The role of milk protein and other dried milk products in the growth and development of stunted children

ISRCTN	ISRCTN13093195
DOI	https://doi.org/10.1186/ISRCTN13093195
ClinicalTrials.gov (NCT)	Nil known
Clinical Trials Information System (CTIS)	Nil known
Protocol serial number	D222
Sponsor	University of Copenhagen
Funders	ARLA Food for Health, Denmark, Danish Dairy Research Foundation, Denmark, Nutriset, France, University of Copenhagen, Denmark

Submission date: 06/01/2020
Registration date: 13/01/2020
Last edited: 09/08/2024

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nutritional, Metabolic, Endocrine

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

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

Contact information

Prof Henrik Friis
Scientific

Rolighedsvej 26
Frederiksberg
1958
Denmark

ORCID ID	0000-0002-2848-2940
Phone	+45 26253968
Email	hfr@nexs.ku.dk

Dr Ezekiel Mupere
Scientific

Paediatrics and Child Health
Makerere University
Kampala
P.O Box 7072
Uganda

ORCID ID	0000-0002-8746-9009
Phone	+256 776 161 327
Email	mupez@yahoo.com

Study information

Primary study design	Interventional
Study design	Randomized controlled double-blind two-by-two factorial trial
Secondary study design	2-by-2 factorial
Study type	Participant information sheet
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
Study acronym	MAGNUS
Study objectives	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(s)	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
Health condition(s) or problem(s) studied	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
Primary outcome measure(s)	Measured at baseline and 12-weeks: 1. Knee-heel length (mm) 2. Height (cm)
Key secondary outcome measure(s)	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
Completion date	18/12/2020

Eligibility

Participant type(s)	Other
Age group	Child
Lower age limit	12 Months
Upper age limit	59 Months
Sex	All
Target sample size at registration	750
Total final enrolment	750
Key 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
Key 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
Date of first enrolment	31/01/2020
Date of final enrolment	30/06/2020

Locations

Countries of recruitment

Uganda

Study participating centres

Buwenge Health Centre IV

Jinja
TBD
Uganda

Walukuba Health Centre IV

Jinja
TBD
Uganda

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not expected to be made available
IPD sharing plan	The datasets generated during and/or analysed during the current study are not expected to be made available due to legal reasons.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	23/05/2023	24/05/2023	Yes	No
Results article	Analysis of plasma citrulline levels and correlations	20/12/2023	27/12/2023	Yes	No
Protocol article		24/04/2021	13/08/2021	Yes	No
Other publications	Secondary analysis	24/01/2024	29/01/2024	Yes	No
Other publications	Correlates of body composition using baseline measurements data	05/08/2024	09/08/2024	Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Protocol file	version V5	03/12/2019	11/11/2020	No	No
Statistical Analysis Plan	version 01	16/04/2021	19/04/2021	No	No

Additional files

ISRCTN13093195_PROTOCOL_V5_03Dec2019.pdf: uploaded 11/11/2020
ISRCTN13093195_SAP_V01_16Apr2021.pdf: uploaded 19/04/2021

Editorial Notes

09/08/2024: Publication reference added.
29/01/2024: Publication reference added.
27/12/2023: Publication reference added.
24/05/2023: Publication reference added.
20/12/2021: The following changes were made to the trial record:
1. The total final enrolment was added.
2. The intention to publish date was changed from 31/12/2021 to 31/12/2022.
13/08/2021: Internal review.
25/05/2021: Publication reference added.
19/04/2021: The statistical analysis plan was uploaded as an additional file.
11/11/2020: The following changes were made to the trial record:
1. Uploaded protocol (not peer reviewed) Version 5, 3 December 2019
2. The overall end date was changed from 30/01/2021 to 18/12/2020.
3. The plain English summary was updated to reflect these changes.
14/07/2020: The following changes were made to the trial record:
1. The overall end date was changed from 30/09/2020 to 30/01/2021.
2. The plain English summary was updated to reflect these changes.
09/01/2020: Trial’s existence confirmed by School of Medicine Research and Ethics committee (SOMREC) at Makerere University