Severe WastingProtein+NCT05737472
High-protein Quantity and Quality RUTF in Improving Linear Growth Among Children With Severe Wasting
A study testing High-protein RUTF and Standard RUTF in people with Severe Wasting and Severe Acute Malnutrition, run by The Hospital for Sick Children at 1 site in Malawi.
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. Read more about this study
- Who is it for?
- Ages 6 to 23 months
- Conditions the study is for
- Severe Wasting, Severe Acute Malnutrition
- What is being tested?
- High-protein RUTF and Standard RUTF
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 128 participants
- Where
- 1 siteMalawi
- Study dates
- 14 Nov 2022to 23 Aug 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 23 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Malawi1 site
Ndirande, Mbayani, Bangwe, Limbe and Bangwe health centres
Blantyre, 000
About this study
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
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.
Read the 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.
- Conditions
- Severe Wasting, Severe Acute Malnutrition
- Being tested
- High-protein RUTF, Standard RUTF
- Keywords
- Child health, Ready-to-use therapeutic food, Severe acute malnutrition, RUTF, SAM, Wasting, Outpatient Therapeutic Programme, OTP
- Medical subject headings
- Cachexia, Severe Acute Malnutrition
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High-protein RUTFDietary supplement
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 RUTFDietary supplement
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.
| Study group | Role | What they receive |
|---|---|---|
| Standard RUTF | Active comparator | 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. Receives: Dietary Supplement: Standard RUTF |
| High-protein RUTF | Experimental | 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. Receives: Dietary Supplement: High-protein RUTF |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 4 weeks
Secondary outcomes (13)
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.
Measured: 8 weeks
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
Measured: 8 weeks
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
Measured: 8 weeks
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
Measured: 8 weeks
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
Measured: 4 weeks
Changes in IGFBP3
To assess the efficacy of high-protein-RUTF with higher protein quality and quantity compared to standard RUTF in increasing IGFFBP3
Measured: 4 weeks
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
Measured: 8 weeks
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
Measured: 8 weeks
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
Measured: 4
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
Measured: 4
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
Measured: 4
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)
Measured: 8 weeks
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)
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2023
- Study start14 Nov 2022
- Primary completion26 Jul 2023
- Study completion23 Aug 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Severe WastingStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 128 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Hospital for Sick Children
- Sponsor type
- University, hospital or other
- Collaborators
- Ministry of Health, Malawi, Schlumberger Foundation, Nutriset, Friends of Sick Children, Malawi
- Responsible party
- Principal investigator, Robert Bandsma, The Hospital for Sick Children
- Investigators
- Isabel Potani, PhD(c), Principal investigator, The Hospital for Sick Children
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05737472
- Sponsor's protocol ID
- 1000079230
- Acronym
- Protein+
- Status last verified
- Apr 2024
- First submitted
- 21 Dec 2022
- Last updated
- 30 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: De-identified data may be made available after publication of the results in line with the study's sponsor's procedures for release.
Publications
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.
PubMed 33838044Shivakumar 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.
PubMed 31724705Potani I, Daniel AI, Briend A, Courtney-Martin G, Berkley JA, Voskuijl W, Vresk L, Bourdon C, Kathumba S, Mbale E, Bandsma RHJ. A protocol for a proof-of-concept randomized control trial testing increased protein quantity and quality in ready-to-use therapeutic food in improving linear growth among 6-23-month-old children with severe wasting in Malawi. PLoS One. 2023 Aug 24;18(8):e0287680. doi: 10.1371/journal.pone.0287680. eCollection 2023.
PubMed 37619218
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05737472
- Acronym / sponsor ID
- Protein+ / 1000079230
- Conditions
- Severe Wasting, Severe Acute Malnutrition
- Keywords
- Child health, Ready-to-use therapeutic food, Severe acute malnutrition, RUTF, SAM, Wasting, Outpatient Therapeutic Programme, OTP
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 128 participants (actual)
- Lead sponsor
- The Hospital for Sick ChildrenUniversity, hospital or other
- Collaborators
- Ministry of Health, Malawi, Schlumberger Foundation, Nutriset, Friends of Sick Children, Malawi
- Study start
- 14 Nov 2022 (actual)
- Primary completion
- 26 Jul 2023 (actual)
- Study completion
- 23 Aug 2023 (actual)
- First posted
- 21 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard RUTF | Active comparator | Dietary Supplement: Standard RUTFThe 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. |
| High-protein RUTF | Experimental | Dietary Supplement: High-protein RUTFThe 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. |
Who may qualify
- Ages
- 6 to 23 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| High-protein RUTFThe 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 | Dietary supplement | High-protein RUTF |
| Standard RUTFThe 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. | Dietary supplement | Standard RUTF |
Primary outcome
Changes in plasma IGF-1
Time frame: 4 weeks
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.
13 secondary outcomes
Changes in height for age z score
Time frame: 8 weeks
Changes in weight for age z score
Time frame: 8 weeks
Changes in weight for height z score
Time frame: 8 weeks
Changes in knee heel length
Time frame: 8 weeks
Changes in plasma essential amino acid profile leucine, threonine and tryptophan
Time frame: 4 weeks
Changes in IGFBP3
Time frame: 4 weeks
Changes in fat free mass accretion
Time frame: 8 weeks
Changes in fat mass accretion
Time frame: 8 weeks
Acceptability of high-protein RUTF
Time frame: 4
Acceptability of high-protein RUTF
Time frame: 4
Compliance of high-protein RUTF
Time frame: 4
Safety of the high protein RUTF formulation:adverse events
Time frame: 8 weeks
Safety of the high protein RUTF formulation: severe adverse events
Time frame: 8 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2024.
- Background: PubMed 33838044Potani 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.
- Background: PubMed 31724705Shivakumar 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.
- Derived from this study: PubMed 37619218Potani I, Daniel AI, Briend A, Courtney-Martin G, Berkley JA, Voskuijl W, Vresk L, Bourdon C, Kathumba S, Mbale E, Bandsma RHJ. A protocol for a proof-of-concept randomized control trial testing increased protein quantity and quality in ready-to-use therapeutic food in improving linear growth among 6-23-month-old children with severe wasting in Malawi. PLoS One. 2023 Aug 24;18(8):e0287680. doi: 10.1371/journal.pone.0287680. eCollection 2023.
- Individual participant dataSharing planned: No. De-identified data may be made available after publication of the results in line with the study's sponsor's procedures for release.
Related trials for Severe Wasting
Recruiting
Milk Fat Globule Membrane-Enhanced RUTF for Children With Severe Acute Malnutrition
Severe Acute Malnutrition, Cognitive Impairment
Recruiting
Increasing the Coverage of Severe Acute Malnutrition (SAM) Treatment in Ethiopia
Acute Malnutrition, Severe, Malnutrition, Child
Active, not recruiting
Choline to Improve Malnutrition and Enhance Cognition
Severe Acute Malnutrition, Cognitive Impairment
Active, not recruiting
Regular Growth Monitoring (RGM) of Young Children in Guinea-Bissau
Severe Acute Malnutrition, Moderate Acute Malnutrition (MAM)
Recruiting
Expanding Coverage of Severe Acute Malnutrition (SAM) Treatment in Kenya
Acute Malnutrition, Severe, Malnutrition, Child
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Isabel Potani, PhD(c) principal investigator
The Hospital for Sick Children
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing High-protein RUTF and Standard RUTF in people with Severe Wasting and Severe Acute Malnutrition, run by The Hospital for Sick Children at 1 site in Malawi.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Malawi. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in plasma IGF-1 (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05737472, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Apr 2024.