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Trial record 1 of 1 for:    fecal transplant | severe acute malnutrition
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Transfer of Healthy Gut Flora for Restoration of Intestinal Microbiota Via Enema for Patients in the Rehabilitative Phase of 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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03087097
Recruitment Status : Active, not recruiting
First Posted : March 22, 2017
Last Update Posted : April 15, 2020
Sponsor:
Collaborator:
University of Cape Town
Information provided by (Responsible Party):
Microbiome Health Research Institute

Tracking Information
First Submitted Date  ICMJE December 12, 2016
First Posted Date  ICMJE March 22, 2017
Last Update Posted Date April 15, 2020
Actual Study Start Date  ICMJE April 11, 2019
Estimated Primary Completion Date September 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 13, 2020)
Serious Adverse Events [ Time Frame: 56 days ]
Number of participants with an Adverse Event grade 2 or above up to 56 days post-treatment
Original Primary Outcome Measures  ICMJE
 (submitted: March 15, 2017)
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)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 13, 2020)
  • 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 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: [ 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 malnutrition. Stool biomarkers include Myeloperoxidase, Alpha-1-Antitrypsin, fecal calprotectin and neopterin. Serological biomarkers include CRP, endotoxin assay (Hek-Blue), and leptin.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 15, 2017)
  • 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.
  • 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Transfer of Healthy Gut Flora for Restoration of Intestinal Microbiota Via Enema for Patients in the Rehabilitative Phase of Malnutrition
Official Title  ICMJE Transfer of Healthy Gut Flora for Restoration of Intestinal Microbiota Via Enema (THRIVE) for Patients in the Rehabilitative Phase of Malnutrition: A Pilot Study Evaluating Microbial Engraftment, Safety and Nutritional Outcomes
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE
  • Severe Acute Malnutrition
  • Moderate Acute Malnutrition
Intervention  ICMJE Biological: Fecal 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.
Other Name: Microbiota transfer therapy (MTT)
Study Arms  ICMJE
  • Experimental: Fecal Microbiota Transplant
    FMT by enema: 10mL/kg (maximum 150mL) of healthy donor human intestinal microbiota will be infused.
    Intervention: Biological: Fecal Microbiota Transplantation
  • No Intervention: Standard of Care
    Standard of care treatment for malnutrition as prescribed by local and national Department of Health Guidelines
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: March 15, 2017)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2020
Estimated Primary Completion Date September 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 exclusion criteria:

  1. Evidence of current complicated malnutrition defined as any of the following:

    1. Admitted to acute care ward as inpatient
    2. Signs of severe acute infection such as pneumonia, bacteremia, meningitis. Minor infections such as candida dermatitis, pharyngitis, upper respiratory tract infections will be eligible for inclusion at the discretion of the study physician.
    3. One or more WHO Integrated Management of Childhood Illness danger signs.(3)
    4. Failure to pass appetite test.
    5. Presence of known comorbid diseases such as pulmonary Tuberculosis on treatment, cystic fibrosis, type I diabetes mellitus, intestinal malabsorptive syndromes, chronic lung disease, chronic liver disease, chronic renal disease, chronic neurological diseases (e.g. cerebral palsy) or malignancy undergoing active chemotherapy.
    6. Bilateral pitting pedal edema or generalized anasarca
  2. Have taken antibiotics in the past seven days before the Day 0 visit or are anticipated to need antibiotics up to seven days before the Day 0 visit.
  3. Congenital malformations, syndromic conditions, and congenital metabolic abnormalities (inborn errors of metabolism) that may adversely affect growth and in the view of the clinician, exposes the child to increased risk.

    a. Fetal alcohol syndrome (FAS) is not an exclusion.

  4. Presence of bilateral pitting edema Grade 2.
  5. Contraindications to rectal catheter enema:

    1. Anorectal malformations
    2. Rectal prolapse
    3. Hirschsprungs disease
    4. Other contraindication to enema.
  6. Primary immune deficiencies
  7. Acute, persistent or chronic diarrhea.
  8. Dysentery
  9. Intestinal abnormalities including malformations, Hirschsprungs disease and short bowel syndrome
  10. Any condition that the physician investigators deems unsafe, including other conditions or medications that the investigator determines puts the participant at greater risk from MTT
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Months to 60 Months   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE South Africa
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03087097
Other Study ID Numbers  ICMJE THRIVE001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Microbiome Health Research Institute
Study Sponsor  ICMJE Microbiome Health Research Institute
Collaborators  ICMJE University of Cape Town
Investigators  ICMJE
Principal Investigator: Majdi A Osman, MD MPH Microbiome Health Research Institute
Principal Investigator: Shrish Budree, MD MBChB DCH FCPeds Microbiome Health Research Institute
PRS Account Microbiome Health Research Institute
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP