The effect of rice-based, lactose-free F-75 therapeutic formula on diarrhoea in the treatment of children with severe acute malnutrition

• Register: ISRCTN
• Last refreshed on: 27 May 2019
• Main ID: ISRCTN98124592
• Date of registration: 15/08/2017
• Prospective Registration: Yes
• Primary sponsor: University of Copenhagen
• Public title: The effect of rice-based, lactose-free F-75 therapeutic formula on diarrhoea in the treatment of children with severe acute malnutrition
• Scientific title: The effect of modified F-75 on diarrhoea in the treatment of children with severe acute malnutrition – a randomized controlled 2x2 factorial trial in Uganda
• Date of first enrolment: 16/08/2017
• Target sample size: 450
• Recruitment status: Stopped
• URL: http://isrctn.com/ISRCTN98124592
• Study type: Interventional
• Study design: Randomized controlled double-blind two-by-two factorial trial (Treatment)
• Phase: Not Applicable

Countries of recruitment

Uganda

Contacts

• Name: Henrik Friis

Key inclusion & exclusion criteria

Inclusion criteria:
1. Age 6 – 59 months
2. Children with severe acute malnutrition (MUAC < 11.5 cm or weight-for-height z-score < -3 SD or bipedal pitting oedema)
3. Indication for in-patient treatment (oedema above the knees (grade +++)), or failing an appetite test, or medical complications requiring hospitalization
4. Written informed consent obtained

Exclusion criteria:
1. Obvious disability and congenital diseases which may affect eating capabilities
2. Weight below 3.0 kg at admission
3. Malignant diseases
4. Patients participating in another study that may interfere with the current study
5. Patients started on F-75 treatment more than 18 hours before recruitment to the study


Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Severe acute malnutrition (SAM)
Nutritional, Metabolic, Endocrine
Malnutrition

Intervention(s)

Four study arms will receive modified F-75 as a replacement of standard F-75. F-75 is a therapeutic food used during stabilization of hospitalized children with severe acute malnutrition. Randomisation will be individual, stratified by diarrhoea status at enrolment, and using varying block size.
1. Maltodextrin-based F-75, standard lactose (standard F-75)
2. Maltodextrin-based F-75, no lactose (<0.02g/100 ml)
3. Rice-based F-75, standard lactose
4. Rice-based F-75, no lactose (<0.02g/100ml)
The amount of energy and the energy distribution (carbohydrate, protein and fat) will be similar in the four therapeutic foods. The amount of modified F-75 is given in accordance with the WHO protocol for treatment of hospitalized children with severe acute malnutrition. In addition, a daily dose of fish oil will be given to all study children to meet their requirements for n-3 LCPUFA during inpatient treatment.

The duration of the stabilization phase is typically around one week. The trial ends when children are discharged from the nutrition unit. Children are monitored daily by medical doctors and nutritionists. Blood and stool samples are collected at baseline, day 2, transition of feeds and at discharge to measure blood electrolytes, stool pH and biomarkers of gut health, infection (at admission only) and fatty acid profile. Anthropometry is measured at admission and discharge and weight is measured daily. Diarrhoea will be monitored closely by use of a stool diary with ongoing registration of stool frequency, stool consistency, vomiting and fever.

50 healthy control children of the same age and from the same area will be included to collect reference samples of blood and stool and body measurements.

Primary Outcome(s)

Number of days with diarrhoea during treatment with modified F-75, measured using a validated stool diary daily from admission to transition

Secondary Outcome(s)

1. Number of days with diarrhoea during hospitalization, measured using a validated stool diary daily from admission to discharge
2. Incidence of diarrhoea, defined as the proportion of children with minimum one day of diarrhoea, measured at transition and discharge
3. Severity of diarrhoea, assessed using the Vesikari scale daily
4. Consumption and feeding patterns:
4.1. Food intake in ml and duration of the meal measured as 3 time categories daily from admission to transition
4.2. Acceptability using a 5-point hedonic scale on day 2 and at transition
5. Number of days of the first stabilization phase and total number of days spent in the stabilization phase if the child deteriorates and resumes stabilization treatment. Duration of the first stabilization period is defined as: total number of days from admission to the day the child is considered stabilized for the first time. Total number of days spent in stabilization is defined as the total number of days whereby a child is “in the stabilization phase”. It includes the first stabilization phase and any periods when the child may go back to the stabilization phase due to deterioration of health. A child is considered to be stabilized when all these criteria are fulfilled: 1) Return of appetite; the child easily finishes all the prescribed feeds of F-75 and demands for more; 2) Reduced or minimal bilateral pitting oedema (reduced to grade 2 or grade 1); 3) Medical complications resolving; the child may also smile at this stage.
6. Number of days of hospital stay, calculated from the day of admission to discharge. Both days are included in hospitalization duration
7. Plasma electrolyte concentrations (P, Mg, K, Na, Cl, bicarbonate) measured at admission, two days after admission and at transition
8. Degree of dehydration (no, some, severe dehydration and shock), assessed at transition and discharge. Dehydration measured daily throughout hospitalization according to the WHO/Ugandan IMAM guidelines for assessment and treatment of dehydration in severely malnourished children. The highest degree of dehydration in the previous 24 hours is noted
9. Number of new onset severe clinical deteriorations, measured daily during hospitalization, defined as a new onset of any of the WHO danger signs:
9.1. Severe dehydration
9.2. Shock (lethargic or unconscious and has cold peripheries as well as either capillary refill time >3 secs or fast and weak pulse)
9.3. Severe respiratory distress (respiratory rate = 40/50 bpm for children above/below 1 year respectively and severe chest in-drawing, grunting, nasal flaring, central cyanosis and hypoxemia (SPO2<90%)
9.4. Impaired consciousness (modified Glasgow coma scale < 15)
9.5. Cardiac failure (the cardinal signs of cardiac failure includes: tachycardia, tachypnoea, tender hepatomegaly)
9.6. Hypoglycemia (blood glucose less than 3 mmol/l)
9.7. Hypothermia (temperature below 35?C, axillary temperature)
9.8. Hyperthermia (temperature above 39.5?C, axillary temperature)
9.9. Severe anaemia (Hb below 4g/dl)
9.10. Convulsions
10. Child development, measured using the Malawi Developmental Assessment Tool at discharge

Auxiliary outcomes:
1. Mortality during hospitalization
2. Stool pH and reducing substances, measured using pH strips and Benedict’s solution at admission, day 2 and transition and if lactose intolerance is suspected
3. Gut microbiota, measured using 16S rRNA gene amplicon Illumina based high throughput sequencing at admission, transition and discharge
4. Gut function: plasma citrulline, faecal myeloperoxidase and faecal neopterine measured using mass spectrometry/ELISA test at admission, transition and discharge
5. Body composition, measured using bio-electrical impedance analysis at discharge
6. Fatty acid profile, measured using high-throughput GLC on whole blood dry blood spots at admission, transition and discharge

Secondary ID(s)

D219

Source(s) of Monetary Support

Mejeribrugets ForskningsFond, US Dairy Export Council, Københavns Universitet

Ethics review

Status:
Approval date:
Contact:

1. Uganda: School of Medicine Research and Ethics committee (SOMREC) at Makerere University, 06/10/2016, ref: 2016-103; amendment approved 10/07/2017 2. Denmark: The National Committee on Health Research Ethics, 18/01/2017

Results

• Results available: Yes
• Date Completed: 31/08/2019