Therapeutic Approaches to Malnutrition Enteropathy

Summary

The TAME study will evaluate four new approaches which will be compared against the standard care currently in use in the treatment of malnutrition enteropathy in children with severe acute malnutrition. A high pathogen burden causes damage to the intestinal mucosa which exacerbates nutritional impairment and leads to further susceptibility to infection and impaired epithelial regeneration. Enteropathy is characterised by multiple epithelial breaches, microbial translocation from gut lumen to systemic circulation and systemic inflammation.The trial will evaluate the potential impact of four interventions (colostrum, N-acetyl glucosamine, teduglutide, and budesonide) given for 14 days, which aim at mucosal restoration. The trial will determine if repairing damage to the small intestinal mucosa leads to the reduction of systemic inflammation and thus lessening the nutritional impairment, and so if this contributes to the reduction of mortality in children. In Zambia only, endoscopic biopsies and confocal laser endomicroscopy will be used to evaluate response and confirm safety at a mucosal level. Identifying an agent or agents which contribute most to mucosal healing will then ultimately lead to further large phase 3 trial in which the agent(s) will be further evaluated. The trial also anticipates to gain a more in depth understanding of pathophysiology and may identify where current management strategies of treating malnutrition enteropathy in children are failing.

Timeline

Start

2020-05-04

Primary completion

2021-04-27

Completion

2021-04-27

Publications

• Chandwe K, Bwakura-Dangarembizi M, Amadi B, Tawodzera G, Ngosa D, Dzikiti A, Chulu N, Makuyana R, Zyambo K, Mutasa K, Mulenga C, Besa E, Sturgeon JP, Mudzingwa S, Simunyola B, Kazhila L, Zyambo M, Sonkwe H, Mutasa B, Chipunza M, Sauramba V, Langhaug L, Mudenda V, Murch SH, Hill S, Playford RJ, VanBuskirk K, Prendergast AJ, Kelly P. Malnutrition enteropathy in Zambian and Zimbabwean children with severe acute malnutrition: A multi-arm randomized phase II trial. Nat Commun. 2024 Apr 17;15(1):2910. doi: 10.1038/s41467-024-45528-0.
• Kelly P, Bell L, Amadi B, Bwakura-Dangarembizi M, VanBuskirk K, Chandwe K, Chipunza M, Ngosa D, Chulu N, Hill S, Murch S, Playford R, Prendergast A. TAME trial: a multi-arm phase II randomised trial of four novel interventions for malnutrition enteropathy in Zambia and Zimbabwe - a study protocol. BMJ Open. 2019 Nov 14;9(11):e027548. doi: 10.1136/bmjopen-2018-027548.

Drugs

Indications