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

Primary Purpose

Severe Wasting, Severe Acute Malnutrition

Status
Recruiting
Phase
Not Applicable
Locations
Malawi
Study Type
Interventional
Intervention
High-protein RUTF
Standard RUTF
Sponsored by
The Hospital for Sick Children
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Severe Wasting focused on measuring Child health, Ready-to-use therapeutic food, Severe acute malnutrition, RUTF, SAM, Wasting, Outpatient Therapeutic Programme, OTP

Eligibility Criteria

6 Months - 23 Months (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Ndirande, Mbayani, Bangwe, Limbe and Bangwe health centresRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Standard RUTF

High-protein RUTF

Arm Description

The standard RUTF dose is according to weight as per the WHO 2013 guideline, thus 150-220Kcal/kg/day. A child will receive a weekly ration for 8 consecutive weeks from enrolment.

The high-protein RUTF dose is according to weight as per the WHO 2013 guideline, thus 150-220Kcal/kg/day. A child will receive a weekly ration for 8 consecutive weeks from enrolment.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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
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
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
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
Changes in IGFBP3
To assess the efficacy of high-protein-RUTF with higher protein quality and quantity compared to standard RUTF in increasing IGFFBP3
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
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
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
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
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
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)
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)

Full Information

First Posted
December 21, 2022
Last Updated
February 10, 2023
Sponsor
The Hospital for Sick Children
Collaborators
Ministry of Health, Malawi, Schlumberger Foundation, Nutriset, Friends of Sick Children, Malawi
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1. Study Identification

Unique Protocol Identification Number
NCT05737472
Brief Title
High-protein Quantity and Quality RUTF in Improving Linear Growth Among Children With Severe Wasting
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 14, 2022 (Actual)
Primary Completion Date
June 14, 2023 (Anticipated)
Study Completion Date
July 14, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The Hospital for Sick Children
Collaborators
Ministry of Health, Malawi, Schlumberger Foundation, Nutriset, Friends of Sick Children, Malawi

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Severe Wasting, Severe Acute Malnutrition
Keywords
Child health, Ready-to-use therapeutic food, Severe acute malnutrition, RUTF, SAM, Wasting, Outpatient Therapeutic Programme, OTP

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
The patients, investigators, care providers, and data analysts will be blinded from the treatment allocation until data analysis is complete, thus quadruple blinding. The two RUTFs will be packaged in identical 92g sachets. The RUTFs will be as similar as possible in colour, texture, and smell. The two packages/sachets of the two types of RUTF will differ by colour, and the number code will be either grey-88 or purple-99 (the colour code will be unique to each RUTF type). An independent statistician will perform the colour allocation.
Allocation
Randomized
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Standard RUTF
Arm Type
Active Comparator
Arm Description
The standard RUTF dose is according to weight as per the WHO 2013 guideline, thus 150-220Kcal/kg/day. A child will receive a weekly ration for 8 consecutive weeks from enrolment.
Arm Title
High-protein RUTF
Arm Type
Experimental
Arm Description
The high-protein RUTF dose is according to weight as per the WHO 2013 guideline, thus 150-220Kcal/kg/day. A child will receive a weekly ration for 8 consecutive weeks from enrolment.
Intervention Type
Dietary Supplement
Intervention Name(s)
High-protein RUTF
Intervention Description
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
Intervention Type
Dietary Supplement
Intervention Name(s)
Standard RUTF
Intervention Description
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.
Primary Outcome Measure Information:
Title
Changes in plasma IGF-1
Description
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.
Time Frame
4 weeks
Secondary Outcome Measure Information:
Title
Changes in height for age z score
Description
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.
Time Frame
8 weeks
Title
Changes in weight for age z score
Description
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
Time Frame
8 weeks
Title
Changes in weight for height z score
Description
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
Time Frame
8 weeks
Title
Changes in knee heel length
Description
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
Time Frame
8 weeks
Title
Changes in plasma essential amino acid profile leucine, threonine and tryptophan
Description
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
Time Frame
4 weeks
Title
Changes in IGFBP3
Description
To assess the efficacy of high-protein-RUTF with higher protein quality and quantity compared to standard RUTF in increasing IGFFBP3
Time Frame
4 weeks
Title
Changes in fat free mass accretion
Description
• 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
Time Frame
8 weeks
Title
Changes in fat mass accretion
Description
• 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
Time Frame
8 weeks
Title
Acceptability of high-protein RUTF
Description
• 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
Time Frame
4
Title
Acceptability of high-protein RUTF
Description
• 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
Time Frame
4
Title
Compliance of high-protein RUTF
Description
• 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
Time Frame
4
Title
Safety of the high protein RUTF formulation:adverse events
Description
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)
Time Frame
8 weeks
Title
Safety of the high protein RUTF formulation: severe adverse events
Description
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)
Time Frame
8 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Months
Maximum Age & Unit of Time
23 Months
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Isabel Potani, PhD(c)
Phone
+41779119432
Email
isabelpotani@mail.utoronto.ca
First Name & Middle Initial & Last Name or Official Title & Degree
Robert Bandsma, PhD
Email
robert.bandsma@sickkids.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Isabel Potani, PhD(c)
Organizational Affiliation
The Hospital for Sick Children
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ndirande, Mbayani, Bangwe, Limbe and Bangwe health centres
City
Blantyre
State/Province
Please Select
ZIP/Postal Code
000
Country
Malawi
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Agness Malamula, BScN
Phone
+265999209481
Email
agnesmalamula@gmail.com
First Name & Middle Initial & Last Name & Degree
Isabel Potani
First Name & Middle Initial & Last Name & Degree
Allison Daniel
First Name & Middle Initial & Last Name & Degree
James .A. Berkley
First Name & Middle Initial & Last Name & Degree
Wieger Voskjuil
First Name & Middle Initial & Last Name & Degree
Glenda Courtney Martin
First Name & Middle Initial & Last Name & Degree
Laura Vresk
First Name & Middle Initial & Last Name & Degree
Sylvester Kathumba
First Name & Middle Initial & Last Name & Degree
Agness Malamula
First Name & Middle Initial & Last Name & Degree
Falth Kalyolyo
First Name & Middle Initial & Last Name & Degree
Takondwa Mbulaje
First Name & Middle Initial & Last Name & Degree
Robert Bandsma
First Name & Middle Initial & Last Name & Degree
Andre Briend

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
De-identified data may be made available after publication of the results in line with the study's sponsor's procedures for release.
Citations:
PubMed Identifier
33838044
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.
Results Reference
background
PubMed Identifier
31724705
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.
Results Reference
background

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

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