TuberculosisNCT02176772
Iron Absorption and Utilization During Tuberculosis and After Treatment
An observational study of Tuberculosis, run by Swiss Federal Institute of Technology at 1 site in Tanzania.
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. Read more about this study
- Who is it for?
- Ages 18 to 45 years
- Conditions the study is for
- Tuberculosis
- What is being tested?
- Stable iron isotopes, non-drug intervention
- How many people
- 19 participants
- Where
- 1 siteTanzania
- Study dates
- Apr 2015to Jan 2017
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- No healthy volunteers
- Adult
Study population: 18 tuberculosis cases recruited at the Bagamoyo District Hospital and surrounding TB diagnostic centres.
Who may be able to join
- Females and males 18-45 years of age
- Sputum smear-positive, and confirmed by polymerase chain reaction and culture
- Obtained informed consent
Who cannot join
- 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
Show all 9Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
Tanzania1 site
Tb-clinic, Bagamoyo Research and Training Centre
Bagamoyo, Pwani Region, 0601
About this study
Official title: The Effects of Tuberculosis on Dietary Iron Absorption and Systemic Iron Utilization: a Double Stable Isotope Study in Bagamoyo, Tanzania
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.
Read more
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.
- Conditions
- Tuberculosis
- Being tested
- Stable iron isotopes, non-drug intervention
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stable iron isotopes, non-drug interventionOther
| Study group | Role | What they receive |
|---|---|---|
| Tuberculosis, no HIV and severe anemia | Not described Receives: Other: Stable iron isotopes, non-drug intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: baseline, 8 weeks
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.
Measured: baseline, 8 weeks
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
Measured: baseline, 24 weeks
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.
Measured: baseline, 24 weeks
Secondary outcomes (13)
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.
Measured: baseline, 2 weeks
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.
Measured: baseline, 4 weeks
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.
Measured: baseline, 6 weeks
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.
Measured: baseline, 8 weeks
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.
Measured: baseline, 10 weeks
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.
Measured: baseline, 12 weeks
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.
Measured: baseline, 14 weeks
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.
Measured: baseline, 16 weeks
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.
Measured: baseline, 18 weeks
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.
Measured: baseline, 20 weeks
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.
Measured: baseline, 22 weeks
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.
Measured: baseline, 24 weeks
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.
Measured: baseline, 26 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2014 (estimated)
- Study startApr 2015
- Primary completionJan 2017
- Study completionJan 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case crossover
- Time perspective
- Prospective
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Swiss Federal Institute of Technology
- Sponsor type
- University, hospital or other
- Collaborators
- Ifakara Health Institute, Swiss Tropical & Public Health Institute
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02176772
- Sponsor's protocol ID
- Fe_TB_Study_TZ
- Status last verified
- Jun 2017
- First submitted
- 23 Jun 2014
- Last updated
- 5 Jun 2017
- Results posted
- No
Publications
Cercamondi CI, Stoffel NU, Moretti D, Zoller T, Swinkels DW, Zeder C, Mhimibra F, Hella J, Fenner L, Zimmermann MB. Iron homeostasis during anemia of inflammation: a prospective study of patients with tuberculosis. Blood. 2021 Oct 14;138(15):1293-1303. doi: 10.1182/blood.2020010562.
PubMed 33876222
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Tuberculosis on Dietary Iron Absorption and Systemic Iron Utilization: a Double Stable Isotope Study in Bagamoyo, Tanzania
- ClinicalTrials.gov ID
- NCT02176772
- Acronym / sponsor ID
- Fe_TB_Study_TZ
- Conditions
- Tuberculosis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Swiss Federal Institute of TechnologyUniversity, hospital or other
- Collaborators
- Ifakara Health Institute, Swiss Tropical & Public Health Institute
- Study start
- Apr 2015
- Primary completion
- Jan 2017 (actual)
- Study completion
- Jan 2017 (actual)
- First posted
- 27 Jun 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case crossover
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tuberculosis, no HIV and severe anemia | – | Other: Stable iron isotopes, non-drug intervention |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- 18 tuberculosis cases recruited at the Bagamoyo District Hospital and surrounding TB diagnostic centres.
Key inclusion criteria (3 listed)
- Females and males 18-45 years of age
- Sputum smear-positive, and confirmed by polymerase chain reaction and culture
- Obtained informed consent
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Stable iron isotopes, non-drug intervention | Other | Tuberculosis, no HIV and severe anemia |
Primary outcome
Change from baseline in iron absorption of stable isotope tracers at week 8
Time frame: baseline, 8 weeks
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
Change from baseline in iron incorporation of stable isotope tracers at week 8
Time frame: baseline, 8 weeks
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.
Change from baseline in iron absorption of stable isotope tracers at week 24
Time frame: baseline, 24 weeks
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
Change from baseline in iron incorporation of stable isotope tracers at week 24
Time frame: baseline, 24 weeks
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.
13 secondary outcomes
Change from baseline in serum hepcidin at week 2
Time frame: baseline, 2 weeks
Change from baseline in serum hepcidin at week 4
Time frame: baseline, 4 weeks
Change from baseline in serum hepcidin at week 6
Time frame: baseline, 6 weeks
Change from baseline in serum hepcidin at week 8
Time frame: baseline, 8 weeks
Change from baseline in serum hepcidin at week 10
Time frame: baseline, 10 weeks
Change from baseline in serum hepcidin at week 12
Time frame: baseline, 12 weeks
Change from baseline in serum hepcidin at week 14
Time frame: baseline, 14 weeks
Change from baseline in serum hepcidin at week 16
Time frame: baseline, 16 weeks
Change from baseline in serum hepcidin at week 18
Time frame: baseline, 18 weeks
Change from baseline in serum hepcidin at week 20
Time frame: baseline, 20 weeks
Change from baseline in serum hepcidin at week 22
Time frame: baseline, 22 weeks
Change from baseline in serum hepcidin at week 24
Time frame: baseline, 24 weeks
Change from baseline in serum hepcidin at week 26
Time frame: baseline, 26 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2017.
- Derived from this study: PubMed 33876222Cercamondi CI, Stoffel NU, Moretti D, Zoller T, Swinkels DW, Zeder C, Mhimibra F, Hella J, Fenner L, Zimmermann MB. Iron homeostasis during anemia of inflammation: a prospective study of patients with tuberculosis. Blood. 2021 Oct 14;138(15):1293-1303. doi: 10.1182/blood.2020010562.
Related trials for Tuberculosis
RecruitingPhase 2
Evaluating the Safety and Immunogenicity of MTBVAC
HIV I Infection, Tuberculosis
RecruitingObservational study
Training Protocol on the Natural History of Tuberculosis
Mycobacterium Infections, Tuberculosis, Multidrug-Resistant
RecruitingObservational study
Molecular Epidemiology, Strains Genotyping of Multi-drug Resistant Tuberculosis Circulating in Central Africa Region
Multidrug-resistant Tuberculosis (MDR-TB)
Active, not recruitingPhase 2
A Study to Evaluate the Efficacy, Safety and Immunogenicity of MTBVAC in Adolescents and Adults Living in a TB Endemic Region.
Tuberculosis (TB)
Active, not recruitingObservational study
Mycobacterial and Opportunistic Infections in HIV-Negative Thai and Taiwanese Patients Associated With Autoantibodies to Interferon-gamma
Nontuberculous Mycobacteria, Mycobacterium Tuberculosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Tuberculosis, run by Swiss Federal Institute of Technology at 1 site in Tanzania.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Tanzania. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline in iron absorption of stable isotope tracers at week 8 (time frame: baseline, 8 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02176772, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jun 2017.