Plain English Summary
Background and study aims
Stunting affects one of every four children globally, and is associated with delayed physical and cognitive development, and reduced working capacity and educational achievement. Childhood stunting therefore impairs human capital, and it may also increase the risk of chronic diseases later in life. Milk has been shown to play a role in growth, but it is not clear if such effects are due to the protein or to lactose and minerals (in whey permeate) in milk.
This study aims to assess the effects of milk protein and whey permeate in a lipid-based nutrient supplement (LNS) on growth in children with stunting.
Who can participate?
Children aged 12 – 59 months with stunted growth.
What does the study involve?
Participants will be randomly allocated to one of five groups. Groups 1 – 4 will receive a different LNS for 12-weeks, group 5 will not receive any supplement. Participants will be measured to assess growth over the 12 weeks as well as priding blood and stool samples.
What are the possible benefits and risks of participating?
It is expected that all children will benefit from the experimental products and/or the nutrition counselling, as well as the medical assessments and referrals, if needed. Apart from low risk of allergic reactions to milk or peanut, the products are not likely to pose any risks.
Where is the study run from?
1. Buwenge Health Centre IV, Uganda
2. Walukuba Health Centre IV, Uganda
When is the study starting and how long is it expected to run for?
January 2020 to December 2020 (updated 11/11/2020, previously: January 2021) (updated 14/07/2020, previously: September 2020)
Who is funding the study?
1. ARLA Food for Health, Denmark
2. Danish Dairy Research Foundation, Denmark
3. Nutriset, France
4. University of Copenhagen, Denmark
Who is the main contact?
Prof Henrik Friis
hfr@nexs.ku.dk
Dr Ezekiel Mupere
mupez@yahoo.com
Trial website
Contact information
Type
Scientific
Primary contact
Prof Henrik Friis
ORCID ID
http://orcid.org/0000-0002-2848-2940
Contact details
Rolighedsvej 26
Frederiksberg
1958
Denmark
+45 26253968
hfr@nexs.ku.dk
Type
Scientific
Additional contact
Dr Ezekiel Mupere
ORCID ID
http://orcid.org/0000-0002-8746-9009
Contact details
Paediatrics and Child Health
Makerere University
Kampala
P.O Box 7072
Uganda
+256 776 161 327
mupez@yahoo.com
Additional identifiers
EudraCT number
Nil known
ClinicalTrials.gov number
Nil known
Protocol/serial number
D222
Study information
Scientific title
The role of milk protein and whey permeate in the growth and development of stunted children: a randomised controlled trial in Eastern Uganda
Acronym
MAGNUS
Study hypothesis
1. Milk protein and whey permeate in a lipid-based nutrient supplement (LNS) increases linear growth among children with stunting
2. Milk protein and whey permeate in a LNS increases ponderal growth and fat-free mass accretion, haemoglobin, and child development among children with stunting
3. Supplementation with LNS, with or without milk ingredients, increases linear and ponderal growth, fat-free mass accretion, haemoglobin and child development in children with stunting
4. The effects of milk protein and whey permeate in LNS, or LNS itself, on linear and ponderal growth, fat-free mass accretion, haemoglobin and child development in children with stunting, are mediated by effects on markers of environmental enteric dysfunction
Ethics approval
Approved 20/12/2019, School of Medicine Research and Ethics committee (SOMREC) at Makerere University (PO Box 7072, Kampala, Uganda; +256 414 533541; rresearch9@gmail.com), ref: 2019-013
Study design
Randomized controlled double-blind two-by-two factorial trial
Primary study design
Interventional
Secondary study design
2-by-2 factorial
Trial setting
Community
Trial type
Other
Patient information sheet
Not available in web format, please use the contact details to request a participant information sheet
Condition
Stunting
Intervention
Children in four study arms will receive a lipid-based nutrient supplement (LNS, 100 gram containing 530 kcal per day) with or without whey permeate and milk protein isolate using a 2-by-2 factorial design. The supplements contain similar proportions of energy, protein and carbohydrates. Each formulation contains a mineral and vitamin mix. The minerals provided by the whey permeate are in addition. The supplements have similar appearance, texture, colour and taste. Children in a fifth study arm will not be supplemented, and serve as a reference. Children in all study arms will receive nutrition counselling. The duration of the intervention is 12 weeks.
