Clinical trial NCT04931641: Potential of Prebiotic Galacto-oligosaccharides in Improving Efficacy and Safety of Oral Iron Supplementation in HIV-infected Children
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Iron Deficiency
HIV
Lead sponsor: Swiss Federal Institute of Technology
Sponsor class: OTHER
Collaborators: name: University of Stellenbosch
First posted: 2021-06-18
Enrollment: 86
Sex: ALL
Minimum age (years): 10
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: PARALLEL
Intervention model description: Randomized controlled trial
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Iron status: Serum Ferritin (ug/L) (SF)
timeFrame: 0, 6, 12 weeks
measure: Iron status: Soluble Transferrin Receptor (mg/L) (sTfR)
timeFrame: 0, 6, 12 weeks
measure: Iron status: Transferrin saturation (%) (Tsat)
timeFrame: 0, 6, 12 weeks
measure: Iron status: Hemoglobin (g/dL) (Hb)
timeFrame: 0, 6, 12 weeks
measure: Fractional iron absorption
timeFrame: 0, 6, 12 weeks
Secondary outcomes:
measure: Systemic inflammation: C-reactive protein (mg/L) (CRP)
timeFrame: 0, 6, 12 weeks
measure: Systemic inflammation: Alpha-1-acid glycoprotein (g/L) (AGP)
timeFrame: 0, 6, 12 weeks
measure: Hepcidin (nM)
timeFrame: 0, 6, 12 weeks
measure: Gut inflammation: Intestinal fatty acids binding protein (ng/ml) (IFABP)
timeFrame: 0 and 12 weeks
measure: Gut inflammation: Fecal calprotectin (µg/g)
timeFrame: 0 and 12 weeks
measure: Gut inflammation: Myeloperoxidase (µg /mL) (MPO)
timeFrame: 0 and 12 weeks
measure: Gut microbiome composition
timeFrame: 0 and 12 weeks
measure: Fecal pH
timeFrame: 0 and 12 weeks
measure: HIV viral load (copies/ml)
timeFrame: 0 and 12 weeks
measure: Gastrointestinal and respiratory symptoms
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Cape Town
country: South Africa
facility: Familiy Clinical Research Unit (FAMCRU)
Study officials:
affiliation: Swiss Federal Institute of Technology
name: Jeannine Baumgartner, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Swiss Federal Institute of Technology
name: Michael Zimmermann, MD
role: STUDY_CHAIR
References: