Reformulated F75 Milk to Treat Severe Acute Malnutrition

NCT02246296 | Completed Phase 2 DMC

• 3 other identifiers: OXTREC 58-14P.03/14/1540SSC 2799
• Study Type: interventional
• Target: 842
• Locations: 2 countries
• Sites: 3

Brief Summary

Inpatient treatment for complicated severe acute malnutrition (SAM) continues to have a high mortality in Africa. This is partly because children are commonly brought for admission because they are seriously ill, rather than being brought to hospital because of malnutrition alone. Mortality rates are especially high where SAM is complicated by HIV or TB. The early phase of inpatient nutritional treatment for severe acute malnutrition is based on a low-protein milk known as F75, which is given to improve metabolic homeostasis prior to the re-feeding to achieve catch-up growth. F75 provides a high proportion of energy from carbohydrates, including sucrose, lactose and maltodextrin. However, malabsorption of different types of carbohydrates, but lactose in particular, is known to occur in SAM and may lead to osmotic diarrhoea. Diarrhoea is common in children with SAM and is associated with increased mortality. Furthermore, switching from a catabolic state to a high energy diet that consists of predominantly carbohydrates can lead to 're-feeding syndrome' that may lead to severe electrolyte abnormalities and multiple organ dysfunction. The aim of this trial is to determine whether reducing the carbohydrate content of F75, and removing lactose, improves the stabilisation of severely malnourished children. The trial will involve randomising children who are eligible to receive F75 milk to either the current formulation or a revised formulation. Both formulations will be given according to current recommendations regarding frequency of feeding and caloric value. Since the purpose of F75 is to stabilise the child metabolically and biochemically, the primary endpoint of the trial will be time to stabilisation (the end of the first phase of treatment for severe acute malnutrition). Blood and stool samples at admission and after three days will be used to determine the effects on carbohydrate and fat malabsorption and evidence of the re-feeding syndrome. Children will be followed up until discharge from hospital. The project has been planned in consultation with the World Health Organisation (WHO) and, if the revised formulation of F75 results in improved outcomes, will lead to a global change in recommendations for its formulation.

Conditions

Malnutrition; Diarrhoea; Metabolic Disturbance

Keywords

severe acute malnutrition; wasting; kwashiorkor; nutrition; feeding; milk

Outcome Measures

Primary Outcomes (1)

• Time to Stabilization

  The criteria for stabilisation will be according to WHO guidelines: \- Absence of any WHO danger or emergency signs: obstructed breathing, respiratory distress, cyanosis, shock (delayed capillary refill plus fast \& weak pulse plus temperature gradient), severe anaemia (Hb\<5g/dl), congestive cardiac failure, impaired consciousness, convulsions, severe dehydration, profuse watery diarrhoea, vomits everything, hypothermia. and If there is oedema at baseline, loss of oedema defined as improving from a severe +++ oedema (severe: generalized bilateral pitting oedema including feet, legs, arms and face) to ++ oedema (moderate: no upper arm or upper leg oedema and no facial oedema or from ++ oedema to + (mild: only feet/ankle oedema) or none; and Tolerating full prescribed volume of F75 feeds and observed to be completing the feeds.

  During inpatient admission

Secondary Outcomes (9)

• Number days with diarrhoea

  Upto discharge from hospital participants will be followed for the duration of hospital stay, an expected average of 2 weeks

• Number days requiring rehydration fluids

  Upto discharge from hospital, an expected average of 2 weeks

• Percentage change in weight to day 5

  Up to day 5 of admission

• Change in electrolyte serum electrolytes to day 3

  Between baseline (admission) and day 3

• Number of new onset severe clinical deterioration

  Upto discharge from hospital, an expected average of 2 weeks

Study Arms (2)

Standard F75 Milk

ACTIVE COMPARATOR

F75 with 63% of total energy from carbohydrates, including 10% of energy from lactose (standard F75).

Dietary Supplement: Standard F75 Milk

Modified F75 Milk

EXPERIMENTAL

F75 milk with 43% of total energy from carbohydrates, without any lactose, and providing the same amount of energy as standard F75 by increased lipid in the form of medium chain triglycerides.

