Mesalazine in the initial management of severely acutely malnourished children with environmental enteric dysfunction: a pilot randomized controlled trial
<p style="text-align:justify;"><b>Background:</b> Environmental enteric dysfunction (EED) is an acquired syndrome of impaired gastrointestinal mucosal barrier function that is thought to play a key role in the pathogenesis of stunting in early life. It has been conceptua...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
BioMed Central
2014
|
| _version_ | 1826306702974124032 |
|---|---|
| author | Jones, K Hünten-Kirsch, B Laving, A Munyi, C Ngari, M Mikusa, J Mulongo, M Odera, D Nassir, H Timbwa, M Owino, M Fegan, G Murch, S Sullivan, P Warner, J Berkley, J |
| author_facet | Jones, K Hünten-Kirsch, B Laving, A Munyi, C Ngari, M Mikusa, J Mulongo, M Odera, D Nassir, H Timbwa, M Owino, M Fegan, G Murch, S Sullivan, P Warner, J Berkley, J |
| author_sort | Jones, K |
| collection | OXFORD |
| description | <p style="text-align:justify;"><b>Background:</b> Environmental enteric dysfunction (EED) is an acquired syndrome of impaired gastrointestinal mucosal barrier function that is thought to play a key role in the pathogenesis of stunting in early life. It has been conceptualized as an adaptive response to excess environmental pathogen exposure. However, it is clinically similar to other inflammatory enteropathies, which result from both host and environmental triggers, and for which immunomodulation is a cornerstone of therapy.<br/> <b>Methods:</b> In this pilot double-blind randomized placebo-controlled trial, 44 children with severe acute malnutrition and evidence of EED were assigned to treatment with mesalazine or placebo for 28 days during nutritional rehabilitation. Primary outcomes were safety and acceptability of the intervention.<br/> <b>Results:</b> Treatment with mesalazine was safe: there was no excess of adverse events, evidence of deterioration in intestinal barrier integrity or impact on nutritional recovery. There were modest reductions in several inflammatory markers with mesalazine compared to placebo. Depression of the growth hormone - insulin-like growth factor-1 axis was evident at enrollment and associated with inflammatory activation. Increases in the former and decreases in the latter correlated with linear growth.<br/> <b>Conclusions:</b> Intestinal inflammation in EED is non-essential for mucosal homeostasis and is at least partly maladaptive. Further trials of gut-specific immunomodulatory therapies targeting host inflammatory activation in order to optimize the growth benefits of nutritional rehabilitation and to address stunting are warranted. Funded by The Wellcome Trust.<br/> <b>Trial registration:</b> Registered at Clinicaltrials.gov NCT01841099.</p> |
| first_indexed | 2024-03-07T06:51:59Z |
| format | Journal article |
| id | oxford-uuid:fcdc433e-bd09-49e5-a2fe-dbae48d41d16 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:51:59Z |
| publishDate | 2014 |
| publisher | BioMed Central |
| record_format | dspace |
| spelling | oxford-uuid:fcdc433e-bd09-49e5-a2fe-dbae48d41d162022-03-27T13:24:20ZMesalazine in the initial management of severely acutely malnourished children with environmental enteric dysfunction: a pilot randomized controlled trialJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:fcdc433e-bd09-49e5-a2fe-dbae48d41d16EnglishSymplectic Elements at OxfordBioMed Central2014Jones, KHünten-Kirsch, BLaving, AMunyi, CNgari, MMikusa, JMulongo, MOdera, DNassir, HTimbwa, MOwino, MFegan, GMurch, SSullivan, PWarner, JBerkley, J <p style="text-align:justify;"><b>Background:</b> Environmental enteric dysfunction (EED) is an acquired syndrome of impaired gastrointestinal mucosal barrier function that is thought to play a key role in the pathogenesis of stunting in early life. It has been conceptualized as an adaptive response to excess environmental pathogen exposure. However, it is clinically similar to other inflammatory enteropathies, which result from both host and environmental triggers, and for which immunomodulation is a cornerstone of therapy.<br/> <b>Methods:</b> In this pilot double-blind randomized placebo-controlled trial, 44 children with severe acute malnutrition and evidence of EED were assigned to treatment with mesalazine or placebo for 28 days during nutritional rehabilitation. Primary outcomes were safety and acceptability of the intervention.