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
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
Scientific
Rolighedsvej 26
Frederiksberg
1958
Denmark
 ORCID ID |
0000-0002-2848-2940 |
|---|---|
| Phone | +45 26253968 |
| hfr@nexs.ku.dk |
Scientific
Paediatrics and Child Health
Makerere University
Kampala
P.O Box 7072
Uganda
| ORCID ID |
0000-0002-8746-9009 |
|---|---|
| Phone | +256 776 161 327 |
| mupez@yahoo.com |
Study information
| Study design | Randomized controlled double-blind two-by-two factorial trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | 2-by-2 factorial |
| Study setting(s) | Community |
| Study type | Other |
| Participant information sheet | Not available in web format, please use the contact details to request a 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 | 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 study start date | 01/01/2018 |
| Completion date | 18/12/2020 |
Eligibility
| Participant type(s) | Other |
|---|---|
| Age group | Child |
| Lower age limit | 12 Months |
| Upper age limit | 59 Months |
| Sex | Both |
| Target number of participants | 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
TBD
Uganda
TBD
Uganda
Sponsor information
University/education
Nørre Allé 51
Copenhagen
2200
Denmark
| Phone | +45 3532 0829 |
|---|---|
| hfr@nexs.ku.dk | |
| Website | https://nexs.ku.dk/english/ |
"ROR" |
https://ror.org/035b05819 |
Funders
Funder type
Research organisation
No information available
No information available
No information available
No information available
Results and Publications
| Intention to publish date | 31/12/2022 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal. |
| 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? |
|---|---|---|---|---|---|
| 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