Groups:
1. LNS with whey permeate and milk protein isolate
2. LNS with whey permeate and without milk protein isolate
3. LNS without whey permeate and with milk protein isolate
4. LNS without whey permeate and without milk protein isolate
5. No supplement
In 2 and 4, milk protein isolate is replaced by soy protein isolate. In 3 and 4, whey permeate is replaced by maltodextrin.
Randomisation will be done stratified by site and using variable block size.
Intervention type
Supplement
Phase
Drug names
Primary outcome measure
Measured at baseline and 12-weeks:
1. Knee-heel length (mm)
2. Height (cm)
Secondary outcome measures
Measured at baseline and 12-weeks:
1. Mid-upper arm circumference (mm)
2. Weight (g)
3. Height-for-age z-scores (HAZ)
4. Weight-for-height z-scores (WHZ)
5. Weight-for-age z-scores (WAZ)
6. Child development index (CDI)
7. Head circumference (cm)
8. Bioimpedance: Fat mass (FM, kg), fat-free mass (FFM, kg), fat mass index (FMI, kg/m2), fat-free mass index (FFMI, kg/m2)
9. Skin folds: triceps, subscapularis (mm)
Blood tests:
10. Haemoglobin (g/L)
11. Serum/plasma insulin-like Growth Factor-1 (IGF-1)
12. Serum/plasma insulin
13. Serum C-reactive protein
14. Serum alpha-1-acid glycoprotein
15. Plasma citrulline
16. Serum ferritin and transferrin receptors (markers of iron status)
17. Plasma cobalamin and methylmalonic acid (markers of B12 status)
18. Plasma folate
19. Serum retinol
Fecal tests:
20. Fecal myeloperoxidase
21. Fecal neopterin
22. Fecal alpha-1-antitrypsin
23. Gut microbiota
24. Morbidity (including diarrhea, pneumonia, fever, malaria), safety (deterioration to MAM or SAM and mortality) measured using patient records
Overall trial start date
01/01/2018
Overall trial end date
18/12/2020
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Age 12 - 59 months
2. Height-age-Z < -2 according to WHO growth standards (2006)
3. Care-taker able and willing to return for follow-up visits and agrees to phone follow-up
4. Living within the catchment area
5. Written informed consent given by parent/caregiver
Participant type
Other
Age group
Child
Gender
Both
Target number of participants
750
Participant exclusion criteria
1. Severe acute malnutrition, defined as MUAC <115 mm OR WHZ<-3 OR bilateral pitting oedema
2. Medical complications requiring hospitalization
3. Obvious disability that impedes eating capacity
4. Disability that makes length/height assessment problematic
5. Participation in another study which impacts on this study or previous enrollment in this study
6. Family plans to move away from the catchment area in the next 6 months
7. History or known allergy to peanuts or milk
Recruitment start date
31/01/2020
Recruitment end date
30/06/2020
Locations
Countries of recruitment
Uganda
Trial participating centre
Buwenge Health Centre IV
Jinja
TBD
Uganda
Trial participating centre
Walukuba Health Centre IV
Jinja
TBD
Uganda
Sponsor information
Organisation
University of Copenhagen
Sponsor details
Nørre Allé 51
Copenhagen
2200
Denmark
+45 3532 0829
hfr@nexs.ku.dk
Sponsor type
University/education
Website
Funders
Funder type
Research organisation
Funder name
ARLA Food for Health, Denmark
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Danish Dairy Research Foundation, Denmark
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Nutriset, France
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
University of Copenhagen, Denmark
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Planned publication in a high-impact peer-reviewed journal.
IPD sharing statement:
The datasets generated during and/or analysed during the current study are not expected to be made available due to legal reasons.
Intention to publish date
31/12/2021
Participant level data
Not expected to be available
Basic results (scientific)
Publication list
Publication citations
Additional files
- ISRCTN13093195_PROTOCOL_V5_03Dec2019.pdf uploaded 11/11/2020