Condition category
Nutritional, Metabolic, Endocrine
Date applied
06/01/2020
Date assigned
13/01/2020
Last edited
14/07/2020
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
No longer recruiting

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 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

30/10/2021

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

https://nexs.ku.dk/english/

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

Editorial Notes

14/07/2020: The following changes were made to the trial record: 1. The overall end date was changed from 30/09/2020 to 30/10/2021. 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