Iron Absorption and Utilization During Tuberculosis and After Treatment

Tuberculosis Clinical Trial

Official title:

The Effects of Tuberculosis on Dietary Iron Absorption and Systemic Iron Utilization: a Double Stable Isotope Study in Bagamoyo, Tanzania

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02176772
• Other study ID #: Fe_TB_Study_TZ
• Status: Completed
• Phase: N/A
• First received: June 23, 2014
• Last updated: June 2, 2017
• Start date: April 2015
• Est. completion date: January 2017

Study information

• Verified date: June 2017
• Source: Swiss Federal Institute of Technology
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Background: The disease burden of tuberculosis (TB), second only to HIV/AIDS among infectious diseases, is a major public health problem in developing countries. Accumulating evidence suggests that iron status is a primary determinant of TB progression. Anaemia is prevalent in patients with TB, particularly in sub-Saharan Africa, and associated with increased mortality. Anaemia in TB may be due to inflammation, dietary iron deficiency, or both, and distinguishing among these aetiologies is difficult. Iron supplementation is commonly used to treat anaemia in TB patients, but may be unnecessary if inflammation is the cause. Body iron sequestered by TB inflammation can be mobilized during treatment and used to correct the anaemia. Moreover, supplemental iron may be retained within macrophages, potentially increasing susceptibility to TB and leading to a poorer clinical outcome. Thus, better understanding of iron metabolism during TB and the aetiology of TB-related anaemia would clarify the potential role of iron in pathogenesis and optimal management of the disease.

The investigators hypothesize that: a) TB will increase circulating hepcidin and thereby impair dietary iron absorption and systemic utilization of iron, resulting in iron sequestration and anaemia; b) TB treatment and resolution of inflammation over 6 months will decrease circulating hepcidin, correcting these impairments and improving iron status and hemoglobin; c) the majority of iron utilized to replenish hemoglobin during recovery from TB will come from mobilization of sequestered iron stores rather than from iron absorption.

Objectives: Use iron stable isotopes to characterize iron balance over six months of TB treatment, and specifically to: a) quantify oral and intravenous iron incorporation (oral absorption and systemic iron utilization) at three time points during TB treatment (acute disease, after the intensive treatment phase and at completion of the continuation treatment phase); and b) determine the effect of treatment on iron mobilization from stores to replenish hemoglobin.

Methods/Subjects: Using a triple stable-isotope technique, iron absorption from labelled test meals (57Fe) and systemic iron utilization after labelled intravenous doses (54Fe, 58Fe) will be determined in 18 Tanzanian subjects with newly diagnosed pulmonary TB. The subjects will be studied at three time points (i) the day after TB diagnosis while infected, (ii) after 8 weeks of intensive phase treatment, and (iii) after another 16 weeks of continuation phase treatment. Iron status, hemoglobin, hepcidin and inflammation indexes will be measured at each time point. Isotope enrichment during the two treatment phases will be measured to estimate the relative rates of iron absorption and mobilization from stores during the intensive and continuation phases to determine the relative contributions of iron absorption and iron mobilization from stores during TB treatment and recovery.

Outcome: These studies will provide important new insights into the aetiology of anaemia and iron metabolism in TB patients. The results will provide essential data for evidence-based recommendations on the timing, administration route and efficacy of iron therapy in patients with TB, making possible, a safer and more effective treatment of anaemia in TB while decreasing morbidity and mortality from the disease.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: January 2017
• Est. primary completion date: January 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• Females and males 18-45 years of age

• Sputum smear-positive, and confirmed by polymerase chain reaction and culture

• Obtained informed consent

Exclusion Criteria:

• Pregnancy or Lactating (assessed by pregnancy test)

• Body weight <40 kg

• Severe anaemia (Hb <70 g/L)

• HIV positive (assessed by HIV test)

• Positive rapid malaria antigen test

• Intake of mineral/vitamin supplements 2 weeks before and during the study

• Diagnosed metabolic or gastrointestinal disorders, eating disorders or food allergy

