Clinical trial NCT01841099: Mesalamine in Environmental Enteropathy
Official title: Randomised Placebo-controlled Trial of a Gut Immunomodulatory Agent (Mesalamine) to Tackle Environmental Enteropathy in Acutely Malnourished Children: A Pilot Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Malnutrition
Lead sponsor: KEMRI-Wellcome Trust Collaborative Research Program
Sponsor class: OTHER
Collaborators: name: Imperial College London
First posted: 2013-04-26
Enrollment: 44
Sex: ALL
Minimum age (years): 1
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Undernutrition is one of the most important health issues in Kenya. Children who are chronically undernourished do not reach their full potential and are at increased risk of infectious disease. Stunting occurs in a third of Kenyan children and has severe and long-term consequences in terms of health, development, and poverty. Several studies have shown that stunting is frequently associated with subclinical inflammation of the bowel, a condition referred to as Environmental Enteropathy (EE), previously known as 'tropical sprue' or 'tropical enteropathy'. EE is clinically similar to childhood inflammatory bowel diseases (IBD), including Crohn's disease. The treatment of IBD routinely involves provision of gut immunomodulatory agents, but this approach has never been tried in EE.

This proposal outlines a pilot double-blind randomised placebo-controlled trial of mesalamine (also called mesalazine - the safest immunomodulator used in IBD with least systemic activity) in treatment of severely malnourished children with EE.


Eligibility criteria: Inclusion Criteria:

* Children aged 1 to 5 years old.
* Provision of informed consent by parent or guardian.
* Stunting (height for age z score \<-2)
* Severe malnutrition (one or more of mid-upper arm circumference \<11.5cm, weight for height z score \<-3, or nutritional oedema).
* Eligible for outpatient management of malnutrition (i.e. no evidence of acute infection, and passes 'appetite test' according to national guidelines).
* Evidence of chronic inflammation (elevated erythrocyte sedimentation rate, ESR \>20mm/hr).

Exclusion Criteria:

* Known HIV disease or tuberculosis.
* Known previous renal disease or asthma.
* Known allergy or hypersensitivity to mesalamine, other salicylate drugs, or any of the product ingredients.
* Biochemical evidence of acute renal or hepatic impairment on screening blood tests.
* Thrombocytopenia
* Recent (previous two weeks) bloody diarrhoea.
* Concurrent medication known to interact with the study drug (non-steroidal anti-inflammatory drugs, ranitidine, proton-pump inhibitors)
* Acute infection requiring treatment, e.g. lower respiratory tract infection or febrile illness.
* Other reason at the discretion of the attending clinician (independent of the trial team).

Primary outcomes:
measure: Frequency of adverse events/serious adverse events
timeFrame: Day 0 to day 28 and day 0 to day 56
measure: Compliance with treatment
timeFrame: Day 0 to day 28
Secondary outcomes:
measure: Changes in height
timeFrame: Day 0 to 28 and day 0 to day 56
measure: Changes in levels of anti-Endotoxin Core IgG (EndoCAb)
timeFrame: Day 0 - Day 28 and Day 0 - Day 56
measure: Changes in fecal calprotectin levels
timeFrame: Day 0 - Day 28 and Day 0 - Day 56
measure: Changes in plasma soluble-CD14
timeFrame: Day 0 - Day 28 and Day 0 - Day 56
measure: Changes in plasma beta-2 microglobulin
timeFrame: Day 0 - Day 28 and Day 0 - Day 56
measure: Changes in plasma neopterin
timeFrame: Day 0 - Day 28 and Day 0 - Day 56
measure: Changes in weight
timeFrame: Day 0 - Day 28 and Day 0 - Day 56
measure: Changes in mid-upper arm circumference
timeFrame: Day 0 - Day 28 and Day 0 - Day 56
measure: Changes in C-Reactive Protein
timeFrame: Day 0 - Day 28, and Day 0 - Day56
Other outcomes:
Locations:
city: Nairobi
country: Kenya
facility: Baraka Clinic
state: Mathare
Study officials:
affiliation: KEMRI-Wellcome Trust Research Programme and Imperial College London
name: Kelsey DJ Jones, MBBS BA MRCPCH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jones KD, Hunten-Kirsch B, Laving AM, Munyi CW, Ngari M, Mikusa J, Mulongo MM, Odera D, Nassir HS, Timbwa M, Owino M, Fegan G, Murch SH, Sullivan PB, Warner JO, Berkley JA. Mesalazine in the initial management of severely acutely malnourished children with environmental enteric dysfunction: a pilot randomized controlled trial. BMC Med. 2014 Aug 14;12:133. doi: 10.1186/s12916-014-0133-2.