Stable Iron Isotope Method in HIV+ and HIV- Children

Iron-deficiency Clinical Trial

Official title:

A Novel Stable Iron Isotope Method to Define Iron Needs and Improve Iron Nutrition in HIV+ and HIV- Children

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03572010
• Other study ID #: Fe_HIV
• Status: Completed
• Phase: N/A
• Start date: September 27, 2018
• Est. completion date: June 30, 2020

Study information

• Verified date: September 2021
• Source: Swiss Federal Institute of Technology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objective of this study is to compare HIV infected children to uninfected children regarding 1) quantifying iron absorption from iron fortified maize porridge, lipid-based food supplements and oral iron supplements, and 2) quantifying the daily iron requirement.

Description:

In Sub-Saharan Africa, HIV is a major cause of morbidity and mortality in children. Anemia frequently complicates pediatric HIV infection and predicts disease progression and mortality. Iron requirements and the specific contribution of iron deficiency (ID) to anemia in pediatric HIV infection remains uncertain. The fundamental barrier to understanding iron nutrition in HIV infection is that sub-clinical inflammation in individuals with HIV infection confounds the usual bio-markers used to assess iron status and response to iron interventions. A novel iron stable isotope technique developed by ETH Zurich, Switzerland, is a promising new tool for better understanding of iron metabolism in HIV infection. In contrast to existing conventional bio-markers of iron status, a method based on isotopic dilution of whole body iron labeled with stable, non-radioactive isotopes of iron (58Fe, 57Fe) could directly quantify iron requirements, as well as iron absorption from interventions, completely free of bias and confounding by inflammation. This method could offer, for the first time, a long-term quantitative measure of iron balance and absorption from iron interventions and provide reliable data on which to base nutrition recommendations for HIV infection.

The objective is to compare HIV infected children to uninfected children: 1) Quantify iron absorption from iron fortified maize porridge, lipid-based food supplements and oral iron supplements; 2) Quantify the daily iron requirement.

The study participants will be recruited from the South African Stellenbosch University/Tygerberg Children's Hospital long-term antiretroviral therapy (ART) cohort of perinatally HIV infected children and uninfected controls from the same communities, matched by age and gender. As a secondary outcome, we want to investigate the effect of iron supplementation on the gut microbiome.

In study 1, using a randomized cross-over design and stable isotope labeled single meal/doses the investigators will: a) quantify the impairment of dietary iron absorption in HIV infected, iron deficient children compared to HIV uninfected, iron deficient controls using a labeled iron fortified maize meal, a lipid-based nutritional supplement (LNS) and an oral iron supplement; and b) administer sufficient iron isotope label (57Fe) to allow equilibration and follow up of isotopic composition in the blood for two years (isotope dilution technique). At the end of Study 1, all iron deficient children will be iron replete prior to entering Study 2. In study 1, in parallel, a group of HIV infected and uninfected, iron sufficient children will be given orally 12 mg 57Fe as ferrous sulfate (FeSO4).

In study 2, the investigators will apply the principle of long-term isotope dilution to quantify the daily iron requirement in both the HIV infected and uninfected children, and the difference in iron requirements.

The overall goal is to provide optimized recommendations on dietary iron requirements and iron treatment regimens in HIV infected children, in order to reduce ID and anemia, improve their health and well-being, their long-term prognosis and quality of life.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 180
• Est. completion date: June 30, 2020
• Est. primary completion date: June 30, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 8 Years to 13 Years

Eligibility

Inclusion Criteria:

• Age 8-13 years at baseline

• Hemoglobin >=8 g/dL

• BMI -3 to 3 SD of reference population

• HIV criteria: soluble cluster of differentiation 4 (sCD4) >=500 cells/mm^3, HIV RNA viral load <50 copies/mL (measured as part of routine care)

• Plasma ferritin <30 mikrogramm/L

• The caregiver is willing to participate in the study

• The caregiver speaks English, Afrikaans or isiXhosa

• The informed consent form has been read and signed by the caregiver (or has been read out to the caregiver in case of illiteracy) plus assent needs to be obtained from the child

• Residence in the study site for the period of the study.

For non-iron deficient children:

• Hemoglobin >=11.5 g/dL

• Plasma ferritin >=40 mikrogramm/L

Exclusion Criteria:

• Iron supplements 3 months prior to study start

• Food allergy or intolerance against peanuts or milk

• Acute illness or other conditions that in the opinion of the PI or co-researchers would jeopardize the safety or rights of a participant in the trial or would render the participant unable to comply with the protocol

• Participants taking part in other studies requiring the drawing of blood

• Not planning long-term residence in study site.

