Therapeutic Approaches to Malnutrition Enteropathy

NCT03716115 | Completed Phase 2 DMC

• 1 other identifier: 011724 QM
• Study Type: interventional
• Target: 125
• Locations: 2 countries
• Sites: 3

Brief 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.

Conditions

Severe Acute Malnutrition

Outcome Measures

Primary Outcomes (1)

• Composite measure of concentration of three faecal inflammatory markers

  Composite measure of concentration of three faecal inflammatory markers (myeloperoxidase, neopterin, alpha1-antitrypsin) measured by ELISA

  14-18 days

Secondary Outcomes (16)

• Lactulose:rhamnose ratio

  14-18 days

• Plasma lipopolysaccharide (LPS)

  14-18 days

• Plasma biomarker lipopolysaccharide binding protein (LBP)

  14-18 days

• Plasma fatty acid binding protein (FABP)

  14-18 days

• Plasma soluble CD14

  14-18 days

Other Outcomes (4)

• Metabolomics

  14-18 days

• Transcriptomic analysis

  14-18 days

• Confocal laser endomicroscopy

  14-18 days

Study Arms (5)

Colostrum

EXPERIMENTAL

Colostrum high protein powder (Neovite) given orally or through NG tube 1.5g daily, in addition to standard care following WHO guidelines for management of SAM.

Dietary Supplement: Colostrum high protein powder (Neovite)

GInNAC

EXPERIMENTAL

N-Acetyl glucosamine (GInNAC). Given orally (1g three times daily) for 14 days, gradually increased from 0.5g to avoid osmotic diarrhoea, in addition to standard care following WHO guidelines for management of SAM.

Drug: N-Acetyl Glucosamine (GInNAC)

Teduglutide

EXPERIMENTAL

Teduglutide s/c. Administration by subcutaneous injection (0.5mg/kg/day) daily for 14 days, in addition to standard care following WHO guidelines for management of SAM.

Drug: Teduglutide

Budenoside

EXPERIMENTAL

Budesonide 3mg orally daily for 14 days, then rapidly tapered, in addition to standard care following WHO guidelines for management of SAM.

Drug: Budesonide

Standard care

NO INTERVENTION

Standard care following WHO guidelines for management of SAM.

Interventions

Colostrum high protein powder (Neovite) DIETARY_SUPPLEMENT

Bovine colostrum provided as powder will be reconstituted and administered orally or via NG tube.

Colostrum

N-Acetyl Glucosamine (GInNAC) DRUG

N-Acetyl glucosamine provided as powder will be reconstituted and administered orally or via NG tube.

GInNAC

Teduglutide DRUG

Teduglutide will be administered daily as subcutaneous injection

Teduglutide

Budesonide DRUG

Budesonide liquid (as marketed for nebulisation) will be administered orally or bia NG tube daily.

Budenoside

Eligibility Criteria

• Age: 6 Months - 59 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age 6 - 59 months, of either sex;
• Inpatient in the paediatric wards of one of the research sites;
• 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);
• Clinically stable\*;
• 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.

You may not qualify if:

• Clinically unstable\*;
• Less than 5kg body weight;
• Neurological disability which would explain or partly explain poor feeding;
• Oro-facial abnormalities which would explain or partly explain poor feeding;
• Caregiver unwilling to consent to child HIV testing;
• Haemoglobin concentration \< 6 g/dl at the time of enrolment;
• Caregiver unwilling to remain in hospital for the duration of the study treatment;
• 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;
• 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.

Sponsors & Collaborators

• Queen Mary University of London: lead

Study Sites (3)

University Teaching Hospital, Nationalist Road

Lusaka, Zambia

Location

Harare Central Hospital

Harare, Zimbabwe

Location

Parirenyatwa Hospital

Harare, Zimbabwe

Location

Related Publications (2)

• Chandwe K, Bwakura-Dangarembizi M, Amadi B, Tawodzera G, Ngosa D, Dzikiti A, Chulu N, Makuyana R, Zyambo K, Mutasa K, Mulenga C, Besa E, Sturgeon JP, Mudzingwa S, Simunyola B, Kazhila L, Zyambo M, Sonkwe H, Mutasa B, Chipunza M, Sauramba V, Langhaug L, Mudenda V, Murch SH, Hill S, Playford RJ, VanBuskirk K, Prendergast AJ, Kelly P. Malnutrition enteropathy in Zambian and Zimbabwean children with severe acute malnutrition: A multi-arm randomized phase II trial. Nat Commun. 2024 Apr 17;15(1):2910. doi: 10.1038/s41467-024-45528-0.

  PMID: 38632262 DERIVED

• Kelly P, Bell L, Amadi B, Bwakura-Dangarembizi M, VanBuskirk K, Chandwe K, Chipunza M, Ngosa D, Chulu N, Hill S, Murch S, Playford R, Prendergast A. TAME trial: a multi-arm phase II randomised trial of four novel interventions for malnutrition enteropathy in Zambia and Zimbabwe - a study protocol. BMJ Open. 2019 Nov 14;9(11):e027548. doi: 10.1136/bmjopen-2018-027548.

  PMID: 31727642 DERIVED

MeSH Terms

Conditions

Severe Acute Malnutrition

Interventions

Acetylglucosamine; teduglutide; Budesonide

Condition Hierarchy (Ancestors)

Malnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Glucosamine; Hexosamines; Amino Sugars; Carbohydrates; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Paul Kelly, MD

  Queen Mary University of London

  STUDY CHAIR

• Beatrice Amadi, MD

  University Teaching Hospital, Lusaka, Zambia

  PRINCIPAL INVESTIGATOR

• Andrew Prendergast, PhD

  Queen Mary University of London

  PRINCIPAL INVESTIGATOR

• Mutsa Bwakura-Dangarembizi, MB

  Parirenyatwa Hospital, Harare, Zimbabwe

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2018
• First Posted: October 23, 2018
• Study Start: May 4, 2020
• Primary Completion: April 27, 2021
• Study Completion: April 27, 2021
• Last Updated: September 27, 2021

Record last verified: 2018-09

Locations

ZA (1); ZI (2)