Dietary Supplement: Modified F75 Milk

Interventions

Standard F75 Milk DIETARY_SUPPLEMENT

This is the standard F75 milk used worldwide (Control group)

Also known as: Standard formulation F75 therapeutic milk

Standard F75 Milk

Modified F75 Milk DIETARY_SUPPLEMENT

This is the experimental group

Also known as: Modified formulation F75 Milk

Modified F75 Milk

Eligibility Criteria

• Age: 6 Months - 13 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age 6 months to 13 years
• Severe malnutrition defined as: mid upper arm circumference (MUAC) \<11.5cm if less than 5 years old;19 or weight for height Z score \<-3; or kwashiorkor as defined in the current Kenyan and WHO guidelines.
• Admitted to hospital because of medical complications or failure of an appetite test as defined in the current WHO guidelines.
• Eligible to start F75 milk by current WHO guidelines.

You may not qualify if:

• Declined to give informed consent.
• Known allergy to milk products.
• Any other reason the consenting investigator thinks that in the child's best interests it inappropriate for them to take part.

Sponsors & Collaborators

• University of Oxford: lead
• KEMRI-Wellcome Trust Collaborative Research Program: collaborator
• Kamuzu University of Health Sciences: collaborator
• The Hospital for Sick Children: collaborator
• University of Groningen: collaborator

Study Sites (3)

Kilifi County Hospital

Kilifi, Coast, 80108, Kenya

Location

Coast Provincial General Hospital - Study site

Mombasa, Kenya

Location

Queen Elizabeth Hospital- Study site

Blantyre, Malawi

Location

Related Publications (4)

• Wen B, Brals D, Bourdon C, Erdman L, Ngari M, Chimwezi E, Potani I, Thitiri J, Mwalekwa L, Berkley JA, Bandsma RHJ, Voskuijl W. Predicting the risk of mortality during hospitalization in sick severely malnourished children using daily evaluation of key clinical warning signs. BMC Med. 2021 Sep 20;19(1):222. doi: 10.1186/s12916-021-02074-6.

  PMID: 34538239 DERIVED

• van den Brink DA, de Meij T, Brals D, Bandsma RHJ, Thitiri J, Ngari M, Mwalekwa L, de Boer NKH, Wicaksono A, Covington JA, van Rheenen PF, Voskuijl WP. Prediction of mortality in severe acute malnutrition in hospitalized children by faecal volatile organic compound analysis: proof of concept. Sci Rep. 2020 Nov 5;10(1):18785. doi: 10.1038/s41598-020-75515-6.

  PMID: 33154417 DERIVED

• Bitilinyu-Bangoh J, Voskuijl W, Thitiri J, Menting S, Verhaar N, Mwalekwa L, de Jong DB, van Loenen M, Mens PF, Berkley JA, Bandsma RHJ, Schallig HDFH. Performance of three rapid diagnostic tests for the detection of Cryptosporidium spp. and Giardia duodenalis in children with severe acute malnutrition and diarrhoea. Infect Dis Poverty. 2019 Nov 28;8(1):96. doi: 10.1186/s40249-019-0609-6.

  PMID: 31775877 DERIVED

• Bandsma RHJ, Voskuijl W, Chimwezi E, Fegan G, Briend A, Thitiri J, Ngari M, Mwalekwa L, Bandika V, Ali R, Hamid F, Owor B, Mturi N, Potani I, Allubha B, Muller Kobold AC, Bartels RH, Versloot CJ, Feenstra M, van den Brink DA, van Rheenen PF, Kerac M, Bourdon C, Berkley JA. A reduced-carbohydrate and lactose-free formulation for stabilization among hospitalized children with severe acute malnutrition: A double-blind, randomized controlled trial. PLoS Med. 2019 Feb 26;16(2):e1002747. doi: 10.1371/journal.pmed.1002747. eCollection 2019 Feb.

  PMID: 30807589 DERIVED

Related Links

• College of Medicine, Blantyre, Malawi.
• KEMRI/Wellcome Trust Research Programme
• Sick Kids, Toronto

MeSH Terms

Conditions

Malnutrition; Diarrhea; Severe Acute Malnutrition; Cachexia; Kwashiorkor

Condition Hierarchy (Ancestors)

Nutrition Disorders; Nutritional and Metabolic Diseases; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Weight Loss; Body Weight Changes; Body Weight; Thinness

Study Officials

• James A Berkley

  KEMRI-Wellcome Trust Research Kilifi, Kenya

  PRINCIPAL INVESTIGATOR

• Wieger Voskuijl

  University of Medicine, Blantye Malawi

  PRINCIPAL INVESTIGATOR

• Robert Bandsma, PhD

  The Hospital for Sick Children, Toronto, Canada

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2014
• First Posted: September 22, 2014
• Study Start: December 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: April 14, 2016

Record last verified: 2016-04

Locations

KE (2); MA (1)