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
Many primary care patients suffer from uninvestigated dyspepsia and often require urgent relief
from symptoms.1 Further analysis of the involvement of Helicobacter pylori (H. pylori) with
uninvestigated dyspepsia could reduce any alarming symptoms and provide individualized treatment for
H. pylori-infected patients. A Helisal rapid blood test and a 13C-urea breath test will be used to screen
patients that are positive for H. pylori. We hypothesize that the eradication of H. pylori will result in the
improvement or cure of primary care patients with uninvestigated dyspepsia at a minimal cost.
Searchable Keywords: Uninvestigated dyspepsia, H. pylori, 13C-urea breath test, Helisal blood test, PPI.
Introduction
Dyspepsia, commonly known as indigestion, continues to negatively impact the lives of more
than a third of the general population, most of which are patients in primary care. 2 Such patients are prone
to structural diseases such as: ulcer cancer, malignancy, and peptic ulcer disease. 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. 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, heartburn, excessive burning,
abdominal bloating, nausea, regurgitation, slow digestion, or satiety. 5 Patients experience prevailing
symptoms such as heartburn and regurgitation are likely diagnosed with gastroesophageal reflux disease
(GERD), and 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. 1 Patients with dyspepsia are
normally referred to a specialist and undergo a visual examination known as endoscopy. This nonsurgical
procedure has limitations in accurately evaluating dyspepsia and H. pylori. Furthermore, endoscopy is
accompanied with high healthcare costs and is linked with dangerous bacteria that can further infect
patients.6 Since dyspepsia is so prevalent and is associated with high healthcare costs, it is important to

find the most efficient method to detect the source of dyspepsia in primary care patients and completely
destroy the presence of the bacterium H. pylori.7
Objectives/Rationale
The causes and 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. Patients who visit their primary physician with complaints of dyspepsia are
often prescribed a series of proton-pump inhibitor (PPI) drugs 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.8 After attempting 2.5 courses of drug treatment, family practitioners usually move to further
investigating the cause.9 However, investigations remain ambiguous and the diagnosis put forward is
usually functional dyspepsia.10
A recommendation stating that a test and treat strategy on patients experiencing uninvestigated
dyspepsia may create significant symptom relief. However, it has not been previously explored in
randomized and controlled clinical trials. 11 Our laboratory plans to use a 13C-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 existing knowledge 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 simply 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 study. Patients will be eligible for the study if they are at
least 18 years or older and have suffered the symptoms of uninvestigated dyspepsia 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.12

The patients will be treated randomly twice daily for seven days, using the PPI omeprazole 20mg
for dyspepsia symptom relief, as well as antibiotics metronidazole 500mg and clarithromycin 250mg for
H. pylori eradication. A control group will be set up to take omeprazole 20mg along with placebo forms
of both antibiotics. We will use a Helisal rapid blood test and 13C-urea breath test to validate the patients
positive test results for H. pylori infection. We have chosen the Helisal rapid blood test and 13C-urea
breath tests over serological testing because serological testing requires specialty laboratory equipment.
Sending out samples to another lab for testing will greatly delay the study. The results of the rapid blood
test are available in ten minutes. This quick result time makes the test convenient for primary care
facilities to use. The Helikit for 13C-urea breath test will be used for initial screening for H. pylori
infection. This test is easy to use and is noninvasive since patients are only required to take a pill and
provide a breath sample.13
Patients who have experienced uninvestigated dyspepsia for 3 months or more and who also had
positive results for both H. pylori tests will be enrolled in computer randomization and assigned a
treatment group. This technique will eliminate any biased evaluation to allocate patients for seven days.
We will follow up with these patients every month for one year and record progress based on clinical and
telephone history. To assess the overall severity of dyspeptic symptoms, a seven point Likert- type scale
will be used, which will allow each patient to express the severity of the symptoms. This scale will be
raised from: (1) no problem to (7) very severe problem/cannot be ignored. Also, patients will be asked to
complete a quality of life and gastrointestinal symptom rating scale questionnaire for validation purposes.
The purpose of these surveys will aid us in determining any improvements of eliminating H. pylori in
dyspeptic patients, additionally, measuring the costs per patient success rate over the year of the study.
Expected Results
In this project, we propose that a test for H. pylori and eradicate strategy will prove beneficial
to those suffering from the pains of functional and uninvestigated dyspepsia. 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 in determining H. pylori status.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 the 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. 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 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 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. 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 future therapeutic treatments.

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 have taken the following
relevant courses: Cell Biology, Biochemistry, and Medicinal Chemistry. 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. I am a senior at CSUF and expect to
graduate in May 2016.
Stacy Guzman
I am a junior pursuing a degree in Cell and Developmental Biology at California State University,
Fullerton. My current research interests involve studying helicobacter pylori and its relationship with
peptic ulcer disease. Related coursework for this project includes: genetics, microbiology, and
immunology. My previous research studied cyanobacterial morphological structures of stromatolites. I
expect to graduate in May 2017.
Lien Phan
I am currently studying Molecular Cell Biology at California State University Fullerton. My relevant
courseworks are: Marine Biotechnology, Biochemistry, Pharmaceutical Biotechnology and Molecular
Cell Biology. My previous study was about FRED-based assay for the discovery of West Nile Virus
protease inhibitors. And I am working on the uninvestigated dyspepsia cases. As a senior CSUF student,
my expected graduation is on May 2016.

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