<br/> <b>Results:</b> Treatment with mesalazine was safe: there was no excess of adverse events, evidence of deterioration in intestinal barrier integrity or impact on nutritional recovery. There were modest reductions in several inflammatory markers with mesalazine compared to placebo. Depression of the growth hormone - insulin-like growth factor-1 axis was evident at enrollment and associated with inflammatory activation. Increases in the former and decreases in the latter correlated with linear growth.<br/> <b>Conclusions:</b> Intestinal inflammation in EED is non-essential for mucosal homeostasis and is at least partly maladaptive. Further trials of gut-specific immunomodulatory therapies targeting host inflammatory activation in order to optimize the growth benefits of nutritional rehabilitation and to address stunting are warranted. Funded by The Wellcome Trust.<br/> <b>Trial registration:</b> Registered at Clinicaltrials.gov NCT01841099.</p> |
| spellingShingle | Jones, K Hünten-Kirsch, B Laving, A Munyi, C Ngari, M Mikusa, J Mulongo, M Odera, D Nassir, H Timbwa, M Owino, M Fegan, G Murch, S Sullivan, P Warner, J Berkley, J Mesalazine in the initial management of severely acutely malnourished children with environmental enteric dysfunction: a pilot randomized controlled trial |
| title | Mesalazine in the initial management of severely acutely malnourished children with environmental enteric dysfunction: a pilot randomized controlled trial |
| title_full | Mesalazine in the initial management of severely acutely malnourished children with environmental enteric dysfunction: a pilot randomized controlled trial |
| title_fullStr | Mesalazine in the initial management of severely acutely malnourished children with environmental enteric dysfunction: a pilot randomized controlled trial |
| title_full_unstemmed | Mesalazine in the initial management of severely acutely malnourished children with environmental enteric dysfunction: a pilot randomized controlled trial |
| title_short | Mesalazine in the initial management of severely acutely malnourished children with environmental enteric dysfunction: a pilot randomized controlled trial |
| title_sort | mesalazine in the initial management of severely acutely malnourished children with environmental enteric dysfunction a pilot randomized controlled trial |
| work_keys_str_mv | AT jonesk mesalazineintheinitialmanagementofseverelyacutelymalnourishedchildrenwithenvironmentalentericdysfunctionapilotrandomizedcontrolledtrial AT huntenkirschb mesalazineintheinitialmanagementofseverelyacutelymalnourishedchildrenwithenvironmentalentericdysfunctionapilotrandomizedcontrolledtrial AT lavinga mesalazineintheinitialmanagementofseverelyacutelymalnourishedchildrenwithenvironmentalentericdysfunctionapilotrandomizedcontrolledtrial AT munyic mesalazineintheinitialmanagementofseverelyacutelymalnourishedchildrenwithenvironmentalentericdysfunctionapilotrandomizedcontrolledtrial AT ngarim mesalazineintheinitialmanagementofseverelyacutelymalnourishedchildrenwithenvironmentalentericdysfunctionapilotrandomizedcontrolledtrial AT mikusaj mesalazineintheinitialmanagementofseverelyacutelymalnourishedchildrenwithenvironmentalentericdysfunctionapilotrandomizedcontrolledtrial AT mulongom mesalazineintheinitialmanagementofseverelyacutelymalnourishedchildrenwithenvironmentalentericdysfunctionapilotrandomizedcontrolledtrial AT oderad mesalazineintheinitialmanagementofseverelyacutelymalnourishedchildrenwithenvironmentalentericdysfunctionapilotrandomizedcontrolledtrial AT nassirh mesalazineintheinitialmanagementofseverelyacutelymalnourishedchildrenwithenvironmentalentericdysfunctionapilotrandomizedcontrolledtrial AT timbwam mesalazineintheinitialmanagementofseverelyacutelymalnourishedchildrenwithenvironmentalentericdysfunctionapilotrandomizedcontrolledtrial AT owinom mesalazineintheinitialmanagementofseverelyacutelymalnourishedchildrenwithenvironmentalentericdysfunctionapilotrandomizedcontrolledtrial AT fegang mesalazineintheinitialmanagementofseverelyacutelymalnourishedchildrenwithenvironmentalentericdysfunctionapilotrandomizedcontrolledtrial AT murchs mesalazineintheinitialmanagementofseverelyacutelymalnourishedchildrenwithenvironmentalentericdysfunctionapilotrandomizedcontrolledtrial AT sullivanp mesalazineintheinitialmanagementofseverelyacutelymalnourishedchildrenwithenvironmentalentericdysfunctionapilotrandomizedcontrolledtrial AT warnerj mesalazineintheinitialmanagementofseverelyacutelymalnourishedchildrenwithenvironmentalentericdysfunctionapilotrandomizedcontrolledtrial AT berkleyj mesalazineintheinitialmanagementofseverelyacutelymalnourishedchildrenwithenvironmentalentericdysfunctionapilotrandomizedcontrolledtrial |