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Transfer of Healthy Gut Flora for Restoration of Intestinal Microbiota Via Enema for Severe Acute Malnutrition (THRIVE)

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ClinicalTrials.gov Identifier: NCT03087097
Recruitment Status : Not yet recruiting
First Posted : March 22, 2017
Last Update Posted : November 20, 2018
Sponsor:
Collaborator:
University of Cape Town
Information provided by (Responsible Party):
Microbiome Health Research Institute

Brief Summary:

This single-center, randomized, double-blinded trial will compare the safety and efficacy of FMT given enema in subjects 18-60 months of age with uncomplicated, non-edematous SAM not responsive to standard therapy. Subjects must meet inclusion criteria, no exclusion criteria prior to randomization. Subjects will then be randomized by stratified random sampling (by age, diarrhea, MUAC and hyponatremia) in a 1:1 ratio at each site to 1 of 2 treatment groups:

  • FMT by enema: 10mL/kg (maximum 60mL) of donor fecal material will be infused.
  • Placebo by enema: 10mL/kg (maximum 60mL) of placebo material will be infused.

Subjects 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).

Stool samples will be collected at enrollment and through days 3, 7, 14, 21, 42 and 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 Transplant Biological: Placebo Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Estimated Study Start Date : December 3, 2018
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : May 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Fecal Microbiota Transplant
FMT by enema: 10mL/kg (maximum 150mL) of donor fecal material will be infused.
Biological: Fecal Microbiota Transplant
The investigational agent consists of screened-donor fecal material prepared for FMT. FMT will be administered using frozen screened-donor liquid stool (the investigational agent) in the form of enemas (60mL preparations) as per the published protocol in infants. 10mL/kg (maximum 60mL) of donor fecal material will be infused.

Placebo Comparator: Placebo
Placebo by enema: 10mL/kg (maximum 150mL) of placebo material will be infused.
Biological: Placebo
Placebo will be administered via enema as per delivery of FMT, using standardized placebo preparation. 10mL/kg (maximum 60mL) of placebo material will be infused.




Primary Outcome Measures :
  1. Safety of FMT compared to placebo delivered by enema [ Time Frame: 56 days ]
    Proportion of participants with a severe adverse event (SAE) grade 2 or above (according to NIH grading)


Secondary Outcome Measures :
  1. Stable engraftment of donor microbiota [ Time Frame: 56 days ]
    Stable engraftment will be defined with the Jensen-Shannon Divergence (JSD) between the bacteria community measured in the donor and recipient. Engraftment scores will be defined by the ratio between the JSD in comparison between the recipient and donor and the recipient and other healthy donors not providing material for their FMT.

  2. Normalization of leptin, a biomarker correlated with disease status and mortality in SAM [ Time Frame: 56 days ]
    Serology collected at baseline and end-line will be cryopreserved and analyzed by immunoassay for leptin, a biomarker predicting survival in SAM.



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Ages Eligible for Study:   18 Months to 60 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Subjects eligible to participate in this study must meet the following inclusion criteria:

  1. Age 18 to 60 months.
  2. Uncomplicated SAM defined as:

    • A WHZ of less than −3 according to the 2006 WHO Growth Standards or a mid-upper-arm circumference of less than 115 mm
    • No medical complications present
    • 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.
  3. No bilateral pitting pedal edema or generalized anasarca.
  4. HIV negative, exposed but negative or HIV positive on HAART with CD4 count > 500 cells/l.
  5. Optimal WHO treatment for uncomplicated SAM:

    • 7-day course of amoxicillin as part of standard therapy for uncomplicated SAM within the last 3 months.
    • Deworming in the last 3 months.
    • Micronutrient supplementation (Vitamin A, zinc and iron) as recommended by local guidelines.
    • Nutritional rehabilitation as recommended by local guidelines.
    • Written informed consent obtained by parent or caregiver.

Exclusion Criteria: Subjects will not be able to participate if they meet any of the following exclusion criteria:

  1. Evidence of complicated SAM, defined as any of the following:

    1. Signs of acute infection.
    2. One or more WHO Integrated Management of Childhood Illness danger signs.(2)
    3. Failure to pass appetite test.
    4. Presence of known comorbid diseases such as pulmonary Tuberculosis, cystic fibrosis, type I diabetes mellitus, intestinal malabsorptive syndromes, chronic lung disease, chronic liver disease, chronic renal disease or malignancy undergoing active chemotherapy.
    5. Bilateral pitting pedal edema or generalized anasarca
  2. Ongoing antibiotic use for indication other than SAM (e.g. infection, HIV prophylaxis).
  3. Congenital malformations, syndromic conditions and metabolic abnormalities (inborn errors of metabolism) that may adversely affect growth.
  4. Kwashiorkor or marasmic-kwashiorkor.
  5. Bilateral pitting edema Grade 2.
  6. Contraindications to enema:

    1. Anorectal malformations
    2. Rectal prolapse
    3. Hirschsprungs disease
    4. Other contraindication to enema.
  7. HIV positive children who are not on HAART or on HAART with a CD4 count <500 cells/l.
  8. Primary immune deficiencies
  9. Neutropenia
  10. Persistent and chronic diarrhea (>7 days of loose or water stools).
  11. Dysentery
  12. Intestinal abnormalities including malformations, Hirschsprungs disease and short bowel syndrome

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): NCT03087097


Contacts
Contact: Majdi Osman, MD MPH 617-575-2201 ext 712 majdi@openbiome.org

Sponsors and Collaborators
Microbiome Health Research Institute
University of Cape Town

Responsible Party: Microbiome Health Research Institute
ClinicalTrials.gov Identifier: NCT03087097     History of Changes
Other Study ID Numbers: THRIVE001
First Posted: March 22, 2017    Key Record Dates
Last Update Posted: November 20, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Malnutrition
Severe Acute Malnutrition
Nutrition Disorders