Therapeutic Approaches to Malnutrition Enteropathy

• Status: Completed
• Trial end date: 2021-04-27
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Queen Mary University of London
• Treatments: Budesonide; Teduglutide

Criteria

Inclusion Criteria:

1. Age 6 - 59 months, of either sex;

2. Inpatient in the paediatric wards of one of the research sites;

3. Hospitalised with Severe Acute Malnutrition (SAM, defined using WHO definition:

weight-for-length z score of less than -3, or mid upper arm circumference of less than 11.5cm, and/or bilateral pedal oedema);

4. Clinically stable*;

5. With written, informed consent from the primary caregiver(s); the child cannot be enrolled if the primary caregiver(s) cannot give consent.

• Judged by the medical team on a case by case basis, but in general a child without shock, hypothermia, hypoglycaemia or reduced conscious level.

Exclusion Criteria:

1. Clinically unstable*;

2. Less than 5kg body weight;

3. Neurological disability which would explain or partly explain poor feeding;

4. Oro-facial abnormalities which would explain or partly explain poor feeding;

5. Caregiver unwilling to consent to child HIV testing;

6. Haemoglobin concentration < 6 g/dl at the time of enrolment;

7. Caregiver unwilling to remain in hospital for the duration of the study treatment;

8. Any underlying condition, other than HIV, which in the opinion of the investigator would put the subject at undue risk of failing study completion or would interfere with analysis of study results;

9. Contraindication to any of the trial treatments (e.g. allergy to cow's milk protein).

• As assessed by the medical team on a case-by-case basis, but in general a clinically unstable state would include shock, hypothermia, hypoglycaemia or reduced conscious level.