Potential of Prebiotic Galacto-oligosaccharides in Improving Efficacy and Safety of Oral Iron Supplementation in HIV-infected Children

NCT ID: NCT04931641

Last Updated: 2025-03-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 86 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-01
• Study Completion Date: 2022-10-04

Brief Summary

The objectives of this randomized controlled trial in virally suppressed HIV-positive children with anemia and/or depleted iron stores are to determine the effect of prebiotic galacto-oligosaccharides (GOS) as adjunct treatment to 12 weeks of oral iron supplementation on:

1. iron status measured by conventional iron status biomarkers,

2. fractional absorption of iron (fraction of total body iron per day, measured as Kabs, the slope of 57Fe isotopic dilution) and mean total amount of iron absorbed each day (mg Fe/day, calculated as Kabs x mean total body iron),

3. systemic and gut inflammation, as well as gut mucosal integrity,

4. gut microbiome composition, and

5. adverse effects and gastrointestinal side-effects.

Detailed Description

Iron deficiency anemia (IDA) in childhood can impair growth and cognition, as well as reduce school performance. Furthermore, anemia frequently complicates pediatric HIV infection and predicts disease progression and mortality. However, there is no international consensus on the treatment of ID and IDA in HIV-infected children, because of concerns around the efficacy and safety of oral iron supplements. Recent studies have suggested that oral iron supplements may increase gut inflammation in African children. This could be particularly detrimental in HIV-infected children, who may have gut immune activation, enteropathy and adverse shifts in the gut microbiome.

Previous stable iron isotope studies from the ETH Laboratory of Human Nutrition showed that the consumption of prebiotic galacto-oligosaccharides (GOS) together with supplemental doses of iron can increase iron absorption. In Kenyan infants, we further showed that the addition of GOS to an iron-containing micronutrient powder mitigated the adverse effects of iron on the gut microbiome.

Thus, we hypothesize that providing GOS as adjunct treatment to oral iron supplementation will improve efficacy (iron absorption and iron status), reduce systemic and gut inflammation, improve mucosal integrity, and mitigated iron-induced alterations in the gut microbiome, adverse events and gastrointestinal side-effects in virally suppressed HIV-infected children.

Conditions

Iron Deficiency; HIV

Study Design

• Allocation Method: NA
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

50 mg oral iron as ferrous fumarate (FeFum) with 7.5 g galacto-oligosaccharides

Group Type: EXPERIMENTAL

Galacto-oligosaccharides

Intervention Type: DIETARY_SUPPLEMENT

Prebiotic galacto-oligosaccharides (GOS)

Ferrous fumarate

Intervention Type: DIETARY_SUPPLEMENT

50 mg iron as ferrous fumarate

50 mg oral iron as ferrous fumarate (FeFum) with 7.5 g maltodextrin

Group Type: PLACEBO_COMPARATOR

Maltodextrin

Intervention Type: OTHER

Maltodextrin (placebo)

Ferrous fumarate

Intervention Type: DIETARY_SUPPLEMENT

50 mg iron as ferrous fumarate

Interventions

Galacto-oligosaccharides

Prebiotic galacto-oligosaccharides (GOS)

Intervention Type: DIETARY_SUPPLEMENT

Maltodextrin

Maltodextrin (placebo)

Intervention Type: OTHER

Ferrous fumarate

50 mg iron as ferrous fumarate

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

Prebiotic

Eligibility Criteria

Inclusion Criteria

• Age 10-15 years at baseline;
• Mild to moderate micro- and normocytic anaemia defined as Hb ≥8.0 and <11.5 / 12 g/dL (children 10-11 / 12-15 years) plus mean corpuscular volume ≤91.5 fL and/or iron deficiency defined as ferritin <30 µg/L or sTfR >8.3 mg/L;
• Body-Mass-Index-for-age Z-scores (BAZ) -3 to 2 SD of reference population;
• HIV criteria: HIV RNA viral load <50 copies/mL (measured as part of routine care);
• Willingness of caregiver to participate in the study;
• 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 area for the period of the study.

Exclusion Criteria

• Child received iron supplements or antibiotic treatment 3 months prior to study start;
• 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 involving medical or physical interventions.

• Minimum Eligible Age: 10 Years
• Maximum Eligible Age: 15 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Stellenbosch

OTHER

Sponsor Role: collaborator

Swiss Federal Institute of Technology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jeannine Baumgartner, PhD

Role: PRINCIPAL_INVESTIGATOR

Swiss Federal Institute of Technology

Michael Zimmermann, MD

Role: STUDY_CHAIR

Swiss Federal Institute of Technology

Locations

Familiy Clinical Research Unit (FAMCRU)

Cape Town, , South Africa

Countries

South Africa

Other Identifiers

Fe-GOS-HIV

Identifier Type: -

Identifier Source: org_study_id