Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Therapeutic Approaches to Malnutrition Enteropathy (TAME)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03716115
Recruitment Status : Not yet recruiting
First Posted : October 23, 2018
Last Update Posted : October 23, 2018
Sponsor:
Information provided by (Responsible Party):
Queen Mary University of London

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.


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

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 235 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malnutrition
Drug Information available for: Teduglutide

Arm Intervention/treatment
Experimental: Colostrum
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.

Experimental: GInNAC
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.

Experimental: Teduglutide
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
Teduglutide will be administered daily as subcutaneous injection

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



Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. Plasma lipopolysaccharide (LPS) [ Time Frame: 14-18 days ]
    Plasma LPS concentration measured by limulus amoebacyte lysate assay

  3. Plasma biomarker lipopolysaccharide binding protein (LBP) [ Time Frame: 14-18 days ]
    Plasma LBP concentration measured by ELISA

  4. Plasma fatty acid binding protein (FABP) [ Time Frame: 14-18 days ]
    Plasma FABP concentration measured by ELISA

  5. Plasma soluble CD14 [ Time Frame: 14-18 days ]
    Plasma concentration of soluble CD14 measured by ELISA

  6. Plasma CD163 [ Time Frame: 14-18 days ]
    Plasma concentration of CD163 measured by ELISA

  7. Plasma CRP [ Time Frame: 14-18 days ]
    Plasma concentration of C-reactive protein measured by ELISA

  8. Plasma albumin [ Time Frame: 14-18 days ]
    Plasma concentration of albumin measured by ELISA

  9. Stool REG1-beta [ Time Frame: 14-18 days ]
    Stool concentration of REG-1 beta measured by ELISA

  10. Mortality [ Time Frame: 14 days and 28 days ]
    Number of deaths in each treatment allocation group

  11. Adverse events [ Time Frame: 14 days and 28 days ]
    Number of adverse events in each treatment allocation group

  12. 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

  13. Days with diarrhoea [ Time Frame: 14-18 days ]
    Number of days during which diarrhoea was experienced assessed by experienced nurses

  14. 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)

  15. Villus height: crypt depth ratio [ Time Frame: 14-18 days ]
    Change in villus height and crypt depth measured in endoscopic biopsies (Lusaka only)

  16. Epithelial leakiness [ Time Frame: 14-18 days ]
    Leakage of fluorescein into gut lumen assessed by Watson score during confocal laser endomicroscopy (Lusaka only)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   6 Months to 59 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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. Within 72 hours of initiation of transition (from F75 feed to F100 or RUTF);
  5. Clinically stable*;
  6. 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.

Information from the National Library of Medicine

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


Contacts
Layout table for location contacts
Contact: Paul Kelly, MD +260 966 751875 m.p.kelly@qmul.ac.uk
Contact: Andrew Prendergast, PhD +263 430 6028 a.prendergast@qmul.ac.uk

Locations
Layout table for location information
Zambia
University Teaching Hospital, Nationalist Road
Lusaka, Zambia
Zimbabwe
Harare Central Hospital
Harare, Zimbabwe
Parirenyatwa Hospital
Harare, Zimbabwe
Sponsors and Collaborators
Queen Mary University of London
Investigators
Layout table for investigator information
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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Queen Mary University of London
ClinicalTrials.gov Identifier: NCT03716115    
Other Study ID Numbers: 011724 QM
First Posted: October 23, 2018    Key Record Dates
Last Update Posted: October 23, 2018
Last Verified: September 2018

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Malnutrition
Severe Acute Malnutrition
Nutrition Disorders
Budesonide
Teduglutide
Anti-Inflammatory Agents
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Gastrointestinal Agents
Radiation-Protective Agents
Protective Agents