Eradicating Helicobacter pylori infection may prove to cure symptoms of patients with

uninvestigated dyspepsia.
Nicholas Armada, Alyssa Bormann, Stacy Guzman, Lien Phan
9 March 2015
800 N State College Blvd, Fullerton, CA 92831
(657) 278-2011
FullertonScience@fullerton.edu

Abstract
ManyA large number of primary care patients with dyspepsia, a common upper abdomen clinical
problem, remains uninvestigated and suffer from univestigateduninvestigated dyspepsia and often
requires urgent symptom relief from symptoms (Jones, R., 2002).1 Further analysis of Helicobacter pylori
(H pylori), a bacterium that may cause contribute to dyspepsia, would reduce any alarming symptoms and
provide individualized treatment for H. pylori-infected patients patients. .
Goals and objectives/rationale
Using a test for H pylori and eradicate strategy to combat uninvestigated dyspepsia
Very brief methods
A HHelisal Rrapid blood test and a 13C -urea breath test are used aswill be used to for initial
screening test to exclude patients negative for H pylorisince we only want to screen patients that are
positive for H. pylori. Randomization of eExperimental and placebo groups will be randomized tested and
treated forprior to H pylori treatment. and dDyspepsia symptoms will be relieved using using omeprazole.
H pylori will be eradicated with as dyspepsia symptom relief drug and metronidazole and clarithromycin
antibiotics. as antibiotics for H pylori. We hypothesize that the eradication of H. pylori will result in the
improvement or cure of primary care patients with dyspepsia in patients with uninvestigated dyspepsia in
primary care. Exploring the relationship and impact thatbetween H. pylori contributes tando dyspepsia
will allow us to develop more efficient and effective methods for detecting and treating dyspepsia
symptoms at minimal costs. If family practitioners and gastrointestinal specialists are able to A test and
eradicate strategy to eliminate the symptoms of functional dyspepsia will ease physical discomfort and
avoid unnecessary prescription drugs for patients.utilize a test and eradicate strategy for eliminating the
symptoms of patients with functional dyspepsia, the over-prescription of proton-pump inhibitor (PPI)
drugs can be avoided and the physical discomfort that the patients experience can be addressed quicker.

Searchable Keywords: Uninvestigated dyspepsia, H. pylori, 13C-urea breath test, Helisal blood test, PPI.
Introduction
Indigestion, also known as dyspepsia,Dyspepsia, commonly known as indigestion, still remains a
major healthcare concern. Widely common in primary care patients, tThe high prevalence of dyspepsia
continues to negatively impact the lives of more than a third of the general population, most of which are
patients in primary care.care (Tougas, Chen, Hwang, Liu, & Eggleston, 1999).2 Such patients are prone to
structural diseases such as: ulcer cancer, malignancy, and peptic ulcer disease. (Chiba 1989, Veldhuyzen
van Zanten SJ, Flook N, Chiba N, Armstrong D, Barkun A, Bradette M, et al, 2000). 3 There is some
evidence that demonstrates the bacterium Helicobacter pylori (H pylori) as the leading cause of
dyspepsia, however, its association remains unclear due to its inadequate definition (Suzuki, H. ,
Nishizawa, T. , & Hibi, T., 2011).4 Although controversy coincides with the definition of dyspepsia and its
relationship with H. pylori, in this experiment, any of the following upper gastrointestinal tract symptoms
will be considered, including: heartburn, excessive burning, abdominal bloating, nausea, regurgitation,
slow digestion, or satiety (Chiba, N., Van Zanten, S. J., Sinclair, P., Ferguson, R. A., Escobedo, S., &
Grace, E., 2002).5 Patients experience pPrevailing symptoms such as heartburn and regurgitation are
likely diagnosed gastroesophagealgastro esophageal reflux disease (GERD), thus patients experiencing
such symptomsand will be excluded from this study.
Uninvestigated dyspepsia is the designated term for patients with new or recurrent dyspeptic
symptoms, in whom no investigations have been previously undertaken (Jones, R., 2002).1 Patients with
dyspepsia are normally referred to a specialist and consider undergo a visual examination known as
endoscopy. This nonsurgical procedure has its limitations to accurately evaluate dyspepsia and H. pylori.,
Ffurthermore, endoscopy is accompanied with high healthcare costs and is linked with dangerous bacteria
that can infect patients (Anderson, M. , Gan, S. , Fanelli, R. , Baron, T. , Banerjee, S. , et al., 2008).6
ThusSince dyspepsia is so prevalent and is associated with high healthcare costs, it is important find the
most accurate techniqueefficient method to detect this bacterium in dyspepticthe source of dyspepsia in

