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
Secondary identifying numbers D222
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 logoORCID 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 logoORCID ID 0000-0002-8746-9009
Phone +256 776 161 327
Email mupez@yahoo.com

Study information

Study designRandomized controlled double-blind two-by-two factorial trial
Primary study designInterventional
Secondary study design2-by-2 factorial
Study setting(s)Community
Study typeOther
Participant information sheet Not available in web format, please use the contact details to request a participant information sheet
Scientific titleThe role of milk protein and whey permeate in the growth and development of stunted children: a randomised controlled trial in Eastern Uganda
Study acronymMAGNUS
Study objectives1. 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) studiedStunting
InterventionChildren 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 typeSupplement
Primary outcome measureMeasured at baseline and 12-weeks:
1. Knee-heel length (mm)
2. Height (cm)
Secondary outcome measuresMeasured 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 study start date01/01/2018
Completion date18/12/2020

Eligibility

Participant type(s)Other
Age groupChild
Lower age limit12 Months
Upper age limit59 Months
SexBoth
Target number of participants750
Total final enrolment750
Key inclusion criteria1. 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 criteria1. 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 enrolment31/01/2020
Date of final enrolment30/06/2020

Locations

Countries of recruitment

  • Uganda

Study participating centres

Buwenge Health Centre IV
Jinja
TBD
Uganda
Walukuba Health Centre IV
Jinja
TBD
Uganda

Sponsor information

University of Copenhagen
University/education

Nørre Allé 51
Copenhagen
2200
Denmark

Phone +45 3532 0829
Email hfr@nexs.ku.dk
Website https://nexs.ku.dk/english/
ROR logo "ROR" https://ror.org/035b05819

Funders

Funder type

Research organisation

ARLA Food for Health, Denmark

No information available

Danish Dairy Research Foundation, Denmark

No information available

Nutriset, France

No information available

University of Copenhagen, Denmark

No information available

Results and Publications

Intention to publish date31/12/2022
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot expected to be made available
Publication and dissemination planPlanned publication in a high-impact peer-reviewed journal.
IPD sharing planThe 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?
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
Protocol article 24/04/2021 13/08/2021 Yes No
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
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

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