• Blood transfusion, blood donation or significant blood loss (accident, surgery) over the past 6 months

• Subject who cannot be expected to comply with study protocol (e.g. non-residents to the Bagamoyo Coast region, or subjects who plan to travel or move)

Related Conditions & MeSH terms

• Tuberculosis

Intervention

Other:
• Stable iron isotopes, non-drug intervention

Locations

Country	Name	City	State
Tanzania	Tb-clinic, Bagamoyo Research and Training Centre	Bagamoyo	Pwani

Sponsors (3)

Lead Sponsor	Collaborator
Swiss Federal Institute of Technology	Ifakara Health Institute, Swiss Tropical & Public Health Institute

Country where clinical trial is conducted

Tanzania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in iron absorption of stable isotope tracers at week 8	Stable iron isotopes will be orally administered under standardized conditions and close supervision. Iron absorption will be calculated from the shift in the normal isotopic abundance in red blood cells; 8 weeks = end of first treatment phase	baseline, 8 weeks
Primary	Change from baseline in iron incorporation of stable isotope tracers at week 8	Stable iron isotopes will be infused under standardized conditions and close supervision. Iron incorporation will be calculated from the shift in the normal isotopic abundance in red blood cells; 8 weeks = end of first treatment phase.	baseline, 8 weeks
Primary	Change from baseline in iron absorption of stable isotope tracers at week 24	Stable iron isotopes will be orally administered under standardized conditions and close supervision. Iron absorption will be calculated from the shift in the normal isotopic abundance in red blood cells; 24 weeks = end of second treatment phase	baseline, 24 weeks
Primary	Change from baseline in iron incorporation of stable isotope tracers at week 24	Stable iron isotopes will be infused under standardized conditions and close supervision. Iron incorporation will be calculated from the shift in the normal isotopic abundance in red blood cells; 24 weeks = end of second treatment phase.	baseline, 24 weeks
Secondary	Change from baseline in serum hepcidin at week 2	As a determinant of iron metabolism, serum hepcidin will be measured several times during the study.	baseline, 2 weeks
Secondary	Change from baseline in serum hepcidin at week 4	As a determinant of iron metabolism, serum hepcidin will be measured several times during the study.	baseline, 4 weeks
Secondary	Change from baseline in serum hepcidin at week 6	As a determinant of iron metabolism, serum hepcidin will be measured several times during the study.	baseline, 6 weeks
Secondary	Change from baseline in serum hepcidin at week 8	As a determinant of iron metabolism, serum hepcidin will be measured several times during the study.	baseline, 8 weeks
Secondary	Change from baseline in serum hepcidin at week 10	As a determinant of iron metabolism, serum hepcidin will be measured several times during the study.	baseline, 10 weeks
Secondary	Change from baseline in serum hepcidin at week 12	As a determinant of iron metabolism, serum hepcidin will be measured several times during the study.	baseline, 12 weeks
Secondary	Change from baseline in serum hepcidin at week 14	As a determinant of iron metabolism, serum hepcidin will be measured several times during the study.	baseline, 14 weeks
Secondary	Change from baseline in serum hepcidin at week 16	As a determinant of iron metabolism, serum hepcidin will be measured several times during the study.	baseline, 16 weeks
Secondary	Change from baseline in serum hepcidin at week 18	As a determinant of iron metabolism, serum hepcidin will be measured several times during the study.	baseline, 18 weeks
Secondary	Change from baseline in serum hepcidin at week 20	As a determinant of iron metabolism, serum hepcidin will be measured several times during the study.	baseline, 20 weeks
Secondary	Change from baseline in serum hepcidin at week 22	As a determinant of iron metabolism, serum hepcidin will be measured several times during the study.	baseline, 22 weeks
Secondary	Change from baseline in serum hepcidin at week 24	As a determinant of iron metabolism, serum hepcidin will be measured several times during the study.	baseline, 24 weeks
Secondary	Change from baseline in serum hepcidin at week 26	As a determinant of iron metabolism, serum hepcidin will be measured several times during the study.	baseline, 26 weeks