Slow Introduction of Nutrition for Ill Malnourished Children

NCT06846749 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: 1000081371
• Study Type: interventional
• Target: 135
• Locations: 2 countries
• Sites: 2

Brief Summary

The goal of this clinical trial is to learn if giving lower calorie feeds during the first stage of treatment helps improve survival in severely malnourished children who are ill. The main question it aims to answer is: Is it safe to feed ill severely malnourished children lower calorie feeds during the early treatment phase? Researchers will compare two lower calorie feeds (F50 and F35) to the standard feed (F75) to see if they help children recover safely without increasing their risk of low blood sugar (hypoglycemia). Participants will:

• Receive one of the lower calorie feeds (F50 or F35) or the standard feed (F75) during their hospital stay.
• Be closely monitored for low blood sugar and signs for worsening of clinical symptoms.
• Be treated until they are stable and ready to be fed more calories to help them gain weight.

Conditions

Malnutrition, Severe Acute; Malnutrition, Child; Malnutrition, Infant

Keywords

Overfeeding, Refeeding syndrome, Glucose Dysregulation

Outcome Measures

Primary Outcomes (1)

• Episodes of moderate hypoglycemia

  The occurrence of at least one episode of moderate hypoglycemia (less than or equal to 3.0 mmol/l) during the stabilization phase as measured utilizing the Dexcom Continous Glucose Monitoring Device and/or bed-side glucometer (OneTouch).

  During the period of F75/F50/F35 provision meaning the stabilization phase which is on average 3 days

Secondary Outcomes (12)

• Serious Adverse Events

  During the period of F75/F50/F35 provision meaning the stabilization phase, which is on average 3 days

• Episodes of hypoglycemia or hyperglycemia

  During the period of F75/F50/F35 provision meaning the stabilization phase, which is on average 3 days

• Duration of the stabilization phase

  The duration of the stabilization phase which is expected to be on average 3 days following enrolment.

• Failed transition to ready-to-use-therapeutic foods (RUTF).

  Transition phase expected to be on average 3 days following start of RUTF

• Duration of hospital stay

  Study enrolment to discharge, which is on average 7 days

Other Outcomes (4)

• Glucose response

  The duration of the stabilization phase, which is on average 3 days

• C-reactive protein and white blood cell count and differential

  Enrolment

• Venous blood gas, lactate, electrolytes

  Day 3 of admission

Study Arms (3)

F75 milk feeds

ACTIVE COMPARATOR

F-75 nutritional stabilization feed was designed in the 1990s assuming that severely malnourished children with infections are metabolically vulnerable and have a range of micronutrient disturbances. F75 aims to provide 95 kcal/kg/day and was intended to support children through early stabilization when fighting infections and not aimed at weight gain. Once clinically stabilized, on average after 3-5 days, children are transitioned from F75 to ready-to-use therapeutic foods (RUTF) that provide substantially higher amount of protein and calories to promote rapid weight gain.

Dietary Supplement: F75 milk feeds

F50 milk feeds

EXPERIMENTAL

The F50 feed has been meticulously formulated by Nutriset. The composition is identical to that of F75, with the only distinction being the reduction in calorie content with F50 aiming to provide 63kcal/kg/day. This ensures that the nutritional parameters and essential components remain consistent, while the lower calorie count aligns with the specific requirements of this trial. Once clinically stabilized, on average after 3-5 days, children are transitioned from F50 to RUTF that provide substantially higher amounts of protein and calories to promote rapid weight gain.

Dietary Supplement: F50 milk feeds

F35 milk feeds

EXPERIMENTAL

The F35 feed has been meticulously formulated by Nutriset. Their composition is identical to that of F75, with the only distinction being the reduction in calorie content with F35 aiming to provide 47kcal/kg/day. This ensures that the nutritional parameters and essential components remain consistent, while the lower calorie count aligns with the specific requirements of this trial. Once clinically stabilized, on average after 3-5 days, children are transitioned from F35 to RUTF that provide substantially higher amounts of protein and calories to promote rapid weight gain.

Dietary Supplement: F35 milk feeds

Interventions

F75 milk feeds DIETARY_SUPPLEMENT

Standard 'F75' (75 kcal/100 ml) 95 kcal/kg/day 12.05 mg/kg/min glucose

Also known as: Therapeutic Milk

F75 milk feeds

F50 milk feeds DIETARY_SUPPLEMENT

Reduced caloric 'F50' (50kcal/100ml) 63 kcal/kg/day 8.03mg/kg/min glucose

Also known as: Therapeutic Milk

F50 milk feeds

F35 milk feeds DIETARY_SUPPLEMENT

Reduced caloric 'F35' (35 kcal/100ml) * 47 kcal/kg/day * 5.62 mg/kg/min glucose

Also known as: Therapeutic Milk

F35 milk feeds

Eligibility Criteria

• Age: 6 Months - 59 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age - greater than or equal to 6 months to less than 59 months (age range for which WHO guidelines were developed and where children are not expected to be exclusively breastfeeding
• Admitted to hospital with acute, non-traumatic illness and having received a maximum of 2 feeds of F75 at time of enrolment
• Severe malnutrition (WHZ \<-3 z-scores of the median WHO growth standards and/or MUAC \<115mm)
• Accompanied by care provider able to provide written or witnessed informed consent
• Primary caregiver plans to stay in the study area for the duration of the study
• Having no more than one clinical sign displayed below "Clinical/Lab Feature \& Criteria"

You may not qualify if:

