Helicobacter Pylori Eradication Trial to Reduce Iron Deficiency in Children

NCT ID: NCT00364104

Last Updated: 2009-06-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 125 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-03-31
• Study Completion Date: 2008-12-31

Brief Summary

The investigators 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. The aim of this study is to determine whether Helicobacter pylori eradication in children is followed by an increase in markers of iron stores after six to twelve months of treatment.

Detailed Description

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.

Conditions

Iron Deficiency

Keywords

Iron deficiency; Helicobacter infection; Epidemiology

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

A

A 10-day course of Hp infection sequential eradication therapy plus 6-weeks of iron supplementation

Group Type: EXPERIMENTAL

Quadruple sequential Helicobacter pylori eradication + iron sulfate

Intervention Type: DRUG

A 10-day course of Hp infection sequential eradication therapy plus 6-weeks of iron supplementation

B

The 10-day course of Hp infection sequential eradication therapy only plus 6-weeks of matching placebo of iron supplementation

Group Type: EXPERIMENTAL

Quadruple sequential Helicobacter pylori eradication therapy

Intervention Type: DRUG

A 10-day course of Hp infection sequential eradication therapy only plus 6-weeks of matching placebo of iron supplementation

C

6-weeks of iron supplementation only plus 10-days of matching placebo of Hp infection eradication therapy

Group Type: EXPERIMENTAL

Ferrous sulfate

Intervention Type: DRUG

6-weeks of iron supplementation only plus 10-days matching placebo of Hp infection eradication therapy

D

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo only (10-days of matching placebo of Hp eradication therapy and 6-weeks of matching iron supplementation).

Interventions

Quadruple sequential Helicobacter pylori eradication + iron sulfate

A 10-day course of Hp infection sequential eradication therapy plus 6-weeks of iron supplementation

Intervention Type: DRUG

Quadruple sequential Helicobacter pylori eradication therapy

A 10-day course of Hp infection sequential eradication therapy only plus 6-weeks of matching placebo of iron supplementation

Intervention Type: DRUG

Ferrous sulfate

6-weeks of iron supplementation only plus 10-days matching placebo of Hp infection eradication therapy

Intervention Type: DRUG

Placebo

Placebo only (10-days of matching placebo of Hp eradication therapy and 6-weeks of matching iron supplementation).

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 36 Months
• Maximum Eligible Age: 120 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Texas Tech University

OTHER

Sponsor Role: collaborator

University of Texas

OTHER

Sponsor Role: collaborator

Baylor College of Medicine

OTHER

Sponsor Role: collaborator

University of North Texas Health Science Center

OTHER

Sponsor Role: collaborator

The University of Texas Health Science Center, Houston

OTHER

Sponsor Role: lead

Responsible Party

UT Houston HSC School of Public Health El Paso Regional Campus

Principal Investigators

Victor M Cardenas, MD, MPH, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Texas-Houston School of Public Health El Paso Regional Campus

Locations

Texas Tech University School of Medicine

El Paso, Texas, United States

Countries

United States

References

Cardenas VM, Prieto-Jimenez CA, Mulla ZD, Rivera JO, Dominguez DC, Graham DY, Ortiz M. Helicobacter pylori eradication and change in markers of iron stores among non-iron-deficient children in El Paso, Texas: an etiologic intervention study. J Pediatr Gastroenterol Nutr. 2011 Mar;52(3):326-32. doi: 10.1097/MPG.0b013e3182054123.

Reference Type: DERIVED

PMID: 21336159 (View on PubMed)

Prieto-Jimenez CA, Cardenas VM, Fischbach LA, Mulla ZD, Rivera JO, Dominguez DC, Graham DY, Ortiz M. Double-blind randomized trial of quadruple sequential Helicobacter pylori eradication therapy in asymptomatic infected children in El Paso, Texas. J Pediatr Gastroenterol Nutr. 2011 Mar;52(3):319-25. doi: 10.1097/MPG.0b013e318206870e.

Reference Type: DERIVED

PMID: 21336156 (View on PubMed)

Other Identifiers

HSC-SPH-06-0374

Identifier Type: -

Identifier Source: org_study_id