Pancreatic Enzymes and Bile Acids in Acutely Ill Severely Malnourished Children

• Status: Not yet recruiting
• Trial end date: 2024-06-30
• Target enrollment: 0
• Participant gender: All

Summary

Children with severe malnutrition who are sick and admitted to hospitals have high mortality, usually because of infection. Malnourished children have more potentially harmful bacteria in their upper intestines than well-nourished children and this may contribute to inflammation in the gut and whole body. These bacteria may cross from the intestines to the bloodstream causing life-threatening infections. A related abnormality among malnourished children is reduction in the digestive enzymes made by the pancreas and the liver. Apart from helping with digestion of food, these enzymes are important in helping the body control bacteria in the upper intestines. It is therefore possible that treatment with digestive enzymes could help reduce the burden of harmful bacteria and thus lower inflammation and the risk of serious infection. One study conducted in Malawi has shown that children with severe malnutrition who were supplemented with pancreatic enzymes had a lower risk of dying. However, this was a small study and although promising, requires validation. No studies of supplementation with bile acids have been done among severely malnourished children. However, bile acids are commonly used to manage patients with liver function abnormalities, something that malnourished children suffer from as well. The investigators want to find out if supplementing these pancreatic enzymes and bile acids among ill children with severe acute malnutrition is safe and reduces the risk of death, deterioration or readmission to hospital.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Oxford
• Collaborators: International Centre for Diarrhoeal Disease Research, Bangladesh; KEMRI-Wellcome Trust Collaborative Research Program; Kenya Medical Research Institute; Makerere University; Oregon Health and Science University; Queen Elizabeth Central Hospital, Blantyre, Malawi; University of Amsterdam; University of Toronto; University of Washington
• Treatments: Ursodeoxycholic Acid

Criteria

Inclusion Criteria:

• Age 2 to <59 months

• Admitted to hospital with an acute, non-traumatic illness and within 72 hours of admission at the time of enrolment

• Severe malnutrition (weight-for-height <-3 z scores of the median WHO growth standards and/or mid upper arm circumference <115mm (<110mm age below 6 months), or symmetrical oedema of at least the feet related to malnutrition (not related to a primary cardiac or renal disorder)

• Able to feed orally in usual state of health.

• Accompanied by care provider who provides written informed consent

• Primary caregiver plans to stay in the study area during the duration of the study

• Presence of two or more features of severity as specified below. If a child meets two criteria, they may be enrolled before further criteria are assessed (e.g. a child may be eligible on clinical signs before the complete blood count results are known):

Respiratory distress "Subcostal indrawing" or "nasal flaring" or "head-nodding" Oxygenation "Central cyanosis" or SaO2 <90% Circulation Limb temperature gradient or capillary refill >3 seconds Conscious level AVPU < "A" Pulse > 180 per min Haemoglobin < 7g/dl Blood glucose < 3mmol/L White blood cells < 4 or > 17.5 x 109/L Temperature <36 or >38.5oC Very low MUAC MUAC <11cm

Exclusion Criteria: