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

HIV Clinical Trial

Official title:

Improving Efficacy and Safety of Oral Iron Supplementation in HIV-infected Children by Providing Prebiotic Galacto-oligosaccharides as Adjunct Treatment: A Randomized Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04931641
• Other study ID #: Fe-GOS-HIV
• Status: Recruiting
• Phase: N/A
• Start date: August 1, 2021
• Est. completion date: December 1, 2022

Study information

• Verified date: January 2022
• Source: Swiss Federal Institute of Technology
• Contact: Jeannine Baumgartner, PhD
• Phone: +41446328634
• Email: jeannine.baumgartner[@]hest.ethz.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 1, 2022
• Est. primary completion date: April 1, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 10 Years to 15 Years

Eligibility

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.

Related Conditions & MeSH terms

• Anemia, Iron-Deficiency
• HIV
• Iron Deficiency

Intervention

Dietary Supplement:
• Galacto-oligosaccharides
Prebiotic galacto-oligosaccharides (GOS)

Other:
• Maltodextrin
Maltodextrin (placebo)

Dietary Supplement:
• Ferrous fumarate
50 mg iron as ferrous fumarate

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	Iron status: Serum Ferritin (ug/L) (SF)	Change in SF concentrations over the study period of 12 weeks	0, 6, 12 weeks
Primary	Iron status: Soluble Transferrin Receptor (mg/L) (sTfR)	Change in sTfR concentrations over the study period of 12 weeks	0, 6, 12 weeks
Primary	Iron status: Transferrin saturation (%) (Tsat)	Change in Tsat concentrations over the study period of 12 weeks	0, 6, 12 weeks
Primary	Iron status: Hemoglobin (g/dL) (Hb)	Change in Hb concentrations over the study period of 12 weeks	0, 6, 12 weeks
Primary	Fractional iron absorption	Fractional absorption of iron will be determined by measuring Kabs, the slope of 57Fe isotopic dilution over the study period. From this value, mean total amount of iron absorbed each day (mg Fe/day, calculated as Kabs x mean total body iron) can be estimated.	0, 6, 12 weeks
Secondary	Systemic inflammation: C-reactive protein (mg/L) (CRP)	Change in CRP concentrations over the study period of 12 weeks	0, 6, 12 weeks
Secondary	Systemic inflammation: Alpha-1-acid glycoprotein (g/L) (AGP)	Change in AGP concentrations over the study period of 12 weeks	0, 6, 12 weeks
Secondary	Hepcidin (nM)	Change in hepcidin concentrations over the study period of 12 weeks	0, 6, 12 weeks
Secondary	Gut inflammation: Intestinal fatty acids binding protein (ng/ml) (IFABP)	Change in IFABP concentrations from baseline (0 weeks) to endpoint (12 weeks)	0 and 12 weeks
Secondary	Gut inflammation: Fecal calprotectin (µg/g)	Change in fecal calprotectin concentrations from baseline (0 weeks) to endpoint (12 weeks)	0 and 12 weeks
Secondary	Gut inflammation: Myeloperoxidase (µg /mL) (MPO)	Change in MPO concentrations from baseline (0 weeks) to endpoint (12 weeks)	0 and 12 weeks
Secondary	Gut microbiome composition	Change in gut microbiome composition from baseline (0 weeks) to endpoint (12 weeks)	0 and 12 weeks
Secondary	Fecal pH	Change in fecal pH from baseline (0 weeks) to endpoint (12 weeks)	0 and 12 weeks
Secondary	HIV viral load (copies/ml)	Change in HIV viral load from baseline (0 weeks) to endpoint (12 weeks)	0 and 12 weeks
Secondary	Gastrointestinal and respiratory symptoms	Self-reported gastrointestinal and respiratory symptoms assessed using a symptoms diary over the study period of 12 weeks	12 weeks