• Has oedematous malnutrition (excluded for this safety focused trial as fluid accumulation influences weight which is used to calculate required caloric intake)
• Requires immediate cardiac/respiratory resuscitation (chest compressions/ventilation)
• Clinical contraindications for enteral nutrition
• Admission for traumatic or surgical indication
• Weighs \<3.5kg
• Presence of terminal illness likely to result in death within 6 months
• Known congenital heart disease
• Have had 2 documented hypoglycaemic events in hospital
• More than one clinical sign displayed below "Clinical/Lab Feature \& Criteria"
• Primary caregiver declines to provide informed consent
• Clinical/Lab Feature \& Criteria Guidelines
• Clinical/Lab Feature: Respiratory distress Oxygenation Criteria: "Subcostal in-drawing" or "nasal flaring" or "head-nodding"
• Clinical/Lab Feature: Oxygenation Criteria: "Central cyanosis" or SaO2 \<90%
• Clinical/Lab Feature: Circulation Criteria: Limb temperature gradient or capillary refill \>3 seconds
• Clinical/Lab Feature: Reduced conscious level Criteria: AVPU \< "A"

Sponsors & Collaborators

• The Hospital for Sick Children: lead
• Canadian Institutes of Health Research (CIHR): collaborator
• Kamuzu University of Health Sciences: collaborator
• The Eleanor Crook Foundation: collaborator
• Children's Investment Fund Foundation: collaborator
• International Centre for Diarrhoeal Disease Research, Bangladesh: collaborator

Study Sites (2)

International Centre for Diarrheal Disease Research

Dhaka, Bangladesh

Location

Queen Elizabeth Central Hospital

Blantyre, Malawi

Location

Related Publications (7)

• Fivez T, Kerklaan D, Mesotten D, Verbruggen S, Wouters PJ, Vanhorebeek I, Debaveye Y, Vlasselaers D, Desmet L, Casaer MP, Garcia Guerra G, Hanot J, Joffe A, Tibboel D, Joosten K, Van den Berghe G. Early versus Late Parenteral Nutrition in Critically Ill Children. N Engl J Med. 2016 Mar 24;374(12):1111-22. doi: 10.1056/NEJMoa1514762. Epub 2016 Mar 15.

  PMID: 26975590 RESULT

• Maitland K, Berkley JA, Shebbe M, Peshu N, English M, Newton CR. Children with severe malnutrition: can those at highest risk of death be identified with the WHO protocol? PLoS Med. 2006 Dec;3(12):e500. doi: 10.1371/journal.pmed.0030500.

  PMID: 17194194 RESULT

• Kerac M, Bunn J, Seal A, Thindwa M, Tomkins A, Sadler K, Bahwere P, Collins S. Probiotics and prebiotics for severe acute malnutrition (PRONUT study): a double-blind efficacy randomised controlled trial in Malawi. Lancet. 2009 Jul 11;374(9684):136-44. doi: 10.1016/S0140-6736(09)60884-9.

  PMID: 19595348 RESULT

• Hossain M, Chisti MJ, Hossain MI, Mahfuz M, Islam MM, Ahmed T. Efficacy of World Health Organization guideline in facility-based reduction of mortality in severely malnourished children from low and middle income countries: A systematic review and meta-analysis. J Paediatr Child Health. 2017 May;53(5):474-479. doi: 10.1111/jpc.13443. Epub 2017 Jan 4.

  PMID: 28052519 RESULT

• Bhutta ZA, Das JK, Rizvi A, Gaffey MF, Walker N, Horton S, Webb P, Lartey A, Black RE; Lancet Nutrition Interventions Review Group, the Maternal and Child Nutrition Study Group. Evidence-based interventions for improvement of maternal and child nutrition: what can be done and at what cost? Lancet. 2013 Aug 3;382(9890):452-477. doi: 10.1016/S0140-6736(13)60996-4. Epub 2013 Jun 6.

  PMID: 23746776 RESULT

• Bhutta ZA, Berkley JA, Bandsma RHJ, Kerac M, Trehan I, Briend A. Severe childhood malnutrition. Nat Rev Dis Primers. 2017 Sep 21;3:17067. doi: 10.1038/nrdp.2017.67.

  PMID: 28933421 RESULT

• Black RE, Victora CG, Walker SP, Bhutta ZA, Christian P, de Onis M, Ezzati M, Grantham-McGregor S, Katz J, Martorell R, Uauy R; Maternal and Child Nutrition Study Group. Maternal and child undernutrition and overweight in low-income and middle-income countries. Lancet. 2013 Aug 3;382(9890):427-451. doi: 10.1016/S0140-6736(13)60937-X. Epub 2013 Jun 6.

  PMID: 23746772 RESULT

Related Links

• WHO "Levels and trends in child malnutrition"
• WHO "Updates on the management of severe acute malnutrition in infants and children"
• Management of severe malnutrition: a manual for physicians and other senior health workers

MeSH Terms

Conditions

Severe Acute Malnutrition; Child Nutrition Disorders; Infant Nutrition Disorders; Refeeding Syndrome

Condition Hierarchy (Ancestors)

Malnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: This is an open label trial.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Physician, Division of Gastroenterology, Hepatology and Nutrition

Model Details: This is a parallel interventional study model, making use of the Bayesian Continual Reassessment Method to help allocate patients to the different interventional products related to the risk of hypoglycemia compared to F75. The DSMB will be involved in decisions around continuing with a specific interventional product incorporating SAE data.

Study Record Dates

• First Submitted: February 11, 2025
• First Posted: February 26, 2025
• Study Start: February 5, 2025
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: April 24, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

BA (1); MA (1)