Malnutrition
Conditions
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.
Interventions
DRUGMesalamine
Mesalamine granules
DRUGPlacebo granules
Provided by Ferring Pharma
Sponsors
Imperial College London
Kelsey Jones
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
1 Years to 5 Years
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of adverse events/serious adverse events | Day 0 to day 28 and day 0 to day 56 | This trial represents the first time a member of a class of drugs are to be used in a particular vulnerable group patient group. It's primary purpose is to conduct an early evaluation of safety and acceptability in this and the study is not powered to address any specific outcomes. It represents a modified Phase IIa design |
| Compliance with treatment | Day 0 to day 28 | This trial represents the first time a member of a class of drugs are to be used in a particular vulnerable group patient group. It's primary purpose is to conduct an early evaluation of safety and acceptability in this and the study is not powered to address any specific outcomes. It represents a modified Phase IIa design |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in fecal calprotectin levels | Day 0 - Day 28 and Day 0 - Day 56 | — |
| Changes in plasma soluble-CD14 | Day 0 - Day 28 and Day 0 - Day 56 | — |
| Changes in plasma beta-2 microglobulin | Day 0 - Day 28 and Day 0 - Day 56 | — |
| Changes in height | Day 0 to 28 and day 0 to day 56 | mm/day |
| Changes in weight | Day 0 - Day 28 and Day 0 - Day 56 | g/kg/day |
| Changes in mid-upper arm circumference | Day 0 - Day 28 and Day 0 - Day 56 | mm/day |
| Changes in C-Reactive Protein | Day 0 - Day 28, and Day 0 - Day56 | — |
| Changes in plasma neopterin | Day 0 - Day 28 and Day 0 - Day 56 | — |
| Changes in levels of anti-Endotoxin Core IgG (EndoCAb) | Day 0 - Day 28 and Day 0 - Day 56 | — |
Countries
Kenya
Outcome results
None listed