Moderate Acute Malnutrition, Severe Acute Malnutrition
Conditions
Keywords
SAM, MAM
Brief summary
This single-center, randomized, open-label trial will compare the safety of MTT delivered by rectal catheter enema in participants 12-60 months of age with malnutrition (moderate acute malnutrition \[MAM\] or severe acute malnutrition \[SAM\]) who are in the rehabilitative phase of treatment and have failed to respond to at least 4 weeks of standard therapy. Participants must meet inclusion criteria, no exclusion criteria prior to randomization. Participants will then be randomized in a 1:1 ratio at each site to 1 of 2 treatment groups: * MTT by rectal catheter enema: 10mL/kg (maximum 150mL, +/- 5ml) of healthy donor human intestinal microbiota will be infused. * Standard of care treatment for malnutrition as prescribed by local and national Department of Health Guidelines Participants will be evaluated through 56 days (±3) after randomization for primary outcomes (safety) as well as secondary outcomes (nutritional, clinical and microbiological response). Participant blood and urine samples will be collected at enrollment and day 56. Participant stool samples will be collected at enrollment and through days 3, 7, 21 and 56, thereafter, 3 months, 4 months, and 6 months. A caregiver stool sample will be collected at enrollment and day 56. Samples will be used for microbiome determination and other exploratory microbiological endpoints. An aliquot of donor stool will also be stored for microbiome determination and other exploratory microbiological endpoints and assessment of newly acquired infectious agents.
Interventions
BIOLOGICALFecal Microbiota Transplantation
Fecal microbiota delivered by rectal catheter enema in participants 12-60 months of age with malnutrition (MAM or SAM) who are in the rehabilitation phase of treatment and have failed to respond to at least 4 weeks of standard therapy.
Sponsors
University of Cape Town
Microbiome Health Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Months to 60 Months
Healthy volunteers
No
Inclusion criteria
Participant Inclusion Criteria Participants eligible to participate in this study must meet the following inclusion criteria: 1. Age 12 to 60 months. 2. Current diagnosis of malnutrition (defined as a WHZ less than -2 according to the WHO 2006 standards or a MUAC less than 125mm) with failure to respond nutritionally, defined as: a. A WHZ of less than -2 according or a mid-upper-arm circumference of less than 125 mm i. No medical complications present ii. Participant is sufficiently alert and successfully passes the appetite test which involves consumption of breastmilk or a ready to use therapeutic food (RUTF) under supervision. iii. Participant is in the rehabilitation phase of treatment for malnutrition 3. HIV negative 4. Received at last four weeks of optimal WHO treatment for malnutrition: 1. Micronutrient supplementation (Vitamin A, zinc and iron) as recommended by local guidelines 2. Nutritional rehabilitation as recommended by local guidelines. 5. Written informed consent obtained by parent or caregiver. Participant
Exclusion criteria
Participants will not be able to participate if they meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serious Adverse Events | 56 days | Number of participants with an Adverse Event grade 2 or above up to 56 days post-treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Nutritional recovery: | 56 days | Proportion of participants with nutritional recovery at day 56 after randomization. Defined as weight for height z-score (WHZ) ≥ -2 or MUAC ≥ 125 mm. In cases where there is a significant discrepancy between the weight and MUAC the participants weight will be used as the definitive measure. |
| Clinical: | 56 days | Presence of signs and symptoms or complications of acute malnutrition. Clinical signs include fever (axillary temperature \> 38.5⁰C), tachypnea (average of two measures; defined as respiratory rate of \> 40 breaths per minute for children 12-60 months of age). Symptoms include diarrhea (≥ 3 loose stools in the last 24 hours), vomiting, and cough. |
| Microbiological: | 56 Days | Assess engraftment of donor microbial communities in recipients through taxonomic characterization of donor and recipient microbiota pre- and post-MTT using both 16S rRNA and metagenomic techniques. |
| Translational: | 56 Days | Assess the capacity for MTT to normalize biomarkers correlated with disease status and mortality in malnutrition. Stool biomarkers include Myeloperoxidase, Alpha-1-Antitrypsin, fecal calprotectin and neopterin. Serological biomarkers include CRP, endotoxin assay (Hek-Blue), and leptin. |
Countries
South Africa
Outcome results
None listed