Helicobacter Pylori Eradication Trial to Reduce Iron Deficiency in Children

For the last 12 years, scientific evidence has mounted linking Helicobacter pylori infection
with iron deficiency and iron deficiency anemia. Reports from around the world on several
cases of iron deficiency anemia refractory to iron supplementation among children infected
with Helicobacter pylori, most without evident ulcers, clearly indicate that such cases have
been cured of their anemia after receiving a course of Helicobacter pylori eradication
therapy. Several studies based on national surveys, including one on the U.S. National Health
and Nutrition Examination Survey data and conducted by the authors of this proposal, have
found an association between Helicobacter pylori infection and the levels of iron stores.
However, these studies fail to demonstrate that anemia follows Helicobacter pylori infection.
Moreover, most previous research has been conducted outside of the contiguous U.S. and has
not included young children, one of the high-risk populations for iron deficiency and iron
deficiency anemia. Data on this age-group is most needed to develop sound public health
interventions.

We propose to conduct such a study among children living in El Paso, Texas, a city located on
the U.S.-Mexico border. A series of studies have been conducted in that city by the authors
of this proposal, including a National Institutes of Health sponsored study aiming to
describe the natural history of Helicobacter pylori infection in children from birth to age
seven years (84 months). We hypothesize that the Helicobacter pylori bacterium decreases iron
from the stomach and that this effect of the infection can be identified among persons with
iron deficiency as well as among persons with normal iron stores. Currently, the clinical
management of the most extreme form of iron deficiency, that is iron deficiency anemia,
relies only on supplemental iron therapy. For ethical reasons, our study will identify
children with anemia from the study, and will assign them to one of the arms receiving iron
supplementation. Our study will determine whether a combination of iron supplementation and
sequential Helicobacter pylori eradication therapy yields higher increases of iron stores
than each of these treatments alone. To summarize, our main hypothesis is that Helicobacter
pylori infection is associated with iron deficiency such that Helicobacter pylori eradication
would result in an increase in the levels of:

1. serum ferritin,

2. transferrin saturation, and

3. hemoglobin.

To test these hypotheses we will randomly assign 125 Helicobacter pylori-infected children (3
to 10 years of age) into each of the following four groups: Helicobacter pylori eradication
treatment, iron supplementation, Helicobacter pylori eradication plus iron supplementation,
or placebo. We plan to recruit infected children through a household survey in El Paso,
screen their Helicobacter pylori infection status by a stool test, and invite their parents
to undergo a confirmatory breath test. Infected children randomly allocated to those four
arms of the study will be followed closely during the 6 weeks they are taking the study
medication to record any adverse event, followed by a visit at 45 days after treatment to
tell whether or not those receiving the medication had their infection eradicated, between 6
and 12 months for hematological evaluation to compare with the baseline levels of iron
stores.

Inclusion Criteria:

- Children 3-10 years of age

- Helicobacter pylori infected, asymptomatic

- Healthy otherwise

- Parents provided consent/assenting children 7-10 years of age

Exclusion Criteria:

- Parental consent or child assent not obtained

- History of antibiotic-related allergic episodes

- Children with a history of allergy, asthma, hay fever or urticaria

- Phenylketonurics

- Abnormal renal and hepatic functions as evaluated through albumin, bilirubin, AST (or
SGOT), ALT (or SGPT), alkaline phosphatase and GGT-P

- History of peptic ulcer

- History of recent (< 1 month) severe disease

- History of recent (< 1 month) use of antibiotics, antacids, H2 receptor antagonists,
proton pump inhibitors and remedies containing bismuth

- Parents uncertain about staying in El Paso for the next year