Mesalamine in Environmental Enteropathy

NCT01841099 | Completed Phase 1 DMC

• 2 other identifiers: KEMRI_CT_2013/0016SSC 2223
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

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.

Conditions

Malnutrition

Outcome Measures

Primary Outcomes (2)

• Frequency of adverse events/serious adverse events

  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

  Day 0 to day 28 and day 0 to day 56

• Compliance with treatment

  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

  Day 0 to day 28

Secondary Outcomes (9)

• Changes in height

  Day 0 to 28 and day 0 to day 56

• Changes in levels of anti-Endotoxin Core IgG (EndoCAb)

  Day 0 - Day 28 and Day 0 - Day 56

• 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

Study Arms (2)

Mesalamine

EXPERIMENTAL

Mesalamine. Mesalamine granules. 30 mg/kg/day oral for 7 days followed by 50 mg/kg/day oral for 21 days if tolerated.

Drug: Mesalamine

Placebo granules

PLACEBO COMPARATOR

Placebo granules

Drug: Placebo granules

Interventions

Mesalamine DRUG

Mesalamine granules

Also known as: Mesalazine, Pentasa (trade name)

Mesalamine

Placebo granules DRUG

Provided by Ferring Pharma

Placebo granules

Eligibility Criteria

• Age: 1 Year - 5 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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).

You may not qualify if:

• 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).

Sponsors & Collaborators

• Kelsey Jones: lead
• Imperial College London: collaborator

Study Sites (1)

Baraka Clinic

Nairobi, Mathare, Kenya

Location

Related Publications (1)

• 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.

  PMID: 25189855 DERIVED

MeSH Terms

Conditions

Malnutrition

Interventions

Mesalamine

Condition Hierarchy (Ancestors)

Nutrition Disorders; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

meta-Aminobenzoates; Aminobenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Aminosalicylic Acids; Salicylates; Hydroxybenzoates; Hydroxy Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenols

Study Officials

• Kelsey DJ Jones, MBBS BA MRCPCH

  KEMRI-Wellcome Trust Research Programme and Imperial College London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Study Principal Investigator

Study Record Dates

• First Submitted: April 15, 2013
• First Posted: April 26, 2013
• Study Start: June 1, 2013
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: July 11, 2014

Record last verified: 2014-07

Locations

KE (1)