patients whose major symptom is gastritis primary care patients and completely destroy the presence of
the bacterium H. pylori with gastritis (Shah, 2007).7
Objectives/Rationale
The causes for symptoms of dyspepsia are relatively unknown and are rarely investigated.
Dyspepsia is difficult to investigate because the diagnosis is often made by a subjective, verbal reporting
of symptoms by the patient. Physicians whose patients come in with complaints of dyspepsia often
prescribe their patients with drugs, such as over-prescription of proton-pump inhibitor (PPI) drugs
proton-pump inhibitors (PPIs) that will only mask the symptoms and have not shown to be substantially
effective in combating the source compared to placebo with a 1.81 odds ratio (Shiau et al, 2002).8 After
attempting 2.5 courses of drug treatment, Ffamily practitioners usually move to further investigating the
causes further after attempting 2.5 courses of drug treatment (Chiba et al, 1998).9 However,
investigations remain ambiguous and the diagnosis put forward is usually functional dyspepsia (Talley
et al, 1998).10
A recommendation stating that a test and treat strategy may create significant symptom relief in
patients with uninvestigated dyspepsia has been made but it has not been evaluated in randomized and
controlled clinical trials (Hunt et al, 1999).11 Our laboratory plans to use a 13-C -urea breath test to screen
for patients that test positive for H. pylori infection. We plan to treat them with omeprazole (a PPI),
metronidazole (an antibiotic), and clarithromycin (an antibiotic). We also plan to use placebos of the
antibiotic medications as a control. What our study will add to what is known today is that physicians
might be able to reduce symptoms in patients with uninvestigated dyspepsia by eradicating H. pylori with
antibiotics in patients who test positive for the bacterial infection as opposed to just prescribing PPI drugs.
Methods

In order to evaluate the role of H pylori role in functional dyspepsia, we will treat patients with
genuine and placebo antibiotics in a double blind studyFunctional dyspepsia patients are usually have H
pylori infection. But it is unsure that the symptoms can be cause by H pylori in the lack of peptic

ulceration. . This is the reason why we will treat patients with a double blind placebo to determine
whether or not H pylori is a origin of functional dyspepsia, as expected decreasing in symptoms when H
pylori was eradicated. Patients Patients will be selected to participate in the study if they are at least 18
years or older and have experienceds the uninvestigated dyspepdyspepticsia symptoms for at least 3
months prior to the study. To avoid ambiguity, we define dyspepsia as a symptom complex of epigastric
pain that originates in the upper gastrointestinal tract .1212. are qualified if they are 18 years old or older
with unvestigated symptoms of dyspepsia within 3 months. We will assume that the success rate is 39%
for eradication and 20% for placebo basing on the estimated differec. From this assumption, 150 patients
each sides (including 120 evaluable patients) are needed to accomplish two tailed significance level of
0.05.
The patientsy will be treated randomly twice a day daily for seven7 days, using the PPI
omeprazole 20mg for dyspepsiaas symptom ms relief drug, as well as antibiotics , metronidazole 500mg,
and clarithromycin 250mg as antibiotics or omeprazole 20mg, placebo metronidazole, and placebo
clarithromycin. for H. pylori eradication. A control group will be set up to take omeprazole 20mg along
with placebo forms of both antibiotics. It is also very important to validate the accuracy of the tests for
diagnosing the H pylori infection to determine whether the test for Helicobacter pylori and its treatment
enhance the symptoms in uninvestigated dyspepsia patients or not. We will use a rapid blood test and 13
13C- urea breath test to validate the patients positive test results for H. pylori infection in our study.
Previous rResearch hases showned that rapid blood test and 13C- urea breath tests have very high
sensitivitiesy (88% and 93.5%, respectively accordingly) and specificitiesy (91% and 97.3% accordingly,
respectively) to detect H pylori infection.*** The high percent of sensitivity and specificity of these
methods is not the only reason why we choose them. Some may rise the question for using serological
testing. We have chosen the rapid blood test and 13C-urea breath tests over serological testing
becauseEven though serological testing is widely used to detect H pylori but it require specific laboratory,
which leads to delay. requires specialty laboratory equipment. Sending out Having to send samples out to
another lab for testing will greatly delay the study. The rapid blood test is more expensive than serology

