Clinical trial NCT05737472: High-protein Quantity and Quality RUTF in Improving Linear Growth Among Children With Severe Wasting
Official title: A Proof-of-concept Randomized Control Trial on the Role of Higher Protein Quantity and Quality-ready-to-use Therapeutic Food in Improving Linear Growth Among 6-23-month-old Children With Severe Wasting
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Severe Wasting
Severe Acute Malnutrition
Keywords: Child health
Ready-to-use therapeutic food
Severe acute malnutrition
RUTF
SAM
Wasting
Outpatient Therapeutic Programme
OTP
Lead sponsor: The Hospital for Sick Children
Sponsor class: OTHER
Collaborators: name: Ministry of Health, Malawi
name: Schlumberger Foundation
name: Nutriset
name: Friends of Sick Children, Malawi
First posted: 2023-02-21
Enrollment: 128
Sex: ALL
Minimum age (years): 6
Maximum age (years): 23
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a proof-of-concept trial that aims to compare the efficacy of an 8-week treatment with higher-protein-Ready-to-Use Therapeutic Foods (RUTF) with standard RUTF in improving levels of markers of growths, height, nutritional recovery, and lean mass deposition among children with severe wasting. The study will also assess the safety and acceptability of the high-protein RUTF in comparison to the standard RUTF. The study will be conducted at four outpatient therapeutic programs in the Blantyre district of Malawi.

Detailed description: RUTF has successfully promoted recovery from severe wasting and widened treatment coverage. However, RUTF does not sufficiently promote linear growth, leaving many survivors of severe wasting at risk of persistent stunting. Stunting is associated with long-term effects like poor child development and an increased risk of non-communicable diseases in adults. High protein quantity and quality are known to stimulate linear growth; however, an RUTF with a higher protein quantity and quality than the standard RUTF has yet to be tested. The investigators hypothesize that the suboptimal linear growth in children surviving severe malnutrition can be improved by increasing the protein quantity and quality in the standard RUTF formulation. The investigators have designed a high protein quantity and quality RUTF that will be tested in a proof-of-concept quadruple-blind randomised controlled trial study design. The trial aims to compare the efficacy of higher-protein-RUTF and standard RUTF in improving markers of linear growth among 6-23 months old children with severe wasting.

Children aged 6-23 months newly enrolled in outpatient treatment programs for severe wasting and without medical complications are eligible. They will be assigned to either increased protein RUTF or standard RUTF for eight weeks.

The primary outcome is a change in insulin-like growth factor-1 (IGF- 1) after four weeks of treatment. IGF-1 is a hormone that is mechanistically linked with growth. Secondary outcomes include ponderal and linear growth changes from baseline measured at eight weeks and plasma amino acid profile at four weeks. Other secondary outcomes are the acceptability and safety of high protein RUTF compared to standard RUTF. These findings will help to determine the optimal protein composition of RUTF to promote linear growth when treating severe wasting in children.

Eligibility criteria: Inclusion Criteria:

* Infants 6-23 months of age with severe wasting at OTP admission according to the WHO criteria: WHZ below -3 or MUAC below 115mm.
* Parent or guardian is able and available to consent
* Children who are able to feed orally in the usual state of health
* The primary caregiver plans to stay in the study area during the duration of the study.

Exclusion Criteria:

* Children with medical complications as per the CMAM guidelines (lack of appetite, severe oedematous malnutrition, acute infections)
* mild and moderate nutritional oedema
* Children with a known terminal illness (e.g. cancer), cerebral palsy (CP), tuberculosis (TB,) HIV infected or exposed
* Children who had SAM in the last 8 weeks, i.e., SAM relapses in the last 8 weeks
* Children admitted to any NRU due to complicated SAM in the previous 4 weeks will also be excluded
* Children whose caregivers refuse to give consent or whose primary givers are not available to give consent
* Children who were previously enrolled in this trial or currently enrolled in this trial whose sibling has also been enrolled in the study
* Children with known intolerance or allergy to high protein diets will be excluded as well as known intolerance or allergy to milk/lactose

Primary outcomes:
measure: Changes in plasma IGF-1
timeFrame: 4 weeks
Secondary outcomes:
measure: Changes in height for age z score
timeFrame: 8 weeks
measure: Changes in weight for age z score
timeFrame: 8 weeks
measure: Changes in weight for height z score
timeFrame: 8 weeks
measure: Changes in knee heel length
timeFrame: 8 weeks
measure: Changes in plasma essential amino acid profile leucine, threonine and tryptophan
timeFrame: 4 weeks
measure: Changes in IGFBP3
timeFrame: 4 weeks
measure: Changes in fat free mass accretion
timeFrame: 8 weeks
measure: Changes in fat mass accretion
timeFrame: 8 weeks
measure: Acceptability of high-protein RUTF
timeFrame: 4
measure: Acceptability of high-protein RUTF
timeFrame: 4
measure: Compliance of high-protein RUTF
timeFrame: 4
measure: Safety of the high protein RUTF formulation:adverse events
timeFrame: 8 weeks
measure: Safety of the high protein RUTF formulation: severe adverse events
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Blantyre
country: Malawi
facility: Ndirande, Mbayani, Bangwe, Limbe and Bangwe health centres
Study officials:
affiliation: The Hospital for Sick Children
name: Isabel Potani, PhD(c)
role: PRINCIPAL_INVESTIGATOR
References:
citation: Potani I, Spiegel-Feld C, Brixi G, Bendabenda J, Siegfried N, Bandsma RHJ, Briend A, Daniel AI. Ready-to-Use Therapeutic Food (RUTF) Containing Low or No Dairy Compared to Standard RUTF for Children with Severe Acute Malnutrition: A Systematic Review and Meta-Analysis. Adv Nutr. 2021 Oct 1;12(5):1930-1943. doi: 10.1093/advances/nmab027.
citation: Shivakumar N, Jackson AA, Courtney-Martin G, Elango R, Ghosh S, Hodgkinson S, Xipsiti M, Lee WTK, Kurpad AV, Tome D. Protein Quality Assessment of Follow-up Formula for Young Children and Ready-to-Use Therapeutic Foods: Recommendations by the FAO Expert Working Group in 2017. J Nutr. 2020 Feb 1;150(2):195-201. doi: 10.1093/jn/nxz250.