENCES CITED:
1. Sontag SJ. Current status of maintenance therapy in peptic ulcer disease. Am J
Gastroenterol. 1988;83:607-17.

2. Coghlan JG, Gilligan D, Humphries H, McKenna D, Dooley C, Sweeney E, et al.
Campylobacter pylori and recurrence of duodenal ulcersa 12-month follow-up study.
Lancet. 1987;2:1109-11.

3. Lambert JR, Borromeo M, Korman MG, Hansky J, Eaves ER. Effect of colloidal bismuth (De-
Nol) on healing and relapse of duodenal ulcers-role of Campylobacter pyloridis [Abstract].
Gastroenterology. 1987;92:1489.

4. Marshall BJ, Goodwin CS, Warren JR, Murray R, Blincow ED, Blackbourn SJ, et al.
Prospective double-blind trial of duodenal ulcer relapse after eradication of Campylobacter
pylori. Lancet. 1988;2:1437-42.

5. Rauws EA, Tytgat GN. Cure of duodenal ulcer associated with eradication of Helicobacter
pylori. Lancet. 1990;335:1233-5.

6. George LL, Borody TJ, Andrews P, Devine M, Moore-Jones D, Walton M, et al. Cure of
duodenal ulcer after eradication of Helicobacter pylori. Med J Aust. 1990;153:145-9.

7. Graham DY, Lew GM, Evans DG, Evans DJ Jr, Klein PD. Effect of triple therapy (antibiotics
plus bismuth) on duodenal ulcer healing with ranitidine. A randomized controlled trial. Ann
Intern Med. 1991;115:266-9.

8. Graham DY, Klein PD, Evans DJ Jr., Evans DG, Alpert LC, Opekun AR, et al. Campylobacter
pylori detected noninvasively by the 13C-urea breath test. Lancet. 1987;1:1174-7.

9. Klein PD, Graham DY. Campylobacter pylori detection by the 13C-urea breath test. In:
Campylobacter pylori and Gastroduodenal Disease. Rathbone BJ, Heatley V, eds.
Blackwell Scientific Publications, Oxford. 1989;94-106.

10. Evans DJ Jr, Evans DG, Graham DY, Klein PD. A sensitive and specific serologic test for
detection of Campylobacter pylori infection. Gastroenterology. 1989;96:1004-8.

11. Rauws EA, Langenberg W, Houthoff HJ, Zanen HC, Tytgat GN. Campylobacter pyloridis-
associated chronic active antral gastritis: a prospective study of its prevalence and the
effects of antibacterial and antiulcer treatment. Gastroenterology. 1988;94:33-40.

12. Van Deventer GM, Elashoff JD, Reedy TJ, Schneidman D, Walsh JH. A randomized study
of maintenance therapy with ranitidine to prevent the recurrence of duodenal ulcer. N Engl
J Med. 1989;320:1113-9.

13. Graham DY, Borsch GM. The who's and when's of therapy for Helicobacter pylori [Editorial].
Am J Gastroenterol. 1990;85:1552-5.

14. Graham DY, Lew GM, Malaty HM, Evans DG, Evans DJ Jr, Klein PD, et al. Factors
influencing the eradication of Helicobacter pylori with triple therapy. Gastroenterology.
1992;102:493-6.


BIOGRAPHICAL SKETCH:
My educational background is in biological science, specifically utilizing molecular and
microbiological techniques. My experience with biology has been developed through
coursework such as advances in molecular techniques, immunology, virology and microbiology.
Additionally, I have previous experience working with defense responses of tobacco plant
species and developing effective treatments against the Acinetobacter baumannii bacterial
infection. My intellectual and research interests include prevention and treatment strategies for
infectious diseases. Currently, I am a junior and will receive a Bachelors of Science degree in
Biological Sciences from California State University, Fullerton in May 2015.