High-protein Quantity and Quality RUTF in Improving Linear Growth Among Children With Severe Wasting

Severe Acute Malnutrition Clinical Trial

— Protein+  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05737472
• Other study ID #: 1000079230
• Status: Completed
• Phase: N/A
• Start date: November 14, 2022
• Est. completion date: August 23, 2023

Study information

• Verified date: April 2024
• Source: The Hospital for Sick Children
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 128
• Est. completion date: August 23, 2023
• Est. primary completion date: July 26, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 23 Months

Eligibility

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

Related Conditions & MeSH terms

• Cachexia
• Malnutrition
• Severe Acute Malnutrition
• Severe Wasting

Intervention

Dietary Supplement:
• High-protein RUTF
The high-protein RUTF is isocaloric to the standard RUTF. To have a higher protein quantity and quality, the recipe has greater proportions of milk powder plus whey protein and vegetable oil. A total of 15% of energy is from protein. The protein quality score, digestible indispensable amino acid score (DIAAS )of the high protein, RUTF is 1.18 which is equivalent to a Protein Digestibility Corrected Amino Acid Score (PDCAAS) of 1.19
• Standard RUTF
The standard RUTF was manufactured according to WHO recommendations, with at least 50% of protein-sourced dairy, mainly skim milk. A total of 10% of energy is from protein. The protein quality score, digestible indispensable amino acid score (DIAAS) of the standard RUTF is 0.76, which is equivalent to a Protein Digestibility Corrected Amino Acid Score (PDCAAS) of 0.86.

Locations

Country	Name	City	State
Malawi	Ndirande, Mbayani, Bangwe, Limbe and Bangwe health centres	Blantyre

Sponsors (5)

Lead Sponsor	Collaborator
The Hospital for Sick Children	Friends of Sick Children, Malawi, Ministry of Health, Malawi, Nutriset, Schlumberger Foundation

Country where clinical trial is conducted

Malawi, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in plasma IGF-1	To assess the efficacy of high-protein-RUTF with higher protein quality and quantity compared to standard RUTF in increasing circulating IGF- 1 in 6-23-month-old children with severe wasting.	4 weeks
Secondary	Changes in height for age z score	To assess the efficacy of high-protein-RUTF with higher protein quality and quantity compared to standard RUTF in improving change in height-for-age z score.	8 weeks
Secondary	Changes in weight for age z score	To assess the efficacy of high-protein-RUTF with higher protein quality and quantity compared to standard RUTF in improving change in weight for age z score	8 weeks
Secondary	Changes in weight for height z score	To assess the efficacy of high-protein-RUTF with higher protein quality and quantity compared to standard RUTF in improving change in weight for height z score	8 weeks
Secondary	Changes in knee heel length	To assess the efficacy of high-protein-RUTF with higher protein quality and quantity compared to standard RUTF in improving change in knee heel length	8 weeks
Secondary	Changes in plasma essential amino acid profile leucine, threonine and tryptophan	To assess the efficacy of high-protein-RUTF with higher protein quality and quantity compared to standard RUTF in improving plasma essential amino acids: leucine, threonine and tryptophan	4 weeks
Secondary	Changes in IGFBP3	To assess the efficacy of high-protein-RUTF with higher protein quality and quantity compared to standard RUTF in increasing IGFFBP3	4 weeks
Secondary	Changes in fat free mass accretion	• To assess the efficacy of high-protein-RUTF with higher protein quality and quantity compared to standard RUTF in improving fat free mass accretions (kg/m2) using bioelectrical impedance and skinfold thickness	8 weeks
Secondary	Changes in fat mass accretion	• To assess the efficacy of high-protein-RUTF with higher protein quality and quantity compared to standard RUTF in improving fat mass accretion (kg/m2) using bio-electrical impedance assessment and skinfold thickness	8 weeks
Secondary	Acceptability of high-protein RUTF	• To assess acceptability of the high protein RUTF formulation compared to standard RUTF among children with severe wasting using an adaptation of action against hunger RUTF apettite test	4
Secondary	Acceptability of high-protein RUTF	• To assess acceptability of the high protein RUTF formulation compared to standard RUTF among children with severe wasting by observing RUTF intake at participant homes for 5 hours at a single time point	4
Secondary	Compliance of high-protein RUTF	• To assess compliance of the high protein RUTF formulation compared to standard RUTF among children with severe wasting by conducting in-depth interviews with the caregivers	4
Secondary	Safety of the high protein RUTF formulation:adverse events	To assess the safety of high-protein-RUTF compared to standard RUTF by recording adverse events (defined as any untoward event including morbidity reported by the participant or detected by the investigator)	8 weeks
Secondary	Safety of the high protein RUTF formulation: severe adverse events	To assess the safety of high-protein-RUTF compared to standard RUTF by recording adverse events (defined as any life threatening event reported by the participant or detected by the investigator)	8 weeks