Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202009698591500 Date of Approval: 03/09/2020
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title Prebiotic GOS and lactoferrin for beneficial gut microbiota with iron supplements (PREFER)
Official scientific title Prebiotic galacto-oligosaccharides and lactoferrin for beneficial gut microbiota with iron supplements: an intervention trial in infants in Msambweni, Kwale County, southern coastal Kenya
Brief summary describing the background and objectives of the trial The ultimate goal of this research is to develop a means to safely administer iron supplements to infants in settings with high infection burden. The hypothesis underlying this project is that promoting development of a beneficial, protective gut microbiota by co-administration of prebiotic galacto-oligosaccharides (GOS) and iron-sequestering bovine lactoferrin (bLF) during iron supplementation will prevent iron-induced increases of opportunistic enteropathogens that cause infection and inflammation. The proposed research will extend our established strategy of conjoining investigations in vivo with intestinal fermentation and cellular models in vitro. We will conduct a randomized clinical trial in 6-month-old Kenyan infants in conjunction with mechanistic microbiota studies using our established long-term continuous polyfermenter platform inoculated with immobilized fecal microbiota from Kenyan infants. This research has two specific aims: 1) To conduct a randomized, controlled double-blind 9-month clinical trial in 6-month old Kenyan infants comparing the effects on gut microbiome composition among groups receiving in-home fortification for 6 months with micronutrient powders (MNPs) containing 5 mg iron (as ferrous fumarate [FeFum]) and (i) GOS (7.5 g), (ii) bLF (1 g), (iii) GOS (7.5 g) and bLF (1 g), and (iv) no GOS or bLF. Each infant will then be followed for an additional 3 months to determine the longer-term effects of the treatments. 2) To examine mechanisms of prebiotic GOS and bLF on microbiota composition, enteropathogen development, microbiota functions and metabolic activity, and inflammatory potential in vitro with treatments paralleling those in Specific Aim 1, using immobilized fecal microbiota from Kenyan infants to inoculate our established long-term continuous polyfermenter intestinal model (PolyFermS) to mimic Kenyan infant colon conditions, together with cellular studies.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) PREFER
Disease(s) or condition(s) being studied Nutritional, Metabolic, Endocrine
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Physical activity and nutrition
Anticipated trial start date 01/09/2019
Actual trial start date 26/01/2020
Anticipated date of last follow up 01/09/2023
Actual Last follow-up date 10/12/2021
Anticipated target sample size (number of participants) 288
Actual target sample size (number of participants) 288
Recruitment status Completed
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Stratified allocation where factors such as age, gender, center, or previous treatment are used in the stratification Sealed opaque envelopes Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Group C 1 sachet of 12.5 g of multiple micronutrient powders with 5 mg iron and 7.5 of galacto-oligosaccharides, and 1.0 g of bovine lactoferrin, every day 6 months The study group C will receive in-home fortification for 6 months with multiple micronutrient powders with 5 mg iron and Galacto-oligosaccharides, 7.5 g, and bovine lactoferrin, 1.0 g. 72
Experimental Group Group B 1 sachet of 12.5 g of multiple micronutrient powders with 5 mg iron and 1.0 g of Bovine lactoferrin, every day 6 months Study group B will receive in-home fortification for 6 months with multiple micronutrient powders with 5 mg iron and 1.0 g of Bovine lactoferrin 72
Experimental Group Group A 1 sachet of 12.5 g of multiple micronutrient powders with 5 mg iron and 7.5 g galacto-oligosaccharides, daily 6 months Study group A will receive in-home fortification for 6 months with multiple micronutrient powders with 5 mg iron and 7.5 g Galacto-oligosaccharides. 72
Control Group Group D 1 sachet of 12.5 g of multiple micronutrient powders with 5 mg iron and no galacto-oligosaccharides or bovine lactoferrin 6 months Study group D will receive in-home fortification for 6 months with multiple micronutrient powders with 5 mg iron. In this group, the usual maltodextrin carrier will be added to a weight of 10.0 g. 72 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
(i) delivery vaginally or by cesarean section, (ii) an infant age of 6 months (±3 weeks), (iii) mother ≥15 years of age, (iv) infant still breastfeeding, and (v) anticipated residence in the area for the study duration. (i) inability to provide informed consent, (ii) hemoglobin < 70 g/L, (iii) Z scores for weight-for-age (WAZ) or weight-for-height (WHZ) <3, (iv) any maternal or infant chronic illness, (v) administration of any vitamin or mineral supplements for the past 2 months, and (vi) any history of antibiotic treatment in the past seven days. Infant: 13 Month(s)-24 Month(s) 21 Week(s) 28 Week(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 28/09/2018 Columbia University IRB
Ethics Committee Address
Street address City Postal code Country
154 Haven Avenue, 1st Floor New York 10032 United States of America
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 09/03/2019 KEMRI SERU
Ethics Committee Address
Street address City Postal code Country
00200 OFF MBAGATHI ROAD, HOUSE NUMBER 8 Nairobi 54840 Kenya
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 01/03/2019 ETH Ethics
Ethics Committee Address
Street address City Postal code Country
Ramistrasse 101 Zurich 8092 Switzerland
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome The primary outcome measure will be the ratio of the abundances of potentially harmful (enteropathogenic and/or enterotoxigenic E. coli, C. difficile, members of the C. perfringens group, B. cereus, S. aureus, sum of Shigella spp., and Salmonella) to beneficial (bifidobacteria and the group of Lactobacillus/Leuconostoc/Pediococcus spp.) bacterial genera at 1 month. 1 month
Secondary Outcome The ratio of the abundances of potentially harmful to beneficial bacterial genera ratios and comparisons of microbiota composition at all time points, including assessment of effects of helminth infections. 1, 6 and 9 months
Secondary Outcome The prevalence of diarrhea, malaria, anemia, iron deficiency, iron deficiency anemia, inflammation, respiratory tract infections, and other illnesses. 1, 6, 9 months
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Msambweni County Referral Hospital Ukunda-Ramisi Road Ramisi Kwale Msambweni 8 0404 Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
National Institutes of Health 9000 Rockville Pike Bethesda Maryland 20892 United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor National Institute of Health 9000 Rockville Pike Bethesda Maryland 20892 United States of America Funding Agency
COLLABORATORS
Name Street address City Postal code Country
Simon Karanja School of Public Health, Kenyatta University Nairobi 43844 Kenya
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Gary Brittenham gmb31@cumc.columbia.edu 02123057005 3959 Broadway
City Postal code Country Position/Affiliation
New York 10032 United States of America Professor of Pediatrics at CUMC and NewYork Presbyterian Columbia University Irving Medical Center
Role Name Email Phone Street address
Public Enquiries Nicole Stoffel nicole.stoffel@hest.ethz.ch +41446328393 Schmelzbergstrasse 7
City Postal code Country Position/Affiliation
Zurich 8092 Switzerland Post Doc at ETH Zurich
Role Name Email Phone Street address
Scientific Enquiries Ambra Giorgetti ambra.giorgetti@hest.ethz.ch +41446328381 Schmelzbergstrasse 7
City Postal code Country Position/Affiliation
Zurich 8092 Switzerland PhD Student at ETH Zurich
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Individual participant data will not be available. We will report summary results of this clinical trial within a year from completion of the trial. Study Protocol Summary results of the clinical trial available for two years following the study completion Access to data to be requested to and controlled by the Clinical Trial Data and Safety Monitoring Board (DSMB) of the study.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information