Related Conditions & MeSH terms

• Anemia, Iron-Deficiency
• Iron-deficiency

Intervention

Dietary Supplement:
• FeFum fortified maize test meal
Maize porridge extrinsically labeled with 2 mg ferrous fumarate (58FeFum); only for iron deficient children (defined by plasma ferritin <40 mikrogramm/L and/or sTfR >8.3 mg/L); cereal staple foods, like maize, depending on milling, may be high in phytic acid, a potent iron absorption inhibitor
• FeSO4 fortified LNS
self-made Lipid-based nutritional supplement (LNS) extrinsically fortified and labeled with 6 mg ferrous sulfate (57FeSO4); only for iron deficient children (defined by plasma ferritin <40 mikrogramm/L and/or sTfR >8.3 mg/L); LNS may be a better food matrix for iron supplementation compared to maize-based porridge; contains canola oil, peanut paste, milk powder, sugar, maltodextrin and palm stearin
• FeSO4 supplement
170 mg iron tablets as FeSO4 (containing 55 mg of elemental iron) with 6 mg extrinsically labeled 57Fe; will be given together with a glass of water; only for iron deficient children (defined by plasma ferritin <40 mikrogramm/L and/or sTfR >8.3 mg/L);
• FeSO4 fortified fruit juice
Fruit juice labeled with 12 mg 57Fe as FeSO4; in the group for iron sufficient children

Locations

Country	Name	City	State
South Africa	Familiy Clinical Research Unit (FAMCRU)	Cape Town

Sponsors (2)

Lead Sponsor	Collaborator
Swiss Federal Institute of Technology	University of Stellenbosch

Country where clinical trial is conducted

South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Fractional iron absorption	Iron absorption will be measured from the 3 different types of iron vehicles from the iron deficient group (FeFum fortified maize porridge, FeSO4 containing LNS, FeSO4 supplement). It is estimated that iron absorption is lower in HIV infected children.	Measured 14 days after consumption of the 3 different types of iron vehicles (Days 17 and 31); Enrichment shift of iron isotopes into red blood cells from Day 31 to 451
Secondary	Hemoglobin in g/dL (in blood)	to identify anemia	Days -1, 17 (in iron deficient children), 31, 151, 271, 361, 451
Secondary	Plasma ferritin in µg/L (in blood)	to identify iron deficiency	Days -1, 17 (in iron deficient children), 31, 151, 271, 361, 451
Secondary	Soluble transferrin receptor in mg/L (in blood)	to identify iron deficiency	Days -1, 17 (in iron deficient children), 31, 151, 271, 361, 451
Secondary	Transferrin saturation in % (in blood)	to calculate percent of transferrin that has iron bound to it; Plasma iron and transferrin saturation will be combined to calculate transferrin saturation (ratio)	Days -1, 17 (in iron deficient children), 31, 151, 271, 361, 451
Secondary	Erythropoetin (in blood)	produced in kidney and triggers production of red blood cells	Days -1, 17 (in iron deficient children), 31, 151, 271, 361, 451
Secondary	C-reactive protein in mg/L (in blood)	to identify acute inflammation, which inhibits iron absorption	Days -1, 17 (in iron deficient children), 31, 151, 271, 361, 451
Secondary	alpha-1-glycoprotein in g/L (in blood)	to identify chronic inflammation, which inhibits iron absorption	Days -1, 17 (in iron deficient children), 31, 151, 271, 361, 451
Secondary	Plasma hepcidin (in blood)	one of major iron absorption regulators	Days -1, 17 (in iron deficient children), 31, 151, 271, 361, 451
Secondary	Interleukin-6 (in blood)	systemic inflammation marker	Days -1, 17 (in iron deficient children), 31, 151, 271, 361, 451
Secondary	Intestinal fatty acid binding protein 1 and 2 (in blood)	inflammation marker for gut integrity	Days -1, 17 (in iron deficient children), 31, 151, 271, 361, 451
Secondary	Lipopolysaccharide binding protein (in blood)	immune response marker	Days -1, 17 (in iron deficient children), 31, 151, 271, 361, 451
Secondary	Fecal calprotectin (in stool)	gut inflammation marker	Days -1, 31 and 121 (in iron deficient children)