Transfer of Healthy Gut Flora for Restoration of Intestinal Microbiota Via Enema for Severe Acute Malnutrition (THRIVE)
|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: NCT03087097|
Recruitment Status : Recruiting
First Posted : March 22, 2017
Last Update Posted : July 19, 2019
This single-center, randomized, open-label trial will compare the safety and efficacy of MTT delivered by rectal catheter enema in participants 12-60 months of age with stable SAM not responsive to at least 8 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 SAM as prescribed by local and national Department of Health Guidelines Participants will be evaluated through 56 days (±5) after randomization for primary outcomes (safety) as well as secondary outcomes (nutritional, clinical and microbiological response). See definition under endpoints/outcome measures above.
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. 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.
|Condition or disease||Intervention/treatment||Phase|
|Severe Acute Malnutrition||Biological: Fecal Microbiota Transplantation||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||None (Open Label)|
|Official Title:||Transfer of Healthy Gut Flora for Restoration of Intestinal Microbiota Via Enema (THRIVE) for Severe Acute Malnutrition: A Pilot Study Evaluating Microbial Engraftment, Safety and Nutritional Outcomes|
|Actual Study Start Date :||January 14, 2019|
|Estimated Primary Completion Date :||December 2019|
|Estimated Study Completion Date :||May 2020|
Experimental: Fecal Microbiota Transplant
FMT by enema: 10mL/kg (maximum 150mL) of donor fecal material will be infused.
Biological: Fecal Microbiota Transplantation
Fecal microbiota delivered by rectal catheter enema in participants 12-60 months of age with stable SAM not responsive to at least 8 weeks of standard therapy.
No Intervention: Standard of Care
Standard of care treatment for SAM as prescribed by local and national Department of Health Guidelines
- SAEs [ Time Frame: 56 days ]Proportion of participants with a severe adverse event (SAE) grade 2 or above (according to NIH grading)
- Nutritional recovery: [ Time Frame: 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: [ Time Frame: 56 days ]Presence of signs and symptoms or complications of SAM at day 56. 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: [ Time Frame: 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: [ Time Frame: 56 Days ]Assess the capacity for MTT to normalize biomarkers correlated with disease status and mortality in SAM. Stool biomarkers include Myeloperoxidase, Alpha-1-Antitrypsin, fecal calprotectin and neopterin. Serological biomarkers include CRP, endotoxin assay (Hek-Blue), IGF1, Ferritin and leptin.
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): NCT03087097
|Contact: Susie Corl, MPH, CIP, CCRP, CHRC||617-575-2201 ext firstname.lastname@example.org|
|Contact: Mary Njenga||617-575-2201 ext email@example.com|
|University of Cape Town||Recruiting|
|Cape Town, South Africa|
|Contact: Sandhia Padayachee, MD firstname.lastname@example.org|
|Principal Investigator: Heather Zar, MD|
|Principal Investigator:||Majdi A Osman, MD MPH||Microbiome Health Research Institute|
|Principal Investigator:||Shrish Budree, MD MBChB DCH FCPeds||Microbiome Health Research Institute|