Therapeutic Approaches to Malnutrition Enteropathy (TAME)
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|ClinicalTrials.gov Identifier: NCT03716115|
Recruitment Status : Not yet recruiting
First Posted : October 23, 2018
Last Update Posted : October 23, 2018
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.
|Condition or disease||Intervention/treatment||Phase|
|Severe Acute Malnutrition||Dietary Supplement: Colostrum high protein powder (Neovite) Drug: N-Acetyl Glucosamine (GInNAC) Drug: Teduglutide Drug: Budesonide||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||235 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Therapeutic Approaches to Malnutrition Enteropathy: Phase II Trials of Four Novel Interventions in Children in Zambia and Zimbabwe|
|Estimated Study Start Date :||January 2019|
|Estimated Primary Completion Date :||September 2020|
|Estimated Study Completion Date :||September 2020|
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)
Bovine colostrum provided as powder will be reconstituted and administered orally or via NG tube.
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)
N-Acetyl glucosamine provided as powder will be reconstituted and administered orally or via NG tube.
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.
Teduglutide will be administered daily as subcutaneous injection
Budesonide 3mg orally daily for 14 days, then rapidly tapered, in addition to standard care following WHO guidelines for management of SAM.
Budesonide liquid (as marketed for nebulisation) will be administered orally or bia NG tube daily.
No Intervention: Standard care
Standard care following WHO guidelines for management of SAM.
- Composite measure of concentration of three faecal inflammatory markers [ Time Frame: 14-18 days ]Composite measure of concentration of three faecal inflammatory markers (myeloperoxidase, neopterin, alpha1-antitrypsin) measured by ELISA
- Lactulose:rhamnose ratio [ Time Frame: 14-18 days ]Lactulose:rhamnose ratio of concentration in urine samples collected over 2 hours following oral administration of test dose
- Plasma lipopolysaccharide (LPS) [ Time Frame: 14-18 days ]Plasma LPS concentration measured by limulus amoebacyte lysate assay
- Plasma biomarker lipopolysaccharide binding protein (LBP) [ Time Frame: 14-18 days ]Plasma LBP concentration measured by ELISA
- Plasma fatty acid binding protein (FABP) [ Time Frame: 14-18 days ]Plasma FABP concentration measured by ELISA
- Plasma soluble CD14 [ Time Frame: 14-18 days ]Plasma concentration of soluble CD14 measured by ELISA
- Plasma CD163 [ Time Frame: 14-18 days ]Plasma concentration of CD163 measured by ELISA
- Plasma CRP [ Time Frame: 14-18 days ]Plasma concentration of C-reactive protein measured by ELISA
- Plasma albumin [ Time Frame: 14-18 days ]Plasma concentration of albumin measured by ELISA
- Stool REG1-beta [ Time Frame: 14-18 days ]Stool concentration of REG-1 beta measured by ELISA
- Mortality [ Time Frame: 14 days and 28 days ]Number of deaths in each treatment allocation group
- Adverse events [ Time Frame: 14 days and 28 days ]Number of adverse events in each treatment allocation group
- Change in weight and length [ Time Frame: 14 days and 28 days ]Change in weight and length measured by experienced nurses and expressed as change in weight-for-length z score compared to WHO standard
- Days with diarrhoea [ Time Frame: 14-18 days ]Number of days during which diarrhoea was experienced assessed by experienced nurses
- Days with fever [ Time Frame: 14-18 days ]xv. Days with fever (two or more recordings of core temperature of 37.8oC or higher in any 24 h period)
- Villus height: crypt depth ratio [ Time Frame: 14-18 days ]Change in villus height and crypt depth measured in endoscopic biopsies (Lusaka only)
- Epithelial leakiness [ Time Frame: 14-18 days ]Leakage of fluorescein into gut lumen assessed by Watson score during confocal laser endomicroscopy (Lusaka only)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03716115
|Contact: Paul Kelly, MD||+260 966 firstname.lastname@example.org|
|Contact: Andrew Prendergast, PhD||+263 430 email@example.com|
|University Teaching Hospital, Nationalist Road|
|Harare Central Hospital|
|Study Chair:||Paul Kelly, MD||Queen Mary University of London|
|Principal Investigator:||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|