Pancreatic Enzymes and Bile Acids in Acutely Ill Severely Malnourished Children
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.
Timeline
- Start
- 2021-07-01
- Primary completion
- 2023-10-31
- Completion
- 2024-06-30
Publications
- Background Zhang L, Voskuijl W, Mouzaki M, Groen AK, Alexander J, Bourdon C, Wang A, Versloot CJ, Di Giovanni V, Wanders RJ, Bandsma R. Impaired Bile Acid Homeostasis in Children with Severe Acute Malnutrition. PLoS One. 2016 May 10;11(5):e0155143. doi: 10.1371/journal.pone.0155143. eCollection 2016.
- Background Bartels RH, Bourdon C, Potani I, Mhango B, van den Brink DA, Mponda JS, Muller Kobold AC, Bandsma RH, Boele van Hensbroek M, Voskuijl WP. Pancreatic Enzyme Replacement Therapy in Children with Severe Acute Malnutrition: A Randomized Controlled Trial. J Pediatr. 2017 Nov;190:85-92.e2. doi: 10.1016/j.jpeds.2017.07.013. Epub 2017 Sep 11.
- Background Njunge JM, Gwela A, Kibinge NK, Ngari M, Nyamako L, Nyatichi E, Thitiri J, Gonzales GB, Bandsma RHJ, Walson JL, Gitau EN, Berkley JA. Biomarkers of post-discharge mortality among children with complicated severe acute malnutrition. Sci Rep. 2019 Apr 12;9(1):5981. doi: 10.1038/s41598-019-42436-y.
- Background Attia S, Versloot CJ, Voskuijl W, van Vliet SJ, Di Giovanni V, Zhang L, Richardson S, Bourdon C, Netea MG, Berkley JA, van Rheenen PF, Bandsma RH. Mortality in children with complicated severe acute malnutrition is related to intestinal and systemic inflammation: an observational cohort study. Am J Clin Nutr. 2016 Nov;104(5):1441-1449. doi: 10.3945/ajcn.116.130518. Epub 2016 Sep 21.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Comparator | Pancrelipase | Protein / enzyme biologic | 3000 iu/kg | — |
| Comparator | Ursodeoxycholic Acid | Small molecule | 10 mg/kg | — |