kits, Tthe outcome results of the rapid blood test are available obtainable in ten10 minutes. This quick
result time makes the test convenient for primary care facilities to use, giving the convenient and accuracy
in primary care. The And Helikit for 13C- urea breath test will be used for initial screening for H. pylori
infection. The test is easy to use and is noninvasive in that patients only need to take a pill and provide a
breath samplebring excellent clinical sensitivity and the potential for repeat, multiple, noninvasive
evaluation of H pylori status. It offers a simple and easy approach to diagnosis of H pylori infection.
So we will use this test as an initial screening test to exclude patients with negative for H pylori. 13
Uninvestigated patientsPatients diagnosed with uninvestigated dyspepsia for for at least 3 months
or more, who have both positive results for for these two testsboth tests then will be treated withwill be
enrolled in computer randomization. This technique will eliminate any biased evaluation toComputer
randomization will be used to allocate patients twice for daily for seven days. We will follow up with
these se patients monthly in for up to a year 12 months and record progress based basing on clinical ic
and telephone historyvisits. To assess the global overall severity of dyspeptic psia symptoms, a seven
point Likert- type scale will beis used, which will to allow each patient to express raise the severity of the
symptoms. Thise scale will beis raised fromby: (1) no problem to (7) very severe problem/-cannot be
ignored. , markedly limits daily activities, and often required rest.The specific of the scale will help to
attribute three criteria for use as outcome measures in clinical trials: reproducibility, responsiveness to
change and validity compared to corroborating measures. The scale is raised by: (1) no problem to (7)
very severe problem-cannot be ignored, markedly limits daily activities, and often required rest.
Also,All enrolled patients then will be asked to complete a the quality of life and gastrointestinal
symptom rating scale questionnaire for validation purposes. All costs will be included during the
treatment.. The dropout patients will be concluded as treatment failures and the evaluable patients data
will be tested and compared by the Cochran- Mantel- Haenszel test. The purpose of of these surveys will
aid us in determining any improvements of eliminating H. pylori in dyspeptic patients, additionally,
measuring the costs per patient comparing the success rate rate over the year of the study.is to measure
and describe the costs per patient over the year of the study.

Expected Results
In this project, we propose that a test for Helicobacter pylori and treat will prove beneficial to
those suffering from the pains of functional and uninvestigated dyspepsia. (Chiba et al., 2002). We are
currently equipped with the means necessary to eradicate H pylori and intend to apply this treatment to
alleviate the symptoms of dyspepsia. In order to determine the efficacy of H pylori identification
examinations, we will compare and contrast the Helisal rapid blood test and 13C-urea breath test; in
addition to using them to select patients for randomization. A recent study found that the 13C-urea breath
test was superior to the Helisal rapid blood test determining H pylori status. (Mowat et al., 1998).14 We
anticipate that the 13C-urea breath test will prove to be more efficient and less invasive than the Helisal
rapid blood test. Upon completion of the prescribed drug regimens, we hypothesize that the eradication of
H pylori will result in the improvement or cure of dyspepsia in patients with uninvestigated dyspepsia in
primary care. After one year of treatment, we anticipate to see a decrease of dyspepsia symptoms and
eradication of .H pylori. In addition, we expect to see an overall improvement in quality of life for
patients previously suffering from dyspepsia. Utilizing H. pylori eradication as a means of reducing
dyspepsia symptoms will also prove to limit the quantity of visits patients take to family practitioners, as
well as, a reduction in the amount of empirical drugs prescribed to patients with uninvestigated dyspepsia
(Chiba, Bernard, O'Brien, Goeree, & Hunt, 1998).9 In addition, we expect to see and overall reduction in
the average annual social healthcare cost involved in treating patients for dyspepsia.
Application
This project, which meets the standards and core values for the NSF, will significantly contribute
to the overall health and quality of life for the general public, as well as produce significant results for
downstream biomedical applications. Funding is critically important to enable successful detection and
treatment of this medical condition prior to carcinogenic stages. Exploring the relationship and impact
that H. pylori contributes to dyspepsia will allow us to develop more efficient and effective methods for
detecting and treating dyspepsia at minimal costs. Currently, dyspepsia affects up to 40% of the
population (Tougas, Chen, Hwang, Liu, & Eggleston, 1999) and has been found to interfere with and

limit daily activities.2 The results we expect to obtain from this research will directly contribute to
relieving the epigastric pain currently characterized by heartburn, acid regurgitation, abdominal bloating,
and nausea. Furthermore, this study may not only improve the symptoms of dyspepsia but also the overall
quality of life for these patients and their families. Verifying the test with 13C-urea breath test and treat to
eradicate H. pylori strategy will enable efficient detection and treatment for positive H. pylori patients
with uninvestigated dyspepsia in primary care. Funding this project will preface the developmental
applications in medical research and therapeutic treatments.

References - American Psychological Association (APA) citation

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Chiba, N., Bernard, L., O'Brien, B. J., Goeree, R., & Hunt, R. H. (1998). A Canadian physician

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Chiba N. Definitions of dyspepsia: time for a reappraisal. Eur J Surg (1998). 164(suppl 583):1423.

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Veldhuyzen van Zanten SJ, Flook N, Chiba N, Armstrong D, Barkun A, Bradette M, et al (2000). An

evidence-based approach to the management of uninvestigated dyspepsia in the era of Helicobacter

pylori. CMAJ, 162(suppl 12):S323.

5.

Mowat, C., Murray, L., Hilditch, T. E., Kelman, A., Oien, K., & McColl, K. E. (1998). Comparison

of helisal rapid blood test and 14C-urea breath test in determining Helicobacter pylori status and
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14.

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Biographical Sketch
Alyssa Bormann
I am currently studying Biochemistry at California State University, Fullerton. My relevant coursework
includes: Advanced Cellular Biology, Virology, and Immunology. I was previously studying the cellular
pathways and mechanisms of ionic manganese (i-Mn) in response to oxidative stress in the model
organism Caenorhabditis elegans. My previous experience with this particular subject matter involved
studying the effects of Helicobacter pylori infection on gastritis and peptic ulcers. I am a senior at CSUF
and expect to graduate in May 2016.
Nicholas Armada
I am currently studying Biochemistry at California State University Fullerton. I previously studied
aromatic systems and alkenes as radical traps for radicalized oxime and oxime ethers. I am currently
investigating the effects that H. pylori infections have on the gastrointestinal tract.

Stacy Guzman
My name is Stacy Guzman and I am currently researching uninvestigated dyspepsia at California State
University, Fullerton. My previous research involved studying the cyanobacterial morphological
structures of stromatolites.

Lien Phan
I am currently studying Molecular Cell Biology at California State University Fullerton. My previous
study was about FRED-based assay for the discovery of West Nile Virus protease inhibitor and I am
working on the uninvestigated dyspepsia cases.

Chiba, N. (1998). Definitions of dyspepsia: time for a reappraisal. Eur J Surg

Suppl(583), 14-23.
Veldhuyzen van Zanten, S. J., Flook, N., Chiba, N., Armstrong, D., Barkun, A.,
Bradette, M., et al. (2000). An evidence-based approach to the management of
uninvestigated dyspepsia in the era of Helicobacter pylori. Canadian Dyspepsia
Working Group. CMAJ, 162(12 Suppl), S3-23.

References (American Chemical Society Citation Style)

1.
Jones, R. H., Approaches to uninvestigated dyspepsia. Gut 2002, 50 Suppl 4,
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2.
Tougas, G.; Chen, Y.; Hwang, P.; Liu, M. M.; Eggleston, A., Prevalence and
impact of upper gastrointestinal symptoms in the Canadian population: findings
from the DIGEST study. Domestic/International Gastroenterology Surveillance Study.
In Am J Gastroenterol, United States, 1999; Vol. 94, pp 2845-54.
3.
Veldhuyzen van Zanten, S. J.; Flook, N.; Chiba, N.; Armstrong, D.; Barkun, A.;
Bradette, M.; Thomson, A.; Bursey, F.; Blackshaw, P.; Frail, D.; Sinclair, P., An
evidence-based approach to the management of uninvestigated dyspepsia in the
era of Helicobacter pylori. CMAJ 2000, 162 (12), S3-S23.
4.
Suzuki, H.; Nishizawa, T.; Hibi, T., Can Helicobacter pylori-associated
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26 Suppl 3, 42-5.
5.
Chiba, N.; Van Zanten, S. J.; Sinclair, P.; Ferguson, R. A.; Escobedo, S.; Grace,
E., Treating Helicobacter pylori infection in primary care patients with

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(7344), 1012-6.
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Talley, N. J.; Silverstein, M. D.; Agreus, L.; Nyren, O.; Sonnenberg, A.;
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Mock, T.; Yatscoff, R.; Foster, R.; Hyun, J. H.; Chung, I. S.; Shim, C. S.;
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Mowat, C.; Murray, L.; Hilditch, T. E.; Kelman, A.; Oien, K.; McColl, K. E.,
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Gastroenterol, United States, 1998; Vol. 93, pp 20-5.